University Ziekenhuizen

Leuven, Belgium

University Ziekenhuizen

Leuven, Belgium
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Salta E.,Vlaams Instituut voor Biotechnologie Center for Brain and Disease | Salta E.,University Ziekenhuizen | De Strooper B.,Vlaams Instituut voor Biotechnologie Center for Brain and Disease | De Strooper B.,University Ziekenhuizen | De Strooper B.,University College London
FASEB Journal | Year: 2017

With the consideration of the broad involvement ofmicroRNAs (miRNAs) in the regulation ofmolecular networks in the brain, it is not surprising thatmiRNA dysregulation causes neurodegeneration in animalmodels. miRNA profiling in the human brain has revealedmiR-132 as one of the most severely down-regulatedmiRNAs at the intermediate and late Braak stages ofAlzheimer's disease (AD), aswell as in other neurodegenerative disorders. Suppression ofmiR-132 aggravates multiple layers of pathology at the molecular and functional level.We describe the potential therapeutic implications of these findings and suggest miRNA targeting or replacement as a realistic multi-hit, therapeutic strategy for AD. Salta, E., De Strooper, B.microRNA-132: a key noncoding RNA operating in the cellular phase of Alzheimer's disease. FASEB J. 31, 424-433 (2017). © FASEB.

D'Hooghe M.B.,National Center for Multiple Sclerosis | Haentjens P.,Vrije Universiteit Brussel | Nagels G.,National Center for Multiple Sclerosis | Nagels G.,University of Mons | And 3 more authors.
Multiple Sclerosis Journal | Year: 2012

Background: Sunlight and vitamin D have been inversely associated with the risk of multiple sclerosis (MS).Objective: We investigated sunlight exposure and sun sensitivity in relation to disability progression in MS.Methods: We conducted a survey among persons with MS, registered by the Flemish MS society, Belgium, and stratified data according to relapsing-onset and progressive-onset MS. We used Kaplan-Meier survival and Cox proportional hazard regression analyses with time to Expanded Disability Status Scale (EDSS) 6 as outcome measure. Hazard ratios for the time from onset and from birth were calculated for the potentially predictive variables, adjusting for age at onset, gender and immunomodulatory treatment.Results: 704 (51.3%) of the 1372 respondents had reached EDSS 6. In relapsing-onset MS, respondents reporting equal or higher levels of sun exposure than persons of the same age in the last 10 years had a decreased risk of reaching EDSS 6. In progressive-onset MS, increased sun sensitivity was associated with an increased hazard of reaching EDSS 6.Conclusion: The association of higher sun exposure with a better outcome in relapsing-onset MS may be explained by either a protective effect or reverse causality. Mechanisms underlying sun sensitivity might influence progression in progressive-onset MS. © The Author(s) 2012.

PubMed | St Marks Hospital, University Ziekenhuizen, Sourasky Medical Center, Academisch Medisch Centrum and 2 more.
Type: | Journal: Journal of Crohn's & colitis | Year: 2016

Restorative proctocolectomy in elderly inflammatory bowel disease [ IBD] patients is controversial and limited data are available on the outcomes of surgery. The aim of this study was to evaluate the safety, efficacy, and long-term results of ileal-pouch-anal anastomosis in elderly patients, in a multicentre survey from European referral centres.The International Pouch Database [IPD] combined 101 variables. Patients aged 65 years were matched on the basis of open versus laparoscopic surgery with a control group of consecutive younger unselected patients with a ratio of 1:2. Statistical analysis was performed using two-tailed t test, chi square and Fishers exact tests, Kaplan-Meier function, and log-rank tests where appropriate.In the IPD, 77 patients aged 65 years [Group A] and 154 control patients [Group B] were identified. Elderly patients had more comorbidities [p = 0.0001], longer disease duration [p = 0.001], less extensive disease [p = 0.006], more previous abdominal operations [p = 0.0006], surgery for cancer or dysplasia more frequently [p = 0.0001], fewer single-stage procedures [p = 0.03], more diversions after ileal pouch-anal anastomosis [IPAA] [p = 0.05], and a higher laparoscopic conversion rate [p = 0.04]. Postoperative complications and pouch failure were similar between the groups, but Group A had more Clavien-Dindo IV-V complications [p = 0.04], and longer length of stay [p = 0.007]. Laparoscopy was associated with a shorter duration of surgery [p = 0.0001], and length of stay [p = 0.0001], and the same complication rate as open surgery.Restorative proctocolectomy can be performed in selected elderly patients, but there is a higher risk of postoperative complications and longer length of stay in this group. Laparoscopy is associated with shorter operating time and length of stay.

