Radbound University

Nijmegen, Netherlands

Radbound University

Nijmegen, Netherlands

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Woudenberg J.,University of Groningen | Woudenberg J.,Radbound University | Rembacz K.P.,University of Groningen | Van Den Heuvel F.A.J.,University of Groningen | And 10 more authors.
Hepatology | Year: 2010

Caveolae are a subtype of cholesterol-enriched lipid microdomains/rafts that are routinely detected as vesicles pinching off from the plasma membrane. Caveolin-1 is an essential component of caveolae. Hepatic caveolin-1 plays an important role in liver regeneration and lipid metabolism. Expression of caveolin-1 in hepatocytes is relatively low, and it has been suggested to also reside at other subcellular locations than the plasma membrane. Recently, we found that the peroxisomal membrane contains lipid microdomains. Like caveolin-1, hepatic peroxisomes are involved in lipid metabolism. Here, we analyzed the subcellular location of caveolin-1 in rat hepatocytes. The subcellular location of rat hepatocyte caveolin-1 was analyzed by cell fractionation procedures, immunofluorescence, and immunoelectron microscopy. Green fluorescent protein (GFP)-tagged caveolin-1 was expressed in rat hepatocytes. Lipid rafts were characterized after Triton X-100 or Lubrol WX extraction of purified peroxisomes. Fenofibric acid-dependent regulation of caveolin-1 was analyzed. Peroxisome biogenesis was studied in rat hepatocytes after RNA interference-mediated silencing of caveolin-1 and caveolin-1 knockout mice. Cell fractionation and microscopic analyses reveal that caveolin-1 colocalizes with peroxisomal marker proteins (catalase, the 70 kDa peroxisomal membrane protein PMP70, the adrenoleukodystrophy protein ALDP, Pex14p, and the bile acid-coenzyme A:amino acid N-acyltransferase BAAT) in rat hepatocytes. Artificially expressed GFP-caveolin-1 accumulated in catalase-positive organelles. Peroxisomal caveolin-1 is associated with detergent-resistant microdomains. Caveolin-1 expression is strongly repressed by the peroxisome proliferator-activated receptor-α agonist fenofibric acid. Targeting of peroxisomal matrix proteinsandperoxisomenumberandshape were not altered in rat hepatocytes with 70%-80% reduced caveolin-1 levels and in livers of caveolin-1 knockout mice. Conclusion: Caveolin-1 is enriched in peroxisomes of hepatocytes. Caveolin-1 is not required for peroxisome biogenesis, but this unique subcellular location may determine its important role in hepatocyte proliferation and lipid metabolism. Copyright © 2009 by the American Association for the Study of Liver Diseases.


Eek A.,Radbound University | Oyen W.J.G.,Radbound University | Nagtegaal I.D.,Radbound University | Boerman O.C.,Radbound University
Annals of Surgery | Year: 2011

Objective: The aim of this study was to test the hypothesis that adjuvant radioimmunotherapy (RIT) prevents recurrent liver metastases and/or results in improved survival after tumorectomy in an experimental model. Background: Although partial hepatectomy can improve 5-year survival of patients with colorectal liver metastases up to 58%, recurrent tumor growth in the liver occurs frequently. Radioimmunotherapy using radiolabeled monoclonal antibodies directed against tumor-associated antigens is considered most suited for treating minimal residual disease and could therefore serve as an adjuvant after surgery. Methods: Liver metastases were induced in male Wag/Rij rats by a minilaparotomy with intrahepatic injection of 0.3 × 10 6 CC531 tumor cells. The biodistribution of the radiolabeled monoclonal antibody MG1, directed against a 80-kDa cell surface antigen on CC531 tumors, in this model was determined at 1, 3, and 7 days after intravenous administration. The therapeutic efficacy of 177Lu-MG1 was compared with that of a sham antibody (UPC10), labeled with the same activity dose of Lu-177, and saline only. Radioimmunotherapy was administered either at the day of the tumorectomy (day 14 after tumor cell inoculation) or 7 days later. Primary endpoint was survival. Results: Radiolabeled MG1 preferentially accumulated in tumor lesions in the liver reaching a maximum 3 days postinjection (8.7 ± 0.6% injected dose per gram). Both the administration 177Lu-MG1 and 177Lu-UPC10 resulted in a transient decrease in body weight. No other signs of clinical discomfort were registered. The survival curves of the group that received 177Lu-UPC10 and the group that received saline only did not differ (P=0.886).Administration of RIT immediately after surgery improved survival compared to administration of the control antibody (hazard ratio [HR], 1.54; P = 0.051), which was even more pronounced when survival was adjusted for the weight of the resected tumor (HR, 1.71; P = 0.027). A therapeutic efficacy of delayed treatment seemed likely (HR, 2.34; P = 0.055). Survival after early administration did not differ from delayed administration (HR, 1.16; P = 0.763). Conclusion: This study provides proof of principle that RIT can be an effective adjuvant treatment modality after surgical treatment of colorectal liver metastases. Copyright © 2011 by Lippincott Williams & Wilkins.


