Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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    Soluble E-selectin and soluble ICAM-1 levels as markers of the activity of atopic dermatitis in children
    Wolkerstorfer, A. ; Savelkoul, H.F.J. ; Waard van der Spek, F.B. de; Neijens, H.J. ; Meurs, T. van; Oranje, A.P. - \ 2003
    Pediatric Allergy and Immunology 14 (2003). - ISSN 0905-6157 - p. 302 - 306.
    intercellular-adhesion molecule-1 - eosinophil cationic protein - disease-activity - clinical activity - cells - inflammation - dressings - receptor - eczema - skin
    The expression of adhesion molecules is up-regulated in the skin of atopic dermatitis (AD) patients, and the levels of the soluble adhesion molecules sE-selectin and sICAM-1 have been reported to reflect the endothelial activation in the skin of AD patients. The objective of the study was to investigate the relationship between symptom score and levels of sE-selectin, sICAM-1 and sVCAM-1 before and after 2 weeks of treatment. Eighteen children with an exacerbation of AD were admitted and treated with corticosteroid dilutions under occlusive wet dressings (wet-wrap treatment). Symptom score (objective SCORAD) and levels of sE-selectin, sICAM-1, and sVCAM-1 were assessed before and after 2 weeks of treatment. A significant correlation between the objective SCORAD before treatment and the level of sE-selectin (p <0.05), but not the level of sICAM-1 (p = 0.7) or sVCAM-1 (p = 0.5) was observed. The treatment resulted in a high degree of remission, which was reflected by a significant decrease in the level of sICAM-1 (p <0.01), whereas there was only a trend in the level of sE-selectin to decrease (p = 0.08). The level of sE-selectin after 2 weeks of treatment still correlated significantly with the objective SCORAD before treatment (p <0.005). Soluble E-selectin is a relative objective marker for the severity of AD. SCORAD is a treatment-sensitive symptom of AD, whereas E-selectin may be a more stable underlying systemic representation of AD.
    Increased serum IL-10/IL-12 ratio in wheezing infants
    Koopman, L.P. ; Savelkoul, H.F.J. ; Benten, I.J. van; Gerritsen, J. ; Brunekreef, B. ; Neijens, H.J. - \ 2003
    Pediatric Allergy and Immunology 14 (2003). - ISSN 0905-6157 - p. 112 - 119.
    soluble e-selectin - atopic-dermatitis - interleukin-2 receptor - adhesion molecules - allergic diseases - il-10 production - t-cells - asthma - children - ige
    To investigate the association between various serum markers and atopic symptoms in the first year of life, and to evaluate the prognostic value of these markers for the development of wheezing and skin rash in the second year of life. Data of 86 children on the development of wheezing and skin rash in the first 2 years of life were collected prospectively, making use of parental completed questionnaires, weekly symptom cards, structured interview and physical examination. Serum markers (IL-10, IL-12, IL-13, eotaxin, sE-selectin, sICAM-1, sIL-2R) and total and specific IgE were determined at age 1. Children who developed wheezing in the first year of life had lower serum levels of IL-12 than children without symptoms (median 40.3 pg/ml vs. 49.0 pg/ml, p = 0.01) and a higher serum IL-10/IL-12 ratio (0.41 vs. 0.31, p = 0.001) at age 1. The IL-10/IL-12 ratio increased with an increasing number of wheezing episodes. Levels of sE-selectin in children with wheezing and in children with itchy skin rash in the first year of life were higher than in symptom free children (6.1 ng/ml and 5.9 ng/ml vs. 4.9 ng/ml, p = 0.01 and p = 0.03, respectively). Children who developed wheezing in the second year of life already had increased sICAM-1 levels at age 1. Children who developed wheezing in the first year of life showed a serum cytokine response that is skewed towards a T-helper 2 profile, with lower IL-12 levels and an increased IL-10/IL-12 ratio. Children who developed wheezing in the second year of life had elevated sICAM-1 levels at age 1. Follow-up of the children is needed to evaluate the prognostic value of various serum markers for the development of allergic disease in later childhood.
    Nieuw droogproces voor suikerklontjes met microgolfenergie
    Torringa, E. ; Neijens, H. - \ 2002
    Voedingsmiddelentechnologie 35 (2002). - ISSN 0042-7934 - p. 10 - 14.
    Immuunregulatie bij de ontwikkeling van allergie op de jonge kinderleeftijd.