Ottoni C.,University Ziekenhuizen | Ottoni C.,Catholic University of Leuven | Ricaut F.-X.,French National Center for Scientific Research | Vanderheyden N.,University Ziekenhuizen | And 4 more authors.
European Journal of Human Genetics | Year: 2011

The archaeological site of Sagalassos is located in Southwest Turkey, in the western part of the Taurus mountain range. Human occupation of its territory is attested from the late 12th millennium BP up to the 13th century AD. By analysing the mtDNA variation in 85 skeletons from Sagalassos dated to the 11th-13th century AD, this study attempts to reconstruct the genetic signature potentially left in this region of Anatolia by the many civilizations, which succeeded one another over the centuries until the mid-Byzantine period (13th century BC). Authentic ancient DNA data were determined from the control region and some SNPs in the coding region of the mtDNA in 53 individuals. Comparative analyses with up to 157 modern populations allowed us to reconstruct the origin of the mid-Byzantine people still dwelling in dispersed hamlets in Sagalassos, and to detect the maternal contribution of their potential ancestors. By integrating the genetic data with historical and archaeological information, we were able to attest in Sagalassos a significant maternal genetic signature of Balkan/Greek populations, as well as ancient Persians and populations from the Italian peninsula. Some contribution from the Levant has been also detected, whereas no contribution from Central Asian population could be ascertained. © 2011 Macmillan Publishers Limited.

Degryse S.,Vlaams Instituut voor Biotechnologie Center for the Biology of the Disease | Degryse S.,Katholieke University Leuven Center for Human Genetics | De Bock C.E.,Vlaams Instituut voor Biotechnologie Center for the Biology of the Disease | De Bock C.E.,Katholieke University Leuven Center for Human Genetics | And 21 more authors.
Blood | Year: 2014

JAK3 is a tyrosine kinase that associates with the common g chain of cytokine receptors and is recurrently mutated in T-cell acute lymphoblastic leukemia (T-ALL). We tested the transforming propertiesofJAK3 pseudokinase and kinase domain mutants usinginvitro and in vivo assays. Most, but not all, JAK3 mutants transformed cytokine-dependent Ba/F3 or MOHITO cell lines to cytokine-independent proliferation. JAK3 pseudokinase mutants were dependent on Jak1 kinase activity for cellular transformation, whereas the JAK3 kinase domain mutant could transform cellsinaJak1 kinase-independent manner. Reconstitution of the IL7 receptor signaling complex in 293T cells showed that JAK3 mutants required receptor bindingtomediate downstream STAT5 phosphorylation. Mice transplanted with bone marrow progenitor cells expressing JAK3 mutants developed a long-latency transplantable T-ALL-like disease, characterized by an accumulation of immature CD8+ T cells. In vivo treatment of leukemic mice with the JAK3 selective inhibitor tofacitinib reduced the white blood cell count and caused leukemic cell apoptosis. Our data show that JAK3 mutations are drivers of T-ALL and require the cytokine receptor complex for transformation. These results warrant further investigation of JAK1/JAK3 inhibitors for the treatment of T-ALL. © 2014 by The American Society of Hematology.

Reymen B.,University Ziekenhuizen | Spiessens S.,University Ziekenhuizen | Lievens Y.,University Ziekenhuizen
Radiotherapy and Oncology | Year: 2010

This planning study in Hodgkin's disease confirmed smaller irradiated volumes and subsequently lower doses to lungs, heart and breasts for involved node radiotherapy compared to involved field irradiation. However, shifting the arms from alongside the body to above the head offsets the observed benefit on dose to heart and breasts. © 2010 Elsevier Ireland Ltd. All rights reserved.

Rayyan M.,University Hospitals | Rayyan M.,University Ziekenhuizen | Devlieger H.,University Hospitals | Jochum F.,Zentrum fur Neonatologie und Padiatrische Intensivmedizin | And 2 more authors.
Journal of Parenteral and Enteral Nutrition | Year: 2012

Background: For premature neonates needing parenteral nutrition (PN), a balanced lipid supply is crucial. The authors hypothesized that a lipid emulsion containing medium-chain triglycerides (MCTs) and soybean, olive, and fish oils would be as safe and well tolerated as a soybean emulsion while beneficially influencing the fatty acid profile. Methods: Double-blind, controlled study in 53 neonates (<34 weeks' gestation) randomized to receive at least 7 days of PN containing either an emulsion of MCTs and soybean, olive, and fish oils or a soybean oil emulsion. Target lipid dosage was 1.0 g fat/kg body weight [BW]/d on days 1-3, 2 g/kg BW/d on day 4, 3 g/kg BW/d on day 5, and 3.5 g/kg BW/d on days 6-14. Results: Test emulsion vs control, mean ± SD: baseline triglyceride concentrations were 0.52 ± 0.16 vs 0.54 ± 0.19 mmol/L and increased similarly in both groups to 0.69 ± 0.38 vs 0.67 ± 0.36 on day 8 of treatment (P = .781 for change). A significantly higher decrease in total and direct bilirubin vs baseline was seen in the test group compared with the control group P < .05 between groups). In plasma and red blood cell phospholipids, eicosapentaenoic acid and docosahexaenoic acid were higher, and the n-6/n-3 fatty acid ratio was lower in the test group (P < .05 vs control). Conclusions: The lipid emulsion, based on a mixture of MCTs and soybean, olive, and fish oils, was safe and well tolerated by preterm infants while beneficially modulating the fatty acid profile. Copyright © 2012 American Society for Parenteral and Enteral Nutrition.

