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Schaudien, D. (author), Harleman, J.H. (author), Bouallala, F. (author), Kuper, C.F. (author)Toxicologic pathology plays a crucial role in the identification and interpretation of substance-induced health effects. Histology of lymphoid organs is quite sensitive, although it does not flag every model immunotoxic substance. Subtle interferences of toxic compounds, like transmembrane signaling and cell activation, are often not detectable...bookPart 2018
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Ruehl-Fehlert, C. (author), Parker, G.A. (author), Elmore, S.A. (author), Kuper, C.F. (author)Cells of the immune system are found in every organ, from the classic lymphoid organs to tissues such as liver, mucosae, and omental adipose tissue. Toxicity to the immune system may be from a direct or indirect injury to lymphoid organs. The morphological responses range from lymphocyte depletion to proliferation, and may result in an increased...bookPart 2017
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Schaudien, D. (author), Harleman, H. (author), Bouallala, F. (author), Kuper, C.F. (author)Toxicologic pathology plays a crucial role in the identification and interpretation of substance-induced health effects. Histology of lymphoid organs is quite sensitive, although it does not flag every model immunotoxic substance. Subtle interferences of toxic compounds, like transmembrane signaling and cell activation, are often not detectable...bookPart 2014
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Hettne, K.M. (author), Boorsma, A. (author), van Dartel, D.A.M. (author), Goeman, J.J. (author), de Jong, E. (author), Piersma, A.H. (author), Stierum, R.H. (author), Kleinjans, J.C. (author), Kors, J.A. (author)Background: Availability of chemical response-specific lists of genes (gene sets) for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM), and that these can be used with gene set analysis (GSA) methods for chemical treatment...article 2013
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Menke, A. (author), Wolterbeek, A. (author), Snel, C. (author), Bruijntjes, J. (author), Groot, D.D. (author), Oostrum, L.V. (author), Waalkens, I. (author), Kuper, C.F. (author)Characteristic susceptibility to environmental and pharmaceutical exposure may occur during periods in life of marked histophysiological changes of the immune system. Perinatal development is such a period; pregnancy followed by lactation is potentially another one. Here, we explored the influence of pregnancy and lactation on the model...article 2012
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Tonk, E.C.M. (author), de Groot, D.M.G. (author), Penninks, A.H. (author), Waalkens - Berendsen, I.D.H. (author), Wolterbeek, A.P.M. (author), Slob, W. (author), Piersma, A.H. (author), van Loveren, H. (author), TNO Kwaliteit van Leven (author)Current developmental and reproductive toxicity protocols include only a limited set of parameters for effects on the developing immune system. In this study, a wide range of immunological parameters were included in a pre- and postnatal developmental toxicity study. Dose-response data were compared to determine the relative sensitivity of...article 2010
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Janssen, G.B. (author), Penninks, A.H. (author), Knippels, L.M.J. (author), van Zijverden, M. (author), Spanhaak, S. (author), TNO Kwaliteit van Leven (author)This paper describes studies performed with ERA-63 a low molecular weight pharmaceutical with intended immunomodulatory effects. Since this compound was also known to have estrogenic activity a non-conventional approach was taken in order to differentiate between estrogenic and non-estrogenic-induced immunomodulatory effects. EE was included not...article 2008
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Kuper, C.F. (author), Stierum, R.H. (author), Boorsma, A. (author), Schijf, M.A. (author), Prinsen, M. (author), Bruijntjes, J.P. (author), Bloksma, N. (author), Arts, J.H.E. (author), TNO Kwaliteit van Leven (author)All LMW respiratory allergens known to date can also induce skin allergy in test animals. The question here was if in turn skin allergens can induce allergy in the respiratory tract. Respiratory allergy was tested in Th2-prone Brown Norway (BN) rats by dermal sensitization with the contact allergen dinitrochlorobenzene (DNCB; 1%, day 0; 0.5%,...article 2008
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Frieke Kuper, C. (author), TNO Kwaliteit van Leven (author)Histologic examination of lymphoid organs has revealed immunotoxic effects of a broad range of substances. The thymus has proven especially sensitive. The relative lack of sensitivity of mucosa-associated lymphoid cells and tissues may be due to shortcomings in the way they are examined. Validation of ways to examine mucosal lymphoid tissues and...article 2006
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Mulder, S.J. (author), Mulder-Bos, G.C. (author), TNO Kwaliteit van Leven (author)Coeliac disease frequency increases by obscure reasons and affects in some Western countries as much as 1% of the populations. The second one of monozygotic twins does not develop the disease in 100% but only in 20-50%. To unravel these mysteries, literature was searched to determine the disease background and find suggestions for research and...article 2006