    Stolte, H.H. ; Neijens, H.J. ; Savelkoul, H.F.J. - \ 2002
    Nederlands Tijdschrift voor Allergie 1 (2002). - ISSN 1568-2498 - p. 18 - 30.
    Clinico-immunological heterogeneity in Comel-Netherton syndrome
    Gysel, D. van; Koning, H. ; Baert, M.R. ; Savelkoul, H.F.J. ; Neijens, H.J. ; Oranje, A.P. - \ 2001
    Dermatology 202 (2001). - ISSN 1018-8665 - p. 99 - 107..
    Background: Comèl-Netherton syndrome (CN) is characterized by atopic-eczema-like skin abnormalities combined with linear ichthyotic lesions, hair shaft abnormalities and atopy with high IgE levels. Objective: Five children with CN are described. In 2 of the 3 CN patients still alive, analysis of cytokines regulating IgE synthesis was performed. Methods: In peripheral blood mononuclear cells and cultures of purified T cells, mRNA expression and protein production of interleukin 4 (IL-4), IL-13, IL-5 and interferon were analysed. The results were compared with the values in age-matched atopic dermatitis patients and healthy children. Results: The 5 CN patients showed striking differences in disease severity and evolution. Marked differences were found in several cytokines in the 2 analysed CN patients. Low percentages of natural killer cells were observed in both CN patients. Conclusion: The regulation of IgE production in patients with CN is varied and complex. The CN patients were heterogeneous in terms of Th2 skewing.
    Selective development of a strong Th2 cytokine profile in high-risk children who develop atopy: risk factors and regulatory role of IFN-? IL-4 and IL-10
    Velden, V.H.J. van der; Laan, M.P. ; Baert, M.R.M. ; Waal-Malefyt, R. de; Neijens, H.J. ; Savelkoul, H.F.J. - \ 2001
    Clinical and Experimental Allergy 31 (2001). - ISSN 0954-7894 - p. 997 - 1006..
    Background The immunological processes in early life and their relation to allergic sensitization leading to a Th2 cytokine profile are still not well understood. Objective To analyse the environmental and genetic risk factors and immunological responses at birth in relation to the development of atopic disease at 12 months of age in a longitudinal study of high-risk children. Methods High-risk children were followed from birth till 12 months of age. Mononuclear cells obtained at birth and 6 and 12 months thereafter were analysed for their proliferative and cytokine responses after polyclonal and allergen-specific stimulation. Results At 12 months of age 25 percent children had developed an atopic disease. Two atopic parents, parental smoking and atopic dermatitis of at least one of the parents were significant risk factors. In cord blood of newborns who developed atopy, an increased percentage of CD4 CD45RO cells and an increased polyclonal-stimulated proliferation were observed. Furthermore, an impaired allergen-induced, but not polyclonal-stimulated IFN- production was found, suggesting a regulatory defect. At 6 and 12 months of age, a strong Th2 profile (characterized by increased levels of IL-4, IL-5, and IL-13) after both polyclonal and, to a lesser extent, allergen-specific stimulation was found in the children developing atopy. Allergen-induced IL-10 production at 12 months of age was only observed in the non-atopic children. Conclusion Our data indicate that the first 6 months of life represent a critical time window for the initiation of immunological changes resulting in the development of atopy. The selective development of a Th2 cytokine profile in high-risk children who develop atopy is due to increased production of Th2 cytokines, possibly caused by impaired allergen-induced IFN- production in the neonatal period. Furthermore, the decreased allergen-induced IL-10 levels observed in the atopic children at 12 months of age may result in a lack of down-regulation of the inflammatory process.
    Markers for early sensitisation and inflammation in relation to allergic manifestations of atopic disease up to 2 years of age in 133 high-risk children
    Laan, M.P. ; Baert, M.R.M. ; Bijl, A.M.H. ; Vredendaal, A.E.C.M. ; Waard-van der Spek, F.B. de; Oranje, A.P. ; Savelkoul, H.F.J. ; Neijens, H.J. - \ 2000
    Clinical and Experimental Allergy 30 (2000). - ISSN 0954-7894 - p. 944 - 953..