Ottoni C.,University of Rome Tor Vergata | Ottoni C.,University Ziekenhuizen | Ottoni C.,Catholic University of Leuven | Ottoni C.,University of Perugia | And 8 more authors.
PLoS ONE | Year: 2010

The Tuareg of the Fezzan region (Libya) are characterized by an extremely high frequency (61%) of haplogroup H1, a mitochondrial DNA (mtDNA) haplogroup that is common in all Western European populations. To define how and when H1 spread from Europe to North Africa up to the Central Sahara, in Fezzan, we investigated the complete mitochondrial genomes of eleven Libyan Tuareg belonging to H1. Coalescence time estimates suggest an arrival of the European H1 mtDNAs at about 8,000-9,000 years ago, while phylogenetic analyses reveal three novel H1 branches, termed H1v, H1w and H1x, which appear to be specific for North African populations, but whose frequencies can be extremely different even in relatively close Tuareg villages. Overall, these findings support the scenario of an arrival of haplogroup H1 in North Africa from Iberia at the beginning of the Holocene, as a consequence of the improvement in climate conditions after the Younger Dryas cold snap, followed by in situ formation of local H1 sub-haplogroups. This process of autochthonous differentiation continues in the Libyan Tuareg who, probably due to isolation and recent founder events, are characterized by village- specific maternal mtDNA lineages. © 2010 Ottoni et al.

Boyer D.S.,Retina Vitreous Associates | Goldbaum M.,University of Sao Paulo | Leys A.M.,University Ziekenhuizen | Starita C.,Pfizer
British Journal of Ophthalmology | Year: 2014

Objective: To assess the rate of pegaptanib-associated sustained intraocular pressure (IOP) elevation. Methods: A posthoc analysis was conducted on all IOP measurements, except the immediate 30-min postinjection, from all subjects randomised to pegaptanib 0.3 mg or sham injections continuously in the first 2 years of the Vascular endothelial growth factor Inhibition Study in Ocular Neovascularisation (V.I.S.I.O.N.) study. Measurements were taken with Goldmann applanation tonometer or Tonopen, except at baseline and in cases of an IOP reading >30 mm Hg when a Goldmann applanation tonometer was mandatory. Results: Of 221 subjects, IOP measurements ≥22 mm Hg were seen in 28/114 and 23/107 subjects of the pegaptanib and sham subgroups, respectively (p=0.6338) and measurements ≥24 mm Hg were observed in eight and eight subjects in the pegaptanib and sham groups, respectively. More than two measurements ≥22 mm Hg occurred in six and 10 subjects (p=0.3025), and more than two measurements ≥24 mm Hg were observed in one and four subjects in the pegaptanib and sham groups, respectively. One patient with sustained IOP elevation in the pegaptanib study group, and four in the sham group, had IOP lowering medication added during the course of the study. No subject required glaucoma surgery. Conclusions: In V.I.S.I.O.N., after 2 years, there was no evidence of sustained IOP elevation associated with pegaptanib 0.3 mg use.

Savige J.,Royal Melbourne Hospital | Savige J.,University of Melbourne | Sheth S.,Royal Childrens Hospital | Sheth S.,Bai Yamunabai Laxman Nair Charitable Hospital | And 5 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2015

Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Mutations in the COL4A5 (X-linked), or COL4A3 and COL4A4 (autosomal recessive) genes result in absence of the collagen IVα3α4α5 network from the basement membranes of the cornea, lens capsule, and retina and are associated with corneal opacities, anterior lenticonus, fleck retinopathy, and temporal retinal thinning. Typically, these features do not affect vision or, in the case of lenticonus, are correctable. In contrast, the rarer ophthalmic complications of posterior polymorphous corneal dystrophy, giant macular hole, andmaculopathy all produce visual loss. Many of the ocular features of Alport syndrome are common, easily recognizable, and thus, helpful diagnostically, and in identifying the likelihood of early-onset renal failure. Lenticonus and central fleck retinopathy strongly suggest the diagnosis ofAlport syndrome and are associated with renal failure before the age of 30 years, in males with X-linked disease. Sometimes, ophthalmic features suggest the mode of inheritance. A peripheral retinopathy in the mother of a male with hematuria suggests X-linked inheritance, and central retinopathy or lenticonus in a female means that recessive disease is likely. Ocular examination, retinal photography, and optical coherence tomography are widely available, safe, fast, inexpensive, and acceptable to patients. Ocular examination is particularly helpful in the diagnosis of Alport syndrome when genetic testing is not readily available or the results are inconclusive. It also detects complications, such as macular hole, for which new treatments are emerging. © 2015 by the American Society of Nephrology.

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