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Activity-based protein profiling reveals broad reactivity of the nerve agent sarin

TNO Defensie en Veiligheid (author), Tuin, A.W. (author), Mol, M.A.E. (author), van den Berg, R.M. (author), Fidder, A. (author), van der Marel, G.A. (author), Overkleeft, H.S. (author), Noort, D. (author)

Elucidation of noncholinesterase protein targets of organophosphates, and nerve agents in particular, may reveal additional mechanisms for their high toxicity as well as clues for novel therapeutic approaches toward intoxications with these agents. Within this framework, we here describe the synthesis of the activity-based probe 3, which...

article 2009

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Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys

Liu, J. (author), O'Brien, K.L. (author), Lynch, D.M. (author), Simmons, N.L. (author), La Porte, A. (author), Riggs, A.M. (author), Abbink, P. (author), Coffey, R.T. (author), Grandpre, L.E. (author), Seaman, M.S. (author), Landucci, G. (author), Forthal, D.N. (author), Montefiori, D.C. (author), Carville, A. (author), Mansfield, K.G. (author), Havenga, M.J. (author), Pau, M.G. (author), Goudsmit, J. (author), Barouch, D.H. (author), TNO Kwaliteit van Leven (author)

A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads after SIV challenge of rhesus...

article 2009

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Differentiation of primary adult microglia alters their response to TLR8-mediated activation but not their capacity as APC

Zuiderwijk-Sick, E.A. (author), van der Putten, C. (author), Bsibsi, M. (author), Deuzing, I.P. (author), de Boer, W. (author), Persoon-Deen, C. (author), Kondova, I. (author), Boven, L.A. (author), van Noort, J.M. (author), 't Hart, B.A. (author), Amor, S. (author), Bajramovic, J.J. (author), TNO Defensie en Veiligheid TNO Kwaliteit van Leven (author)

Activated microglia are found in a variety of neuroinflammatory disorders where they have attributed roles as effector as well as antigen-presenting cells (APC). Critical determinants for the multifaceted role of microglia are the differentiation potential of microglia and their mode of activation. In this study, we have investigated the effects...

article 2007

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Identification of soluble CD14 as an endogenous agonist for toll-like receptor 2 on human astrocytes by genome-scale functional screening of glial cell derived proteins

Bsibsi, M. (author), Bajramovic, J.J. (author), van Duijvenvoorden, E. (author), Persoon, C. (author), Ravid, R. (author), van Noort, J.M. (author), Vogt, M.H.J. (author), TNO Kwaliteit van Leven (author)

Human astrocytes express a limited repertoire of Toll-like receptor (TLR) family members including TLR1-4, which are expressed on the cell surface. Also, TLR3 but not TLR4 activation on astrocytes induces expression of several factors involved in neuroprotection and down-regulation of inflammation rather than in the onset of traditional pro...

article 2007

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Analysis of longitudinal metabolomics data

Jansen, J.J. (author), Hoefsloot, H.C.J. (author), Boelens, H.F.M. (author), van der Greef, J. (author), Smilde, A.K. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)

Motivation: Metabolomics datasets are generally large and complex. Using principal component analysis (PCA), a simplified view of the variation in the data is obtained. The PCA model can be interpreted and the processes underlying the variation in the data can be analysed. In metabolomics, often a priori information is present about the data....

article 2004

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Retrospective detection of exposure to nerve agents: Analysis of phosphofluoridates originating from fluoride-induced rectivation of phospylated BuChE

Prins Maurits Laboratorium TNO (author), van der Schans, M.J. (author), Polhuijs, M. (author), van Dijk, C. (author), Degenhardt, C.E.A.M. (author), Pleijsier, K. (author), Langenberg, J.P. (author), Benschop, H.P. (author)

The utility was explored of a new approach to detect retrospectively exposure to nerve agents by means of conversion of the inhibitor moiety bound to the active site of the enzyme BuChE in plasma with fluoride ions into a phosphofluoridate which is subsequently analyzed by means of gas chromatography (GC). This quantifies ≥0.01% inhibition of...

article 2004

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Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic-T-lymphocyte responses