    Background The combination of genetic susceptibility and environmental factors induce allergic sensitization and subsequently local inflammation, resulting in atopic manifestations. Objective To examine whether immunological features reflecting sensitization (total and specific IgE levels, allergen-induced proliferative responses and skin tests) and markers of inflammation (plasma sE-selectin and blood eosinophils) are related to the clinical expression of atopy and whether they precede atopic disease in children up to 2 years of age. Methods The development of these markers during the first 2 years of life was studied prospectively in 133 newborns at high risk to develop atopic disease. Results The prevalence of atopic disease increased from 25 percent at 12 months to 32 percent at 24 months of age. The children with food allergy at 12 months, who all had atopic dermatitis (AD), turned out to have asthma-like disease in 40 percent and AD in 100 percent at the age of 24 months. Total IgE levels increased with time and from 12 months onward levels started to differ markedly between atopics and nonatopics. Food-specific IgE antibodies were significantly associated with AD (relative risk [RR] = 2.39), food (RR = 1.32) and upper-airway allergy (RR = 1.20), and house dust mite-specific IgE antibodies with upper-airway allergy (RR = 5.00). A positive skin test was significantly associated with AD (RR = 2.90) and food allergy (RR = 1.36). The inflammation markers investigated, were not related to the clinical expression or preceded atopic disease at 2 years of age in high-risk children. Conclusion Positive skin tests and specific IgE to food or inhalant allergens were related to the clinical expression of different atopic diseases. The combination of AD and food allergy at 12 months reflected the strongest risk factor in this high risk cohort for the development of asthma-like disease at 24 months of age.
    Immune responses during allergic sensitization and the development of atopy
    Savelkoul, H.F.J. ; Neijens, H.J. - \ 2000
    Allergy 55 (2000). - ISSN 0105-4538 - p. 989 - 997..
    Peanut-specific responses in young children with atopic dermatitis: symposium 10 years ALASTAT
    Savelkoul, H.F.J. ; Laan, M.P. ; Baert, M.R.M. ; Oranje, A.P. ; Neijens, H.J. - \ 1998
    In: DPC symposia and meetings in the Benelux 1998 - p. 139 - 140.
    CD4+ cells proliferate after peanut-extract-specific and CD8+ cells proliferate after polyclonal stimulation of PBMC of children with atopic dermatitis
    Laan, M.P. ; Tibbe, G.J.M. ; Oranje, A.P. ; Bosmans, E.P.E. ; Neijens, H.J. ; Savelkoul, H.F.J. - \ 1998
    Clinical and Experimental Allergy 28 (1998)1. - ISSN 0954-7894 - p. 35 - 44.
    Background Few studies describe in vitro food-allergen induced proliferative responses and cytokine production of PBMC of children with atopic dermatitis. This is especially true for peanut-allergen. Objectives To analyse the specificity of the T cell in proliferative responses, in children with atopic dermatitis with or without peanut allergy and healthy age-matched children. Methods Proliferative responses were measured by [3H]-thymidine incorporation and by expression of the intracellular Ki67-antigen using flow cytometry after antigen-specific stimulation of PBMC with peanut-extract (day 7) or polyclonal stimulation with Phorbol-12myristate-13acetate and Ca-ionophore (day 3). Cytokine mRNA (Interferon-gamma (IFN), IL-4) was detected by semiquantitative RT-PCR. Cytokine production (IL-4, IFN) was measured by ELISA. Results Peanut-extract induced proliferative responses of PBMC from children with atopic dermatitis and peanut allergy (AD PA ) were significantly higher as compared with the other groups studied. Ki67-antigen double staining revealed that 80100 percent of the proliferating cells were CD4 . These proliferative responses correlated significantly with the increase in IL-4 mRNA expression after peanut-extract specific stimulation. After polyclonal stimulation, however, CD8 cells preferentially proliferated. The degree of proliferation after polyclonal stimulation correlated inversely with the ratio of IL-4/IFN production. Conclusions The principal responding population of T cells in proliferative responses is different after peanut-extract specific and polyclonal stimulation of PBMC from AD PA patients. Furthermore, we found indirect evidence that the PBMC fraction of AD PA children contains increased frequencies of peanut-specific T helper-2 cells.
    Soluble E-selectin, other markers of inflammation and disease severity in children with atopic dermatitis
    Wolkerstorfer, A. ; Laan, M.P. ; Savelkoul, H.F.J. ; Neijens, H.J. ; Mulder, P.G. ; Oudesluys-Murphy, A.M. ; Sukhai, R.N. ; Oranje, A.P. - \ 1998
    British journal of dermatology 138 (1998)3. - ISSN 0007-0963 - p. 431 - 435.
