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890 results on '"Engels, E A"'

14. Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection

Author

Zekavat, S. M. (Seyedeh M.), Lin, S.-H. (Shu-Hong), Bick, A. G. (Alexander G.), Liu, A. (Aoxing), Paruchuri, K. (Kaavya), Wang, C. (Chen), Uddin, M. M. (Md Mesbah), Ye, Y. (Yixuan), Yu, Z. (Zhaolong), Liu, X. (Xiaoxi), Kamatani, Y. (Yoichiro), Bhattacharya, R. (Romit), Pirruccello, J. P. (James P.), Pampana, A. (Akhil), Loh, P.-R. (Po-Ru), Kohli, P. (Puja), McCarroll, S. A. (Steven A.), Kiryluk, K. (Krzysztof), Neale, B. (Benjamin), Ionita-Laza, I. (Iuliana), Engels, E. A. (Eric A.), Brown, D. W. (Derek W.), Smoller, J. W. (Jordan W.), Green, R. (Robert), Karlson, E. W. (Elizabeth W.), Lebo, M. (Matthew), Ellinor, P. T. (Patrick T.), Weiss, S. T. (Scott T.), Daly, M. J. (Mark J.), T. B. (The Biobank Japan Project), F. C. (FinnGen Consortium), Terao, C. (Chikashi), Zhao, H. (Hongyu), Ebert, B. L. (Benjamin L.), Reilly, M. P. (Muredach P.), Ganna, A. (Andrea), Machiela, M. J. (Mitchell J.), Genovese, G. (Giulio), and Natarajan, P. (Pradeep)

Abstract

Age is the dominant risk factor for infectious diseases, but the mechanisms linking age to infectious disease risk are incompletely understood. Age–related mosaic chromosomal alterations (mCAs) detected from genotyping of blood–derived DNA, are structural somatic variants indicative of clonal hematopoiesis, and are associated with aberrant leukocyte cell counts, hematological malignancy, and mortality. Here, we show that mCAs predispose to diverse types of infections. We analyzed mCAs from 768,762 individuals without hematological cancer at the time of DNA acquisition across five biobanks. Expanded autosomal mCAs were associated with diverse incident infections (hazard ratio (HR) 1.25; 95% confidence interval (CI) = 1.15–1.36; P = 1.8 x 10-7), including sepsis (HR 2.68; 95% CI = 2.25–3.19; P = 3.1 x 10-28), pneumonia (HR 1.76; 95% CI = 1.53–2.03; P = 2.3 x 10-15), digestive system infections (HR 1.51; 95% CI = 1.32–1.73; P = 2.2 x 10-9) and genitourinary infections (HR 1.25; 95% CI = 1.11–1.41; P = 3.7 x 10-4). A genome–wide association study of expanded mCAs identified 63 loci, which were enriched at transcriptional regulatory sites for immune cells. These results suggest that mCAs are a marker of impaired immunity and confer increased predisposition to infections.

Published
2021

20. Electrocardiographic characteristics of patients with coronavirus disease 2019 (COVID-2019) related pneumonia at first presentation

Author

Nguyen, U, primary, Strik, M, additional, Abu-Arib, S, additional, Bruekers, A, additional, Nguyen, T, additional, Massud, A, additional, Willems, R, additional, Dekker, S, additional, Spaetgens, B, additional, Engels, E, additional, Crijns, HGJM, additional, Koopmans, R, additional, Henry, R, additional, and Stehouwer, CDA, additional

Published
2021
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33. Maturation of white adipose tissue function in C57BL/6j mice from weaning to young adulthood

Author

Kodde, A., Engels, E., Oosting, A., van Limpt, K., van der Beek, E., Keijer, J., Kodde, A., Engels, E., Oosting, A., van Limpt, K., van der Beek, E., and Keijer, J.

Abstract

White adipose tissue (WAT) distribution and WAT mitochondrial function contribute to total body metabolic health throughout life. Nutritional interventions starting in the postweaning period may impact later life WAT health and function. We therefore assessed changes in mitochondrial density and function markers in WAT depots of young mice. Inguinal (ING), epididymal (EPI) and retroperitoneal (RP) WAT of 21, 42 and 98 days old C57BL/6j mice was collected. Mitochondrial density [citrate synthase (CS), mtDNA] and function [subunits of oxidative phosphorylation complexes (OXPHOS)] markers were analyzed, together with gene expression of browning markers (Ucp1, Cidea). mRNA of ING WAT of 21 and 98 old mice was sequenced to further investigate functional changes of the mitochondria and alterations in cell populations. CS levels decreased significantly over time in all depots. ING showed most pronounced changes, including significantly decreased levels of OXPHOS complex I, II, and III subunits and gene expression of Ucp1 (PN21-42 and PN42-98) and Cidea (PN42-98). White adipocyte markers were higher at PN98 in ING WAT. Analyses of RNA sequence data showed that the mitochondrial functional profile changed over time from “growth-supporting” mitochondria focused on ATP production (and dissipation), to more steady-state mitochondria with more diverse functions and higher biosynthesis. Mitochondrial density and energy metabolism markers declined in all three depots over time after weaning. This was most pronounced in ING WAT and associated with reduced browning markers, increased whitening and an altered metabolism. In particular the PN21-42 period may provide a time window to study mitochondrial adaptation and effects of nutritional exposures relevant for later life metabolic health.

Published
2019

47. HPV-Related Cancers after Solid Organ Transplantation in the US

Author

Madeleine, M. M., Finch, J. L., Lynch, C. F., Goodman, M. T., and Engels, E. A.

Subjects
Adult, Immunosuppression Therapy, Male, Adolescent, Vulvar Neoplasms, Incidence, Papillomavirus Infections, Uterine Cervical Neoplasms, Organ Transplantation, Middle Aged, Anus Neoplasms, Article, Tacrolimus, United States, Cohort Studies, Oropharyngeal Neoplasms, Young Adult, Humans, Female, Registries, Penile Neoplasms
Abstract

Transplant recipients have elevated cancer risk including risk of human papillomavirus (HPV)-associated cancers of the cervix, anus, penis, vagina, vulva, and oropharynx. We examined the incidence of HPV-related cancers in 187,649 U.S. recipients in the Transplant Cancer Match Study. Standardized incidence ratios (SIRs) compared incidence rates to the general population, and incidence rate ratios (IRR) compared rates across transplant subgroups. We observed elevated incidence of HPV-related cancers (SIRs: in situ 3.3–20.3, invasive 2.2–7.3), except for invasive cervical cancer (SIR 1.0). Incidence increased with time since transplant for vulvar, anal, and penile cancers (IRRs 2.1–4.6 for 5+ vs.

Published
2013

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