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Dirk Ysebaert

Other affiliations: University of Liège
Bio: Dirk Ysebaert is an academic researcher from University of Antwerp. The author has contributed to research in topics: Transplantation & Kidney. The author has an hindex of 33, co-authored 123 publications receiving 3557 citations. Previous affiliations of Dirk Ysebaert include University of Liège.


Papers
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TL;DR: After severe warm I/R renal injury, a pronounced acute tubular necrosis occurs during the first 12-24 h in the absence of a marked cellular infiltrate, but with an important renal MPO activity, reflecting the activation of the adhering inflammatory cells (polymorphonuclear cells (PMNs) and mainly monocytes/macrophages).
Abstract: (P<0.05)), became prominent at day 5 (1034±161 cells/mm2 vs sham=18±18 cells/mm2 (P<0.05)), and Background. Leukocyte adhesion/infiltration in response to renal ischaemia/reperfusion (I/R) injury is almost disappeared after 10 days. CD4+ cells ( W3/25) gradually increased from day 5, reaching a maximum a well-known but poorly understood phenomenon. The identification, kinetics, and exact role of these at day 10. A few CD8+ cells (OX-8) were apparent from days 3 until 10, but no B-cells (OX-33) were inflammatory cells in I/R injury and regeneration are still matters of debate. observed. Conclusions. After severe warm I/R renal injury, a Methods. Uninephrectomized rats were submitted to 60 min renal ischaemia by clamping of renal vessels. pronounced acute tubular necrosis occurs during the first 12–24 h in the absence of a marked cellular Results. Severe acute renal failure was observed, with maximum functional impairment on day 2. By 12 h infiltrate, but with an important renal MPO activity, reflecting the activation of the adhering inflammatory after the ischaemic event, up to 80% of proximal tubular cells in the outer stripe of outer medulla cells (polymorphonuclear cells (PMNs) and mainly monocytes/macrophages). Only later at the time and (OSOM ) were already severely damaged. Proliferation (proliferating cell nuclear antigen (PCNA) staining) site (OSOM ) of regeneration a sequential accumulation of monocytes/macrophages and T cells becomes promstarted after 24 h, reaching maximum activity on day 3. Regeneration of tubular morphology started on the inent, in contrast with the low number of neutrophils found in the kidney during the 10-day post-ischaemic 3rd day, and after 10 days 50% of tubules had regenerated completely. Interstitial leukocytes (OX-1 immuno- period. The non-specificity of the so-called neutrophilspecific identification methods (MPO activity, naphhistochemical staining) were already prominent at day 1, thereafter gradually increasing with time. The thol AS-D chloroacetate esterase, or mAb HIS-48 staining), cross-reacting with monocytes/macrophages, so-called neutrophil-specific identification methods (myeloperoxidase (MPO), chloroacetate esterase, mAb explains the controversy in literature concerning the number of PMNs in post-ischaemic injury. HIS-48) proved to be non-specific, since they also stained for macrophages, as demonstrated by flow Keywords: damage; kidney; macrophages; myelocytometry and the combination of these stainings with peroxidase; neutrophils; rat; regeneration the macrophage-specific ED-1 staining. MPO activity was already significantly increased at 1 h post-I/R (439±34%, P<0.005), reaching its maximum activity after 12 h of I/R (1159±138%, P<0.0005), declining Introduction thereafter. On the other hand, neutrophil presence investigated by H&E staining revealed only a few Ischaemia/reperfusion (I/R) injury is a common clinneutrophils in glomeruli, medullary rays, and OSOM ical event, still associated with high mortality and at 24 h after the ischaemic event (4.7±4.2 cells/mm2 morbidity [1], and lacking a specific therapy. Postvs controls=2.3±2.0 cells/mm2 (n.s.)), and remained ischaemic acute tubular necrosis (ATN ) is observed unchanged over the next 10 days. In contrast, signific- most frequently in patients after major surgery (cardiac ant monocyte/macrophage adhesion/infiltration ( ED-1 and aortic operations), trauma, severe hypovolaemia, staining) occurred at the OSOM at 24 h post-ischaemia burns, and others [2]. In addition, delayed graft func(at 24 h, 120±46 cells/mm2 vs sham=18±4 cells/mm2 tion of renal allografts is mainly caused by postischaemic ATN, with significant long-term graft

369 citations

Journal ArticleDOI
TL;DR: Blocking the b130/CD28 costimulatory pathway by CTLA-4 Ig (recombinant fusion protein) ameliorated renal dysfunction and decreased mononuclear cell infiltration in I/R of the kidney and it seems worthwhile to study a combination therapy using anti-inflammatory/anti-adhesion molecules in the early phase of I-R.