O'Connor, D.H. (author), Mothe, B.R. (author), Weinfurter, J.T. (author), Fuenger, S. (author), Rehrauer, W.M. (author), Jing, P. (author), Rudersdorf, R.R. (author), Liebl, M.E. (author), Krebs, K. (author), Vasquez, J. (author), Dodds, E. (author), Loffredo, J. (author), Martin, S. (author), McDermott, A.B. (author), Allen, T.M. (author), Wang, C. (author), Doxiadis, G.G. (author), Montefiori, D.C. (author), Hughes, A. (author), Burton, D.R. (author), Allison, D.B. (author), Wolinsky, S.M. (author), Bontrop, R. (author), Picker, L.J. (author), Watkins, D.I. (author)

Certain major histocompatibility complex class I (MHC-I) alleles are associated with delayed disease progression in individuals infected with human immunodeficiency virus (HIV) and in macaques infected with simian immunodeficiency virus (SIV). However, little is known about the influence of these MHC alleles on acute-phase cellular immune...

article 2003

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Prophylactic and therapeutic effects of a humanized monoclonal antibody against the IL-2 receptor (DACLIZUMAB) on collagen-induced arthritis (CIA) in rhesus monkeys

Brok, H.P.M. (author), Tekoppele, J.M. (author), Hakimi, J. (author), Kerwin, J.A. (author), Nijenhuist, E.M. (author), de Groot, C.W. (author), Bontrop, R.E. (author), Hart 't, B.A. (author), Gaubius Instituut (author)

CIA in the rhesus monkey is an autoimmune-based polyarthritis with inflammation and erosion of synovial joints that shares various features with human rheumatoid arthritis (RA). The close phylogenetic relationship between man and rhesus monkey makes the model very suitable for preclinical safety and efficacy testing of new therapeutics with...

article 2001

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Dosimetry for total body irradiation of rhesus monkeys with 300 kV X- rays

Zoetelief, J. (author), Wagemaker, G. (author), Broerse, J.J. (author), Centrum voor Stralingsbescherming en Dosimetrie TNO (author)

Purpose: To obtain more accurate information on the dose distribution in rhesus monkeys for total body irradiation with orthovoltage X-rays. Materials and methods: Dose measurements were performed with an ionization chamber inside homogeneous cylindrical and rectangular phantoms of various dimensions and in phantoms containing lung-equivalent...

article 1998

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Collagen-induced arthritis in rhesus monkeys: Evaluation of markers for inflammation and joint degradation

't Hart, B.A. (author), Bank, R.A. (author), de Roos, J.A.D.M. (author), Brok, H. (author), Jonker, M. (author), Theuns, H.M. (author), Hakimi, J. (author), Koppele, J.M.Te. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

The objective of this study was to analyse parameters in rhesus monkey collagen-induced arthritis (CIA) with which the inflammation and destruction of the joints can be described in quantitative terms. CIA was induced in genetically susceptible and resistant monkeys, which can be distinguished on the basis of the dominant resistance marker Mamu...

article 1998

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Detection of total- and partial-body irradiation in a monkey model: A comparative study of chromosomal aberration, micronucleus and premature chromosome condensation assays

Centrum voor Stralingsbescherming en Dosimetrie TNO (author), Darroudi, F. (author), Natarajan, A.T. (author), Bentvelzen, P.A.J. (author), Heidt, P.J. (author), van Rotterdam, A. (author), Zoetelief, J. (author), Broerse, J.J. (author)

Purpose: To investigate the efficacy of three cytogenetic methods (dicentrics, micronuclei (MN) and premature chromosome condensation (PCC) analysis) for assessment of the unirradiated fraction and the persistence of damage after total-body (TB) and partial-body (PB) irradiation of rhesus monkeys (Macaca mulatta). Materials and methods: Animals...

article 1998

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Structural differences among serum IgA proteins of chimpanzee, rhesus monkey and rat origin

Endo, T. (author), Radl, J. (author), Mestecky, J. (author), TNO Preventie en Gezondheid (author)

Asparagine-linked sugar chains were quantitatively released from chimpanzee, Rhesus monkey and rat IgA proteins as oligosaccharides by hydrazinolysis, converted to radioactive oligosaccharides by reduction with NaB3H4, and separated into neutral and two acidic fractions by paper electrophoresis. The acidic oligosaccharides were converted to...

article 1997

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Allelic diversity at the Mhc-DP locus in rhesus macaques (Macaca mulatta)

Primatencentrum TNO (author), Slierendregt, B.L. (author), Otting, N. (author), Kenter, M. (author), Bontrop, R.E. (author)

