Esther de Vries

Bio: Esther de Vries is an academic researcher from Tilburg University. The author has contributed to research in topics: Common variable immunodeficiency & Medicine. The author has an hindex of 22, co-authored 80 publications receiving 1999 citations. Previous affiliations of Esther de Vries include St. Elizabeth Hospital & Bosch.

Haploinsufficiency of the NF-κB1 Subunit p50 in Common Variable Immunodeficiency

Abstract: Common variable immunodeficiency (CVID), characterized by recurrent infections, is the most prevalent symptomatic antibody deficiency. In ∼90% of CVID-affected individuals, no genetic cause of the disease has been identified. In a Dutch-Australian CVID-affected family, we identified a NFKB1 heterozygous splice-donor-site mutation (c.730+4A>G), causing in-frame skipping of exon 8. NFKB1 encodes the transcription-factor precursor p105, which is processed to p50 (canonical NF-κB pathway). The altered protein bearing an internal deletion (p.Asp191_Lys244delinsGlu; p105ΔEx8) is degraded, but is not processed to p50ΔEx8. Altered NF-κB1 proteins were also undetectable in a German CVID-affected family with a heterozygous in-frame exon 9 skipping mutation (c.835+2T>G) and in a CVID-affected family from New Zealand with a heterozygous frameshift mutation (c.465dupA) in exon 7. Given that residual p105 and p50—translated from the non-mutated alleles—were normal, and altered p50 proteins were absent, we conclude that the CVID phenotype in these families is caused by NF-κB1 p50 haploinsufficiency.

DNA methylation arrays as surrogate measures of cell mixture distribution

Abstract: Background: There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls. Results: Here we present a method, similar to regression calibration, for inferring changes in the distribution of white blood cells between different subpopulations (e.g. cases and controls) using DNA methylation signatures, in combination with a previously obtained external validation set consisting of signatures from purified leukocyte samples. We validate the fundamental idea in a cell mixture reconstruction experiment, then demonstrate our method on DNA methylation data sets from several studies, including data from a Head and Neck Squamous Cell Carcinoma (HNSCC) study and an ovarian cancer study. Our method produces results consistent with prior biological findings, thereby validating the approach. Conclusions: Our method, in combination with an appropriate external validation set, promises new opportunities for large-scale immunological studies of both disease states and noxious exposures.

わかりやすい障害者の権利条約 : 知的障害のある人の権利のために = Convention on the rights of persons with disabilities

Abstract: The present report is submitted in response to General Assembly resolution 61/106, by which the Assembly adopted the Convention on the Rights of Persons with Disabilities and the Optional Protocol thereto. As requested by the Assembly, a brief overview of the status of the Convention as at 3 August 2007 is presented. The report also contains a brief description of technical arrangements on staff and facilities made necessary for the effective performance of the functions of the Conference of States Parties and the Committee under the Convention and the Optional Protocol, and a description on the progressive implementation of standards and guidelines for the accessibility of facilities and services of the United Nations system. Recent efforts of the United Nations and agencies to disseminate information on the Convention and the Optional Protocol are also described.

Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy

Abstract: G Du Toit, G Roberts, PH Sayre N Engl J Med 2015;372:803–813 To evaluate strategies of early peanut consumption or avoidance for prevention of peanut allergy in patients at risk The participants were between 4 and 11 months of age at randomization They suffered from severe eczema, egg allergy, or both A total of 640 patients were evaluated over a 60-month period They were stratified according to their sensitivity to skin testing to peanut extract Those with no measureable wheal were evaluated as not sensitized, those with wheal diameters 1 to 4 mm were considered sensitized, and participants with >4-mm wheal were excluded Participants were randomized to receive an initial supervised feeding …

Quality of care.

Abstract: Editor – I am moved by Professor Allan's elegy to bygone NHS virtues of ‘calm caring and gentle pace of clinical life… and all the time in the world to deliver compassionate care' ( Clin Med October 2009 p 407). One's immediate instinct would be to say ‘Ah, but times have changed' – only