Zarei M.,Institute for Cognitive science Studies | Beckmann C.F.,Radbound University | Binnewijzend M.A.A.,Radiology and Image Analysis Center | Schoonheim M.M.,Radiology and Image Analysis Center | And 4 more authors.
NeuroImage | Year: 2013

In this study we segment the hippocampus according to functional connectivity assessed from resting state functional magnetic resonance images in healthy subjects and in patients with Alzheimer's disease (AD).We recorded the resting FMRI signal from 16 patients and 22 controls. We used seed-based functional correlation analyses to calculate partial correlations of all voxels in the hippocampus relative to characteristic regional signal changes in the thalamus, the prefrontal cortex (PFC) and the posterior cingulate cortex (PCC), while controlling for ventricular CSF and white matter signals. Group comparisons were carried out controlling for age, gender, hippocampal volume and brain volume. The strength of functional connectivity in each region also was correlated with neuropsychological measures.We found that the hippocampus can be segmented into three distinct functional subregions (head, body, and tail), according to the relative connectivity with PFC, PCC and thalamus, respectively. The AD group showed stronger hippocampus-PFC and weaker hippocampus-PCC functional connectivity, the magnitudes of which correlated with MMSE in both cases.The results are consistent with an adaptive role of the PFC in the context of progression of dysfunction in PCC during earlier stages of AD. Extension of our approach could integrate regional volume measures for the hippocampus with their functional connectivity patterns in ways that should increase sensitivity for assessment of AD onset and progression. © 2012 Elsevier Inc.


Miller M.A.,SUNY Upstate Medical University | Race A.,SUNY Upstate Medical University | Waanders D.,Radbound University | Cleary R.,Bentley University | And 4 more authors.
Journal of the Mechanical Behavior of Biomedical Materials | Year: 2011

Maintaining adequate fixation between cement and bone is important for successful long term survival of cemented total joint replacements. Mixed-mode loading conditions (combination of tension/compression and shear) are present during in vivo loading, but the micromotion response of the interface to these conditions is not fully understood.Non-destructive, multi-axial loading experiments were conducted on laboratory prepared (n=6) and postmortem (n=6) human cement-bone interfaces. Specimens were mounted in custom loading discs and loaded at 0°, 30°, 60°, and 90° relative to the interface plane where 0° represents normal loading to the interface, and 90° represents shear loading along the longitudinal axis of the femur. Axial compliance did not depend on loading angle for laboratory prepared (p=0.96) or postmortem specimens (p=0.62). The cement-bone interface was more compliant under tensile than compressive loading at the 0° loading angle only (p=0.024). The coupled transverse to axial compliance ratio, which is a measure of the coupled motion, was small for laboratory prepared (0.115 ± 0.115) and postmortem specimens (0.142 ± 0.101). There was a moderately strong inverse relationship between interface compliance and contact index (r 2=0.65).From a computational modeling perspective, the results of the current study support the concept that the cement-bone interface could be numerically implemented as a compliant layer with the same initial stiffness in tension and shear directions. The magnitude of the compliance could be modified to simulate immediate post-operative conditions (using laboratory prepared data set) or long-term remodeling (using postmortem data set). © 2010 Elsevier Ltd.