185 citations

Journal ArticleDOI
TL;DR: 1-year metabolic control can be reproducibly achieved and standardized by cultured islet cell grafts with defined β cell number.
Abstract: Islet grafts can induce insulin independence in type 1 diabetic patients, but their function is variable with only 10% insulin indepence after 5 years We investigated whether cultured grafts with defined β cell number help standardize metabolic outcome Nonuremic C-peptide-negative patients received an intraportal graft with 05–50 × 106 β cells per kilogram of body weight (kgBW) under antithymocyte globulin and mycophenolate mofetil plus tacrolimus Metabolic outcome at posttransplant (PT) month 2 was used to decide on a second graft under maintenance mycophenolate mofetil/tacrolimus Graft function was defined by C-peptide >05 ng/ml and reduced insulin needs, metabolic control by reductions in HbA1c, glycemia coefficient of variation, and hypoglycemia At PT month 2, graft function was present in 16 of 17 recipients of >2 × 106 β cells per kgBW versus 0 of 5 with lower number The nine patients with C-peptide >1 ng/ml and glycemia coefficient of variation of 2 × 106 β cells per kgBW Of the 20 recipients of at least one graft with >2 × 106 β cells per kgBW, 17 maintained graft function and metabolic control up to PT month 12 At PT month 12, β cell function in insulin-independent patients ranged around 25% of age-matched control values Thus, 1-year metabolic control can be reproducibly achieved and standardized by cultured islet cell grafts with defined β cell number

166 citations

Journal ArticleDOI
TL;DR: It is demonstrated that OPN favors macrophage recruitment to the postischemic kidney, inhibits apoptosis, and stimulates the development of renal fibrosis after an acute ischemic insult.

151 citations

Journal ArticleDOI
TL;DR: It is demonstrated that reporter gene-modified BMSC derived from ROSA26- L-S-L-Luciferase transgenic mice are immune-tolerated upon implantation in the CNS of syngeneic immunocompetent mice, providing a research model for studying survival and localisation of autologous B MSC implants in the central nervous system by real-time BLI and/or histological analysis in the absence of immunosuppressive therapy.
Abstract: Cell transplantation is likely to become an important therapeutic tool for the treatment of various traumatic and ischemic injuries to the central nervous system (CNS). However, in many pre-clinical cell therapy studies, reporter gene-assisted imaging of cellular implants in the CNS and potential reporter gene and/or cell-based immunogenicity, still remain challenging research topics. In this study, we performed cell implantation experiments in the CNS of immunocompetent mice using autologous (syngeneic) luciferase-expressing bone marrow-derived stromal cells (BMSC-Luc) cultured from ROSA26-L-S-L-Luciferase transgenic mice, and BMSC-Luc genetically modified using a lentivirus encoding the enhanced green fluorescence protein (eGFP) and the puromycin resistance gene (Pac) (BMSC-Luc/eGFP/Pac). Both reporter gene-modified BMSC populations displayed high engraftment capacity in the CNS of immunocompetent mice, despite potential immunogenicity of introduced reporter proteins, as demonstrated by real-time bioluminescence imaging (BLI) and histological analysis at different time-points post-implantation. In contrast, both BMSC-Luc and BMSC-Luc/eGFP/Pac did not survive upon intramuscular cell implantation, as demonstrated by real-time BLI at different time-points post-implantation. In addition, ELISPOT analysis demonstrated the induction of IFN-γ-producing CD8+ T-cells upon intramuscular cell implantation, but not upon intracerebral cell implantation, indicating that BMSC-Luc and BMSC-Luc/eGFP/Pac are immune-tolerated in the CNS. However, in our experimental transplantation model, results also indicated that reporter gene-specific immune-reactive T-cell responses were not the main contributors to the immunological rejection of BMSC-Luc or BMSC-Luc/eGFP/Pac upon intramuscular cell implantation. We here demonstrate that reporter gene-modified BMSC derived from ROSA26-L-S-L-Luciferase transgenic mice are immune-tolerated upon implantation in the CNS of syngeneic immunocompetent mice, providing a research model for studying survival and localisation of autologous BMSC implants in the CNS by real-time BLI and/or histological analysis in the absence of immunosuppressive therapy.

138 citations


Cited by
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TL;DR: This research examines the interaction between demand and socioeconomic attributes through Mixed Logit models and the state of art in the field of automatic transport systems in the CityMobil project.
Abstract: 2 1 The innovative transport systems and the CityMobil project 10 1.1 The research questions 10 2 The state of art in the field of automatic transport systems 12 2.1 Case studies and demand studies for innovative transport systems 12 3 The design and implementation of surveys 14 3.1 Definition of experimental design 14 3.2 Questionnaire design and delivery 16 3.3 First analyses on the collected sample 18 4 Calibration of Logit Multionomial demand models 21 4.1 Methodology 21 4.2 Calibration of the “full” model. 22 4.3 Calibration of the “final” model 24 4.4 The demand analysis through the final Multinomial Logit model 25 5 The analysis of interaction between the demand and socioeconomic attributes 31 5.1 Methodology 31 5.2 Application of Mixed Logit models to the demand 31 5.3 Analysis of the interactions between demand and socioeconomic attributes through Mixed Logit models 32 5.4 Mixed Logit model and interaction between age and the demand for the CTS 38 5.5 Demand analysis with Mixed Logit model 39 6 Final analyses and conclusions 45 6.1 Comparison between the results of the analyses 45 6.2 Conclusions 48 6.3 Answers to the research questions and future developments 52