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Heijne, W.H.M. (author), Jonker, D. (author), Stierum, R.H. (author), van Ommen, B. (author), Groten, J.P. (author), TNO Kwaliteit van Leven (author)Benzene is an industrial chemical, component of automobile exhaust and cigarette smoke. After hepatic bioactivation benzene induces bone marrow, blood and hepatic toxicity. Using a toxicogenomics approach this study analysed the effects of benzene at three dose levels on gene expression in the liver after 28 daily doses. NMR based metabolomics...article 2005
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Germolec, D.R. (author), Kashon, M. (author), Nyska, A. (author), Kuper, C.F. (author), Portier, C. (author), Kommineni, C. (author), Johnson, K.A. (author), Luster, M.I. (author), TNO Voeding (author)The accuracy of extended histopathology to detect immunotoxic chemicals in female B6C3F1 mice was evaluated under the auspices of the National Toxicology Program (NTP). A workgroup was formed consisting of four pathologists who conducted extended histopathological evaluation of lymphoid tissues obtained from a subset of NTP toxicology studies,...article 2004
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Germolec, D.R. (author), Nyska, A. (author), Kashon, M. (author), Kuper, C.F. (author), Portier, C. (author), Kommineni, C. (author), Johnson, K.A. (author), Luster, M.I. (author), TNO Voeding (author)There has been considerable interest in the use of expanded histopathology as a primary screen for immunotoxicity assessment. To determine the utility of a semiquantitative histopathology approach for examining specific structural and architectural changes in lymphoid tissues, a validation effort was initiated. This study addresses the...article 2004
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Centraal Instituut voor Voedingsonderzoek TNO (author), Gennari, A. (author), Bol, M. (author), Seinen, W. (author), Penninks, A. (author), Pieters, R. (author)The organotin compounds di-n-butyltin dichloride (DBTC) and tri-n-butyltin chloride (TBTC) induce thymus atrophy in rats. At low doses they inhibit immature thymocyte proliferation, whereas at higher doses in particular TBTC induces apoptotic cell death. In vitro, a similar concentration-effect relationship was observed, i.e. low concentrations...article 2002
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Kuper, C.F. (author), Harleman, J.H. (author), Richter-Reichelm, H.B. (author), Vos, J.G. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Toxicologic pathology is crucial in the identification and characterization of health effects following exposure to xenobiotics, mainly in toxicity experiments in rodents. Regarding regulatory toxicology, histopathology of lymphoid organs and tissues is a cornerstone in the identification of immunotoxic compounds. A 2-tier testing system is...article 2000
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Noorman, F. (author), Braat, E.A.M. (author), Barrett-Bergshoeff, M.M. (author), Barbé, E. (author), van Leeuwen, A. (author), Lindeman, J. (author), Rijken, D.C. (author), TNO Preventie en Gezondheid (author)Recently we developed mouse monocloual antibodies (mAb) against the isolated human 175-kDa mannose receptor. In the present study we tested whether these mAb are suitable for the detection of the mannose receptor on cultured macrophages using flow cytometry and on cells in human tissues using immunohistochemistry. Human monocytes did not react...article 1997
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de Heer, C. (author), Schuurman, H.J. (author), Houben, G.F. (author), Pieters, R.H.H. (author), Penninks, A.H. (author), van Loveren, H. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)SCID mice engrafted with human fetal thymus and liver tissue fragments (SCID-hu mice) are currently considered as a new tool in human immunotoxicological risk assessment. Testing of various immunotoxicants exerting thymotoxicity via different intrathymic target cell types is necessary for validation of this model. Therefore, SCID-hu mice were...article 1995
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Pieters, R.H.H. (author), Punt, P. (author), Bol, M. (author), van Dijken, J.M. (author), Seinen, W. (author), Penninks, A.H. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)In the present study, we show that the thymus atrophy inducing compound DBTC stimulates the intracellular release, but not the influx, of Ca2+ elicited by cross-linking of the TcRαβ-CD3-complex on rat thymocytes and inhibits capping of TcRαβ. Similarities with the effects of cytochalasin B together with the finding that DBTC also inhibited...article 1995
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Nijhuis, E.W.P. (author), Nagelkerken, L. (author), Gaubius Instituut TNO (author)Aging is accompanied by a decline in immune reactivity which to a major extent can be attributed to changes at the level of the regulatory CD4+ T cells. In addition to evidence pointing to intrinsic defects, resulting in improper responsiveness of lymphocytes, it is likely that many age-related phenomena can be explained by a changed composition...article 1992
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Kruisbeek, A.M. (author), Instituut voor experimentele gerontologie TNO (author)In the present review the results obtained so far with thymic epithelial culture supernatants (TES) or cocultivation of potential precursor T cells with TE cells will be discussed and compared with the effects reported for other thymic factors in studies on T cell differentiation in vitro. These studies can be divided into those involved with T...article 1979
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