    E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are membrane-bound adhesion molecules which mediate the attachment of leucocytes to endothelial cells. These molecules are preferentially expressed on activated endothelium. The soluble forms of these molecules (sE-selectin, sP-selectin, sICAM-1 and sVCAM-1) are present in the circulation as a result of shedding. Some of the soluble adhesion molecules have been thought to reflect disease activity in atopic dermatitis (AD). To evaluate their potential to reflect disease activity in AD, we correlated their plasma concentration with clinical severity measured by objective SCORAD (SCORing Atopic Dermatitis). Furthermore, levels of total IgE, specific IgE, and eosinophil cationic protein (ECP) were determined. SCORAD and sE-selectin levels were significantly increased in children with specific IgE for both food and inhalation allergens (P < 0.05). ECP consistently showed an increase with the scores of SCORAD, but no statistical significance was reached. Disease activity was significantly correlated with the plasma levels of sE-selectin (rs = 0.6, P < 0.0005) but not with sP-selectin, sICAM-1 and sVCAM-1. This agrees with recent studies performed in adults with AD, and supports the potential of sE-selectin as a parameter for monitoring disease activity in young children with AD.
    Differences in the indoor environment during pregnancy between ducth and immigrant women living in Rotterdam.
    Koopman, L.P. ; Jongste, J.C. de; Praet, I. ; Kerkhof, M. ; Gerritsen, J. ; Strien, R. van; Brunekreef, B. ; Wijga, A. ; Smit, H.A. ; Neijens, H.J. - \ 1998
    European Respiratory Journal 12 (1998). - ISSN 0903-1936 - p. 441S - 441S.
    Response rates in the PIAMA-project: a study on the prevalence and incidence of asthma and mite allergy in the Netherlands.
    Strien, R. van; Brunekreef, B. ; Wijga, A. ; Smit, H.A. ; Koopman, L.P. ; Praet, I. ; Neijens, H.J. ; Jongste, J.C. de; Kerkhof, M. ; Gerritsen, J. - \ 1998
    European Respiratory Journal 12 (1998). - ISSN 0903-1936 - p. 210S - 210S.
    The role of early intervention in prevention of atopy: the PIAMA project.
    Gerritsen, J. ; Brunekreef, B. ; Kerkhof, M. ; Smit, J. ; Neijens, H. ; Jongste, J. de; Aalberse, R. - \ 1998
    In: 1st International Conference on Children's Health and Environment, Amsterdam The Netherlands (1998) E-WE-S3-3
    T cell subsets and cytokines in allergic and non-allergic children. I. Analysis of IL-4, IFN-? and IL-13 mRNA expression and protein production
    Koning, H. ; Neijens, H.J. ; Baert, M.R.M. ; Oranje, A.P. ; Savelkoul, H.F.J. - \ 1997
    Cytokine 9 (1997)6. - ISSN 1043-4666 - p. 416 - 426.
    Interleukin 4 (IL-4) and IL-13 are key cytokines inducing switching to immunoglobulin E (IgE), whereas interferon (IFN-) acts inhibitory on this process. We analysed whether differences existed in IL-4, IFN- and IL-13 mRNA expression and protein production between T cells of children with allergic and non-allergic asthma, atopic dermatitis and healthy control children. IL-4 mRNA expression was increased in stimulated T cells of children with allergic asthma and atopic dermatitis, but not in those with non-allergic asthma as compared with healthy controls. Thus the increase in IL-4 expression can be considered as an underlying mechanism of the allergic disease process and not so much of the asthmatic state of the children. In unstimulated T cells of children with atopic dermatitis increased IFN- mRNA expression with a reduced IFN- protein production was found, indicating a post-translational defect in IFN-. Differences in Il-13 expression between the groups were not significant, but IL-13 was significantly correlated with the height of the radio-allergo-sorbent test (RAST) class and with the severity scoring of atopic dermatitis (SCORAD) index. This indicates the clinical relevance of IL-13 for the degree of allergen-specific sensitization and severity of atopic dermatitis. In conclusion, the imbalance in IL-4 and IFN- secretion in patients with atopic dermatitis may reflect general T cell activation in the presence of an intrinsic defect of IFN- secretion. Author Keywords: allergy; children; IL-4; IFN-; IL-13
    T cell subsets and cytokines in allergic and non-allergic children. II. Analysis of IL-5 and IL-10 mRNA expression and protein production
    Koning, H. ; Neijens, H.J. ; Baert, M.R.M. ; Oranje, A.P. ; Savelkoul, H.F.J. - \ 1997
    Cytokine 9 (1997)6. - ISSN 1043-4666 - p. 427 - 436.