Allelic diversity at the major histocompatibility complex class II DP locus of rhesus macaques was studied by sequencing exon 2 of Mamu-DPA1 and -DPB1 genes. The Mamu-DPA1 gene is apparently invariant, whereas the Mamu-DPB1 locus displays polymorphism. Here we report the characterization of 1 Mamu-DPA1 and 13 Mamu-DPB1 alleles which were...

article 1995

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Major histocompatibility complex class I-associated vaccine protection from simian immunodeficiency virus-infected peripheral blood cells

Heeney, J.L. (author), van Els, C. (author), de Vries, P. (author), ten Haaft, P. (author), Otting, N. (author), Koornstra, W. (author), Boes, J. (author), Dubbes, R. (author), Niphuis, H. (author), Dings, M. (author), Cranage, M. (author), Norley, S. (author), Jonker, M. (author), Bontrop, R.E. (author), Osterhaus, A. (author)

To evaluate the effectiveness of vaccine protection from infected cells from another individual of the same species, vaccinated rhesus macaques (Macaca mulatta) were challenged with peripheral blood mononuclear cells from another animal diagnosed with acquired immune deficiency syndrome (AIDS). Half of the simian immunodeficiency virus (SIV)...

article 1994

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Neurohypophyseal astrocytoma (Pituicytoma) in a rhesus monkey (Macaca mulatta)

Instituut voor Verouderings- en Vaatziekten Onderzoek TNO (author), HogenEsch, H. (author), Broerse, J.J. (author), Zurcher, C. (author)

Chemicals/CAS: Glial Fibrillary Acidic Protein; S100 Proteins; Vimentin

article 1992

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Induction of type II collagen-specific antibody production in blood lymphocyte cultures of Rhesus monkeys (Macaca mulatta) with collagen-induced arthritis using the immobilized native antigen

't Hart, B.A. (author), Botman, C.A.D. (author), Bakker, N.P.M. (author)

Peripheral blood mononuclear cells (PBMC) from Rhesus monkeys previously immunized with bovine type II collagen to induce arthritis were cultured with the same antigen. Because the native protein is poorly soluble in culture medium a heating step is often used. The antigen in this form induced PBMC proliferation, but epitopes for the induction...

article 1991

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Species specificity of human interleukin-3 demonstrated by cloning and expression of the homologous rhesus monkey (Macaca mulatta) gene

Burger, H. (author), van Leen, R.W. (author), Dorssers, L.C.J. (author), Persoon, N.L.M. (author), Lemson, P.J. (author), Wagemaker, G. (author), Instituut voor Toegepaste Radiobiologie en Immunologie TNO (author)

To enable preclinical studies on homologous interleukin-3 (IL-3) in primate species, we isolated the gene encoding Rhesus monkey IL-3 (RhIL-3). The nucleotide sequence of the RhIL-3 gene displayed 92.9% homology with that of the human IL-3 (hIL-3) gene. The isolated RhIL-3 gene encodes a 143-amino acid (aa) precursor polypeptide, nine C-terminal...

article 1990

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Origin of the electroretinogram in the intact macaque eye. I. Principal component analysis

Instituut voor Zintuigfysiologie TNO (author), Heynen, H. (author), van Norren, D. (author)

Responses to 400 msec flashes of white light were recorded at various depth in the retina of the intact macaque eye. A statistical technique, principal component analysis (PCA), was used to isolate independent components from the LERG, using the changing contribution of a cell's response to the LERG with retinal depth. Two approaches were...

article 1985

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Absence of a correlation between humoral and cellular responses to vaccinia virus and products of the major histocompatibility complex in rhesus monkeys

Stitz, L. (author), Kreeftenberg, J.G. (author), Loggen, H.G. (author), Balner, H. (author), Primatencentrum TNO (author)

62 Rhesus monkeys were tested at different times after vaccinia virus infection for virus-specific induction of lymphocyte proliferation in vitro or antibody production in vivo. No association was found between identifiable RhLA-controlled antigens and the strength of the cellular proliferative and/or humoral response. Chemicals/CAS: Antibodies,...

article 1981

document

In vivo immune stimulation by interferon during viral infection

Schellekens, H. (author), Weimar, W. (author), de Reus, A. (author), Bolhuis, R.L.H. (author), Cantell, K. (author), Instituut voor Experimentele Gerontologie TNO (author)

Chemicals/CAS: Adjuvants, Immunologic; Antibodies, Viral; Interferons, 9008-11-1

article 1981