Soler J.K.,University of Ulster | Soler J.K.,Mediterranean Institute of Primary Care | Okkes I.,Mediterranean Institute of Primary Care | Okkes I.,University of Amsterdam | And 7 more authors.
Family Practice | Year: 2012

Introduction: This is a study of the epidemiology of family medicine (FM) in three practice populations from the Netherlands, Malta and Serbia. Incidence and prevalence rates, especially of reasons for encounter (RfEs) and episode labels, are compared. Methodology: Participating family doctors (FDs) recorded details of all their patient contacts in an episode of care (EoC) structure using electronic patient records based on the International Classification of Primary Care (ICPC), collecting data on all elements of the doctor-patient encounter. RfEs presented by the patient, all FD interventions and the diagnostic labels (EoCs labels) recorded for each encounter were classified with ICPC (ICPC-2-E in Malta and Serbia and ICPC-1 in the Netherlands). Results: The content of family practice in the three population databases, incidence and prevalence rates of the common top 20 RfEs and EoCs in the three databases are given. Conclusions: Data that are collected with an episode-based model define incidence and prevalence rates much more precisely. Incidence and prevalence rates reflect the content of the doctor- patient encounter in FM but only from a superficial perspective. However, we found evidence of an international FM core content and a local FM content reflected by important similarities in such distributions. FM is a complex discipline, and the reduction of the content of a consultation into one or more medical diagnoses, ignoring the patient's RfE, is a coarse reduction, which lacks power to fully characterize a population's health care needs. In fact, RfE distributions seem to be more consistent between populations than distributions of EoCs are, in many respects. © The Author 2012. Published by Oxford University Press. All rights reserved.


Janssens A.,Radbound University | Pelzer B.,Radboud University Nijmegen
Biodemography and Social Biology | Year: 2012

Prior research has suggested that the quality of maternal care given to infants and small children plays an important role in the strong clustering of children's deaths. In this article, we investigate the quality of maternal care provided by those women who most nineteenth-century social commentators declared would never make good housewives or mothers: the young girls and women working in textile mills. We carried out this examination using an analysis of children's mortality risks in two textile cities in The Netherlands between roughly 1900 and 1930. Our analysis suggests that these children's clustered mortality risks cannot have resulted from either their mothers' labor market experience or biological or genetic factors. © 2012 Copyright Society for Biodemography and Social Biology.


PubMed | Afdeling Zorgondersteuning en Behandeling, Radboud University Nijmegen and Radbound University
Type: Journal Article | Journal: Journal of intellectual disability research : JIDR | Year: 2016

Students without intellectual disability (ID) start experimenting with tobacco and alcohol between 12 and 15years of age. However, data for 12- to 15-year old students with ID are unavailable. Prevention programs, like PREPARED ON TIME (based on the attitude-social influence-efficacy model), are successful, but their efficacy has not been studied in students with ID. The objectives of this study were (1) to undertake a cluster randomised control trial to test the efficacy of the e-learning program among 12- to 15-year old students with mild and borderline ID in secondary special-needs schools and (2) to examine the tobacco and alcohol use for this population.Five schools, randomly selected to be part of either the experimental group or the control group, participated in this study. Passive informed consent was used in which parents and their children can refuse to participate in the study, resulting in 111 students in the experimental group and 143 students in the control group. A total of 210 students completed both baseline and follow-up questionnaires. Primary outcome variables are the knowledge and attitude towards alcohol and tobacco use. This study is registered in the ISRCTN registry with number ISRCTN95279686.Baseline findings showed that a large proportion of all respondents had initiated smoking (49%) and drinking (75%), well above the expected numbers based on national figures. PREPARED ON TIME did not affect the behavioural determinants (i.e. attitude, subjective norm and self-efficacy), except modelling on smoking. Additionally, alcohol-related knowledge of students in the experimental group increased after the completion of the program.To obtain effective results on behavioural outcomes from PREPARED ON TIME, a greater degree of flexibility (i.e. repetition, extension of the program, role playing, etc.) is required. Furthermore, prevention needs to be implemented at a younger age, as 6% of the students tried their first cigarette and 15% of the students drank alcohol at the age of 10years or younger.