    Interleukin 5 (IL-5) has an enhancing effect on IL-4 induced immunoglobulin E (IgE) synthesis. Furthermore, IL-5 plays an important role in the differentiation, recruitment, activation and survival of eosinophils, IL-10 has a downmodulating effect on interferon (IFN-) production and can exert strong anti-inflammatory activities. Therefore, we analysed whether differences were present in IL-5 and IL-10 mRNA expression and protein production between T cells of children with allergic and non-allergic asthma, atopic dermatitis and healthy control children. We demonstrated significant increases in IL-5 mRNA expression and protein production in different T cell fractions of children with allergic and non-allergic asthma and children with atopic dermatitis as compared to healthy controls. This indicates that IL-5 is not only involved in allergy, but also plays a role in the inflammatory process of non-allergic asthma. Interestingly, IL-10 mRNA expression by purified T cells of children with allergic and non-allergic asthma and children with atopic dermatitis was strongly decreased as compared with that of healthy controls. In the peripheral blood mononuclear cell (PBMC) fraction, IL-10 mRNA expression was comparable between the four groups. We hypothesize that this decreased T cell derived IL-10 expression results in a lack of immunosuppression of the inflammatory process in these diseases. However, a role of monocyte derived IL-10 cannot be ruled out. Author Keywords: allergy; children; IL-5; IL-10
    Intrathecal production of interleukin-12 and gamma-interferon in patients with bacterial meningitis
    Kornelisse, R.F. ; Hack, C.E. ; Savelkoul, H.F.J. ; Pouw-Kraan, T.C.T.M. van der; Hop, W.C.J. ; Mierlo, G. van; Suur, M.H. ; Neijens, H.J. ; Groot, R. de - \ 1997
    Infection and Immunity 65 (1997)3. - ISSN 0019-9567 - p. 877 - 881.
    To assess the role of interleukin-12 (IL-12) and gamma interferon (IFN-gamma) in children with bacterial meningitis, bioactive IL-12 (p70) and the inactive subunit p40 and IFN-gamma were measured in serum and cerebrospinal fluid (CSF) from 35 children with bacterial meningitis and 10 control subjects. The production of IFN-gamma is induced by IL-12 with tumor necrosis factor alpha (TNF-alpha) as a costimulator and inhibited by IL-10. CSF concentrations of IL-12 p40 as well as those of IFN-gamma were markedly elevated, whereas IL-12 p70 was hardly detectable. Detectable CSF levels of IFN-gamma correlated positively with IL-12 p40 (r = 0.40, P = 0.02) and TNF-alpha (r = 0.46, P = 0.04) but not with IL-6, IL-8, or IL-10. In contrast to CSF levels of TNF-alpha, IL-12, and IL-10, those of IFN-gamma were significantly higher in patients with pneumococcal meningitis than in children with meningitis caused by Haemophilus influenzae and Neisseria meningitidis, presumably because of a high CSF TNF-alpha/IL-10 ratio in the former. We suggest that IL-12- and TNF-alpha-induced IFN-gamma production may contribute to the natural immunity against microorganisms in the CSF compartment during the acute phase of bacterial meningitis. -------------------------------------------------------------------------------- Write to PMC | PMC Home | PubMed NCBI | U.S. National Library of Medicine NIH | Department of Health and Human Services Privacy Policy | Disclaimer | Freedom of Information Act
    ETAC: de eerste resultaten
    Wolkerstorfer, A. ; Neijens, H.J. ; Savelkoul, H.F.J. ; Oudesluys-Murphy, A.M. ; Sukhai, R.N. ; Oranje, A.P. - \ 1997
    Modern Medicine 7 (1997). - ISSN 0929-0141 - p. 28 - 29..
    De preventie en incidentie van astma en mijtallergie (PIAMA-onderzoek): een prospectieve studie.
    Brunekreef, B. ; Aalberse, R.C. ; Gerritsen, J. ; Jongste, J.C. de; Kerkhof, M. ; Neijens, H.J. ; Praet, I. ; Rijcken, H.C.J. ; Smit, H.A. ; Strien, R. van; Wijga, A. - \ 1997
    Pulmonair 4 (1997). - ISSN 1380-6505 - p. 7 - 7.
    PIAMA: framework of a study on the Prevention and Incidence of Asthma and Mite Allergy.
    Strien, R.T. van; Praet, J. ; Kerkhof, M. ; Wijga, A. ; Jongste, J. de; Neijens, H. ; Gerritsen, J. ; Rijcken, B. ; Smit, H.A. ; Brunekreef, B. - \ 1997
    Journal of Allergy and Clinical Immunology 99 (1997). - ISSN 0091-6749 - p. S87 - S87.
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