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Institution

Utrecht University

EducationUtrecht, Utrecht, Netherlands
About: Utrecht University is a education organization based out in Utrecht, Utrecht, Netherlands. It is known for research contribution in the topics: Population & Poison control. The organization has 58176 authors who have published 139351 publications receiving 6214282 citations. The organization is also known as: UU & Universiteit Utrecht.


Papers
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Journal ArticleDOI
TL;DR: There was no convincing relationship between postmenopausal status and cardiovascular disease, however, there was a modest effect of early menopause on cardiovascular disease.
Abstract: OBJECTIVE: Loss of ovarian function and subsequent deficiency of endogenous estrogens is suggested to enhance cardiovascular disease risk and related death after menopause. The aim was to obtain valid estimates of the cardiovascular disease risk associated with postmenopausal status and early menopause. DESIGN: A literature search of observational studies was performed using PubMed and EMBASE (1966 to May 1, 2004). Eighteen studies on postmenopausal status and age at menopause in relation to cardiovascular disease were selected. Six studies investigated menopausal status, nine studies investigated menopausal age, and three studied both. General variance-based methods were used to pool relative risk estimates and corresponding 95% confidence intervals. Stratification was performed for study design, type of menopause, outcome, and adjustment for age and smoking. RESULTS: The pooled relative risk estimate for postmenopausal versus premenopausal status and cardiovascular disease was 1.36 (95% CI, 1.15-1.60). In the stratified analysis, the pooled effect was 0.96 (95% CI, 0.77-1.21) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 2.62 (95% CI, 2.05-3.35). For early menopause and cardiovascular disease, with the menopausal age category containing 50 years as a reference, the pooled relative risk estimate was 1.25 (95% CI, 1.15-1.35). In the stratified analysis, the pooled effect was 1.38 (95% CI, 1.21-1.58) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 4.55 (95% CI, 2.56-8.01). CONCLUSIONS: Overall, there was no convincing relationship between postmenopausal status and cardiovascular disease. However, there was a modest effect of early menopause on cardiovascular disease. The effect was more pronounced for women with an artificial menopause than for women with a natural menopause.

635 citations

Journal ArticleDOI
TL;DR: Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity.
Abstract: Objectives. To assess the prevalence of microalbuminuria in the general population, especially in nondiabetic and nonhypertensive subjects, and its association with known cardiovascular risk factors and cardiovascular morbidity. Design. Cross-sectional cohort study. Setting. Inhabitants of the city of Groningen, the Netherlands. Subjects. All inhabitants, aged between 28 and 75 years, were send a postal questionnaire and a vial to collect an early morning urine sample (n = 85 421). Of these 40 856 subjects (47.8%) responded. Cardiovascular risk factors and morbidity were validated in a well defined nondiabetic and nonhypertensive group of 5241 subjects. Main outcome measures. Microalbuminuria, self-reported cardiovascular risk and cardiovascular morbidity in the total study cohort, and additionally more detailed measurements in a subset of the total population. Results. Microalbuminuria (20-200 mg L-1) was present in 7.2% of the subjects and independently associated with age, gender, hypertension, diabetes, smoking, previous myocardial infarction and stroke. Some of these associations were already observed at albuminuria levels of 10-20 mg L-1. After exclusion of the diabetic and hypertensive subjects, microalbuminuria was still prevalent in 6.6% of the subjects. Conclusions. Microalbuminuria appears to be common not only in the general population but also in a nondiabetic, nonhypertensive population and is independently associated with increased cardiovascular risk factors and cardio-vascular morbidity. Importantly, some of these associations are present at urinary albumin levels currently considered to be normal. These findings suggest that urinary albumin measurements may be useful in early risk profiling and prevention of cardiovascular disease in the population at large.

635 citations

Journal ArticleDOI
TL;DR: It is concluded that recognition of the novel epitope cooperates with slow off-rate in determining the activity of CD20 Ab in activation of complement and induction of tumor cell lysis.
Abstract: We have previously defined a panel of fully human CD20 mAb. Most of these were unexpectedly efficient in their ability to recruit C1q to the surface of CD20-positive cells and mediate tumor lysis via activation of the classical pathway of complement. This complement-dependent cytotoxicity (CDC) potency appeared to relate to the unusually slow off-rate of these human Abs. However, we now present epitope-mapping data, which indicates that all human mAb bind a novel region of CD20 that may influence CDC potency. Epitope mapping, using both mutagenesis studies and overlapping 15-mer peptides of the extracellular loops of CD20, defined the amino acids required for binding by an extensive panel of mouse and human mAb. Binding by rituximab and mouse CD20 mAb, had an absolute requirement for alanine and proline at positions 170 and 172, respectively, within the large extracellular loop of CD20. Surprisingly, however, all of the human CD20 mAb recognize a completely novel epitope located N-terminally of this motif, also including the small extracellular loop of CD20. Thus, although off-rate may influence biological activity of mAb, another critical factor for determining CDC potency by CD20 mAb appears to be the region of the target molecule they recognize. We conclude that recognition of the novel epitope cooperates with slow off-rate in determining the activity of CD20 Ab in activation of complement and induction of tumor cell lysis.