Sim M.,University of Western Australia | Dawson B.,University of Western Australia | Landers G.,University of Western Australia | Wiegerinck E.T.,Radbound University | And 5 more authors.
European Journal of Applied Physiology | Year: 2012

The eVect of carbohydrate (CHO) consumption during prolonged endurance running on post-exercise inXammation and hepcidin levels was investigated. Eleven well-trained male endurance athletes completed a graded exercise test, followed by two experimental running trials in a randomized order. The two experimental trials consisted of a 90 min run at 75% of the peak oxygen uptake velocity (vVO 2peak), while consuming a solution with either 6% CHO or a placebo (PLA) equivalent at 3 ml kg1 every 20 min. Serum interleukin-6 (IL-6), free hemoglobin (Hb), haptoglobin (Hp), hepcidin and iron parameters were assessed throughout the post-run recovery period. Serum iron and IL-6 were signiWcantly elevated immediately postrun in both CHO and PLA (p≤0.05), with no diVerences between trials. Serum-free Hb increased and Hp decreased signiWcantly immediately post-run in both conditions (p≤ 0.05). Serum soluble transferrin receptor levels were signiWcantly below the baseline at 3 and 24 h post-run in both conditions (p≤ 0.05). Serum hepcidin concentration recorded 3 h post-run in both conditions was signiWcantly elevated (p ≤ 0.05), and had returned to the baseline by 24 h post-run (p≤ 0.05). The use of a 6% CHO solution at 3 ml kg -1 20 min -1 during endurance running did not attenuate the inXammatory response and subsequent increase in serum hepcidin levels during the post-run recovery period.© 2011 Springer-Verlag.


Chiesa A.,University of Bologna | Chiesa A.,Messina University | Castagner V.,University of Bologna | Andrisano C.,University of Bologna | And 4 more authors.
Psychiatry Research | Year: 2015

Mindfulness-based cognitive therapy (MBCT) showed efficacy for currently depressed patients. However, most of the available studies suffer from important methodological shortcomings, including the lack of adequate control groups. The present study aims to compare MBCT with a psycho-educational control group designed to be structurally equivalent to the MBCT program but excluding the main putative "active ingredient" of MBCT (i.e., mindfulness meditation practice) for the treatment of patients with major depression (MD) who did not achieve remission following at least 8 weeks of antidepressant treatment. Out of 106 screened subjects, 43 were randomized to receive MBCT or psycho-education and were prospectively followed for 26 weeks. MD severity was assessed with the Hamilton Rating Scale for Depression (HAM-D) and the Beck Depression Inventory-II (BDI-II). Measures of anxiety, mindfulness, and quality of life were also included. All assessments were performed at baseline, 4, 8, 17 and 26-weeks. Both HAM-D and BDI scores, as well as quality of life and mindfulness scores, showed higher improvements, which were particularly evident over the long-term period, in the MBCT group than in the psycho-education group. Although limited by a small sample size, the results of this study suggest the superiority of MBCT over psycho-education for non-remitted MD subjects. © 2015 Elsevier Ireland Ltd.


(Phys.org)—Several properties of the extracellular matrix affect cellular interaction, including stem cell differentiation. Some of these are physical properties, such as topography and matrix stiffness. In an effort to investigate these physical properties, Rajat K. Das, Veronika Gocheva, Roel Hammink, Omar F. Zouani, and Alan E. Rowan from Radbound University in The Netherlands, and the company Histide in Switzerland designed a model 3D hydrogel polymer system that demonstrates how stress-stiffening in the extracellular matrix causes human mesenchymal stem cells to favor osteogenesis over adipogenesis. Using their new model system, they determined that the expression of DCAMKL1, a microtubule associated protein, is decreasing when stress-stiffness is higher, demonstrating a novel pathway in which microtubule dynamics affects cell fate. Their work appears in Nature Materials.

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