4,784 citations

01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

4,408 citations

Journal ArticleDOI
TL;DR: Evidence suggests that patients who have had acute kidney injury are at increased risk of subsequent chronic kidney disease, and new diagnostic techniques (eg, renal biomarkers) might help with early diagnosis.

1,840 citations

Journal ArticleDOI
TL;DR: Emerging research data led to the establishment of collaborative working groups addressing issues like isolated ‘v’ lesion and incorporation of omics‐technologies, paving the way for future combination of graft biopsy and molecular parameters within the Banff process.

1,700 citations

Journal ArticleDOI
TL;DR: Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Starlings R: University of Chicago, Chicago, Illinois,USA; Chan M: university of Alberta, Edmonton, Alberta, Canada ; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA.
Abstract: Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Anderson A: University of Chicago, Chicago, Illinois, USA; Chan M: University of Alberta, Edmonton, Alberta, Canada; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA; Fedson S: University of Chicago, Chicago, Illinois, USA; Fisher P: Ochsner Clinic, New Orleans, Louisiana, USA; Gonzales-Stawinski G: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Martinelli L: Ospedale Niguarda, Milano, Italy; McGiffin D: University of Alabama, Birmingham, Alabama, USA; Parisi F: Ospedale Pediatrico Bambino Gesu, Rome, Italy; Smith J: Freeman Hospital, Newcastle upon Tyne, UK Task Force 2 Taylor D: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Meiser B: University of Munich/Grosshaden, Munich, Germany; Baran D: Newark Beth Israel Medical Center, Newark, New Jersey, USA; Carboni M: Duke University Medical Center, Durham, North Carolina, USA; Dengler T: University of Hidelberg, Heidelberg, Germany; Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, USA; Frigerio M: Ospedale Niguarda, Milano, Italy; Kfoury A: Intermountain Medical Center, Murray, Utah, USA; Kim D: University of Alberta, Edmonton, Alberta, Canada; Kobashigawa J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Shullo M: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Stehlik J: University of Utah, Salt Lake City, Utah, USA; Teuteberg J: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Uber P: University of Maryland, Baltimore, Maryland, USA; Zuckermann A: University of Vienna, Vienna, Austria. Task Force 3 Hunt S: Stanford University, Palo Alto, California, USA; Burch M: Great Ormond Street Hospital, London, UK; Bhat G: Advocate Christ Medical Center, Oak Lawn, Illinois, USA; Canter C: St. Louis Children Hospital, St. Louis, Missouri, USA; Chinnock R: Loma Linda University Children's Hospital, Loma Linda, California, USA; Crespo-Leiro M: Hospital Universitario A Coruna, La Coruna, Spain; Delgado R: Texas Heart Institute, Houston, Texas, USA; Dobbels F: Katholieke Universiteit Leuven, Leuven, Belgium; Grady K: Northwestern University, Chicago, Illlinois, USA; Kao W: University of Wisconsin, Madison Wisconsin, USA; Lamour J: Montefiore Medical Center, New York, New York, USA; Parry G: Freeman Hospital, Newcastle upon Tyne, UK; Patel J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Pini D: Istituto Clinico Humanitas, Rozzano, Italy; Pinney S: Mount Sinai Medical Center, New York, New York, USA; Towbin J: Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Wolfel G: University of Colorado, Denver, Colorado, USA Independent Reviewers Delgado D: University of Toronto, Toronto, Ontario, Canada; Eisen H: Drexler University College of Medicine, Philadelphia, Pennsylvania, USA; Goldberg L: University of Pennsylvania, Philadelphia, Pennsylvania, USA; Hosenpud J: Mayo Clinic, Jacksonville, Florida, USA; Johnson M: University of Wisconsin, Madison, Wisconsin, USA; Keogh A: St Vincent Hospital, Sidney, New South Wales, Australia; Lewis C: Papworth Hospital Cambridge, UK; O'Connell J: St. Joseph Hospital, Atlanta, Georgia, USA; Rogers J: Duke University Medical Center, Durham, North Carolina, USA; Ross H: University of Toronto, Toronto, Ontario, Canada; Russell S: Johns Hopkins Hospital, Baltimore, Maryland, USA; Vanhaecke J: University Hospital Gasthuisberg, Leuven, Belgium.

1,346 citations