634 citations

Journal ArticleDOI
TL;DR: The results indicate a pivotal role for endoglin in the balance of ALK1 and ALK5 signalling to regulate endothelial cell proliferation and blocks TGF‐β‐induced growth arrest by indirectly reducing T GF‐β/ALK5 signalling.
Abstract: Endoglin is a transmembrane accessory receptor for transforming growth factor-β (TGF-β) that is predominantly expressed on proliferating endothelial cells in culture and on angiogenic blood vessels in vivo. Endoglin, as well as other TGF-β signalling components, is essential during angiogenesis. Mutations in endoglin and activin receptor-like kinase 1 (ALK1), an endothelial specific TGF-β type I receptor, have been linked to the vascular disorder, hereditary haemorrhagic telangiectasia. However, the function of endoglin in TGF-β/ALK signalling has remained unclear. Here we report that endoglin is required for efficient TGF-β/ALK1 signalling, which indirectly inhibits TGF-β/ALK5 signalling. Endothelial cells lacking endoglin do not grow because TGF-β/ALK1 signalling is reduced and TGF-β/ALK5 signalling is increased. Surviving cells adapt to this imbalance by downregulating ALK5 expression in order to proliferate. The ability of endoglin to promote ALK1 signalling also explains why ectopic endoglin expression in endothelial cells promotes proliferation and blocks TGF-β-induced growth arrest by indirectly reducing TGF-β/ALK5 signalling. Our results indicate a pivotal role for endoglin in the balance of ALK1 and ALK5 signalling to regulate endothelial cell proliferation.

634 citations

Journal ArticleDOI
TL;DR: This paper provides additional background information on the checkCIF procedure and additional details for a number of ALERTS along with options for how to act on them.
Abstract: Authors of a paper that includes a new crystal-structure determination are expected to not only report the structural results of inter­est and their inter­pretation, but are also expected to archive in computer-readable CIF format the experimental data on which the crystal-structure analysis is based. Additionally, an IUCr/checkCIF validation report will be required for the review of a submitted paper. Such a validation report, automatically created from the deposited CIF file, lists as ALERTS not only potential errors or unusual findings, but also suggestions for improvement along with inter­esting information on the structure at hand. Major ALERTS for issues are expected to have been acted on already before the submission for publication or discussed in the associated paper and/or commented on in the CIF file. In addition, referees, readers and users of the data should be able to make their own judgment and inter­pretation of the underlying experimental data or perform their own calculations with the archived data. All the above is consistent with the FAIR (findable, accessible, inter­operable, and reusable) initiative [Helliwell (2019). Struct. Dyn. 6, 05430]. Validation can also be helpful for less experienced authors in pointing to and avoiding of crystal-structure determination and inter­pretation pitfalls. The IUCr web-based checkCIF server provides such a validation report, based on data uploaded in CIF format. Alternatively, a locally installable checkCIF version is available to be used iteratively during the structure-determination process. ALERTS come mostly as short single-line messages. There is also a short explanation of the ALERTS available through the IUCr web server or with the locally installed PLATON/checkCIF version. This paper provides additional background information on the checkCIF procedure and additional details for a number of ALERTS along with options for how to act on them.

634 citations


Authors

Showing all 58756 results

NameH-indexPapersCitations
Ronald C. Kessler2741332328983
Albert Hofman2672530321405
Douglas G. Altman2531001680344
Hans Clevers199793169673
Craig B. Thompson195557173172
Patrick W. Serruys1862427173210
Ruedi Aebersold182879141881
Dennis S. Charney179802122408
Kenneth S. Kendler1771327142251
Jean Louis Vincent1611667163721
Vilmundur Gudnason159837123802
Monique M.B. Breteler15954693762
Lex M. Bouter158767103034
Elio Riboli1581136110499
Roy F. Baumeister157650132987
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023429
20221,014
20218,992
20208,578
20197,862
20187,020