Institution
Erasmus University Medical Center
Healthcare•Rotterdam, Zuid-Holland, Netherlands•
About: Erasmus University Medical Center is a healthcare organization based out in Rotterdam, Zuid-Holland, Netherlands. It is known for research contribution in the topics: Population & Medicine. The organization has 8162 authors who have published 11395 publications receiving 517117 citations.
Topics: Population, Medicine, Cancer, Transplantation, Breast cancer
Papers published on a yearly basis
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TL;DR: A high yield of FLCN mutations in clinically defined BHD families is confirmed and a substantially increased lifetime risk of renal cancer of 16% is found for F LCN mutation carriers, and a pneumothorax risk of 29%.
Abstract: Background: Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant condition caused by germline FLCN mutations, and characterised by fibrofolliculomas, pneumothorax and renal cancer. The renal cancer risk, cancer phenotype and pneumothorax risk of BHD have not yet been fully clarified. The main focus of this study was to assess the risk of renal cancer, the histological subtypes of renal tumours and the pneumothorax risk in BHD. Methods: In this study we present the clinical data of 115 FLCN mutation carriers from 35 BHD families. Results: Among 14 FLCN mutation carriers who developed renal cancer 7 were <50 years at onset and/or had multifocal/bilateral tumours. Five symptomatic patients developed metastatic disease. Two early-stage cases were diagnosed by surveillance. The majority of tumours showed characteristics of both eosinophilic variants of clear cell and chromophobe carcinoma. The estimated penetrance for renal cancer and pneumothorax was 16% (95% minimal confidence interval: 6-26%) and 29% (95% minimal confidence interval: 9-49%) at 70 years of age, respectively. The most frequent diagnosis in families without identified FLCN mutations was familial multiple discoid fibromas. Conclusion: We confirmed a high yield of FLCN mutations in clinically defined BHD families, we found a substantially increased lifetime risk of renal cancer of 16% for FLCN mutation carriers. The tumours were metastatic in 5 out of 14 patients and tumour histology was not specific for BHD. We found a pneumothorax risk of 29%. We discuss the implications of our findings for diagnosis and management of BHD.
142 citations
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TL;DR: The peripheral blood T- cell compartment of morbidly obese subjects is characterized by increased homeostatic T-cell proliferation to which cytokines IL-7 and CCL5, among others, might contribute, suggesting a more anti-inflammatory set point.
Abstract: Obesity is associated with local T-cell abnormalities in adipose tissue. Systemic obesity-related abnormalities in the peripheral blood T-cell compartment are not well defined. In this study, we investigated the peripheral blood T-cell compartment of morbidly obese and lean subjects. We determined all major T-cell subpopulations via six-color flow cytometry, including CD8+ and CD4+ T cells, CD4+ T-helper (Th) subpopulations, and natural CD4+CD25+FoxP3+ T-regulatory (Treg) cells. Moreover, molecular analyses to assess thymic output, T-cell proliferation (T-cell receptor excision circle analysis), and T-cell receptor-β (TCRB) repertoire (GeneScan analysis) were performed. In addition, we determined plasma levels of proinflammatory cytokines and cytokines associated with Th subpopulations and T-cell proliferation. Morbidly obese subjects had a selective increase in peripheral blood CD4+ naive, memory, natural CD4+CD25+FoxP3+ Treg, and Th2 T cells, whereas CD8+ T cells were normal. CD4+ and CD8+ T-cell proliferation was increased, whereas the TCRB repertoire was not significantly altered. Plasma levels of cytokines CCL5 and IL-7 were elevated. CD4+ T-cell numbers correlated positively with fasting insulin levels. The peripheral blood T-cell compartment of morbidly obese subjects is characterized by increased homeostatic T-cell proliferation to which cytokines IL-7 and CCL5, among others, might contribute. This is associated with increased CD4+ T cells, with skewing toward a Treg- and Th2-dominated phenotype, suggesting a more anti-inflammatory set point.
142 citations
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TL;DR: E ectopic expression of miR-17, -20,93 and -106, all AAAGUGC seed-containing miRNAs, increases proliferation, colony outgrowth and replating capacity of myeloid progenitors and results in enhanced P-ERK levels.
142 citations
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Erasmus University Medical Center1, French Institute of Health and Medical Research2, Pierre-and-Marie-Curie University3, University of Southampton4, St Mary's Hospital5, University Hospital Southampton NHS Foundation Trust6, University of Porto7, University of Leicester8, Copenhagen University Hospital9, University of Copenhagen10, University of Aberdeen11, Utrecht University12, University of Bologna13, Boston Children's Hospital14, University of Bristol15, University of Paris-Sud16, Southampton General Hospital17, Charité18, University of Würzburg19, University of Bern20, Karolinska Institutet21, Maastricht University22, University of Crete23, Centre for Health Protection24
TL;DR: Younger gestational age, smaller size for gestational Age, and greater infant weight gain were across the full ranges associated with childhood lung function and explain the risk of childhood asthma to a substantial extent.
Abstract: BACKGROUND: Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE: We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS: We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS: Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS: Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.
142 citations
Elizabeth K. Speliotes1, Elizabeth K. Speliotes2, Cristen J. Willer3, Sonja I. Berndt +410 more•Institutions (86)
TL;DR: In this article, the authors examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs and up to 125,931 additional individuals.
Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
142 citations
Authors
Showing all 8309 results
Name | H-index | Papers | Citations |
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Albert Hofman | 267 | 2530 | 321405 |
André G. Uitterlinden | 199 | 1229 | 156747 |
Patrick W. Serruys | 186 | 2427 | 173210 |
Cornelia M. van Duijn | 183 | 1030 | 146009 |
Tien Yin Wong | 160 | 1880 | 131830 |
Monique M.B. Breteler | 159 | 546 | 93762 |
Marjo-Riitta Järvelin | 156 | 923 | 100939 |
Fernando Rivadeneira | 146 | 628 | 86582 |
Ewout W. Steyerberg | 139 | 1226 | 84896 |
J. Wouter Jukema | 124 | 785 | 61555 |
Bart W. Koes | 124 | 730 | 57630 |
Albert D. M. E. Osterhaus | 124 | 955 | 83678 |
Jan K. Buitelaar | 123 | 1004 | 61880 |
Frits R. Rosendaal | 122 | 763 | 69043 |
Johan P. Mackenbach | 120 | 783 | 56705 |