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283 results on '"Boekelheide K"'

1. Paving the way for application of next generation risk assessment to safety decision-making for cosmetic ingredients

Author

Dent, M.P., Vaillancourt, E., Thomas, R.S., Carmichael, P.L., Ouedraogo, G., Kojima, H., Barroso, J., Ansell, J., Barton-Maclaren, T.S., Bennekou, S.H., Boekelheide, K., Ezendam, J., Field, J., Fitzpatrick, S., Hatao, M., Kreiling, R., Lorencini, M., Mahony, C., Montemayor, B., Mazaro-Costa, R., Oliveira, J., Rogiers, V., Smegal, D., Taalman, R., Tokura, Y., Verma, R., Willett, C., and Yang, C.

Published
2021
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3. Predicting Later-Life Outcomes of Early-Life Exposures

Author

Boekelheide, K, Blumberg, B, Chapin, RE, Cote, I, Graziano, JH, Janesick, A, Lane, R, Lillycrop, K, Myatt, L, States, JC, Thayer, KA, Waalkes, MP, and Rogers, JM

Subjects
arsenic, development, epigenetics, exposure, fetal, malnutrition, obesogen, PPAR
Published
2012

6. Germ Cell Apoptosis

Author

Embree, M. E., Boekelheide, K., Stock, G., editor, Lessl, M., editor, Jégou, B., editor, Pineau, C., editor, and Saez, J., editor

Published
2000
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7. Paving the way for application of next generation risk assessment to safety decision-making for cosmetic ingredients

Author

Dent, M. P., Vaillancourt, E., Thomas, R. S., Carmichael, P L, Ouedraogo, G., Kojima, H, Barroso, J., Ansell, J., Barton-Maclaren, T. S., Bennekou, Susanne Hougaard, Boekelheide, K., Ezendam, J., Field, J., Fitzpatrick, S., Hatao, M., Kreiling, R., Lorencini, M., Mahony, C., Montemayor, B., Mazaro-Costa, R., Oliveira, J., Rogiers, V., Smegal, D., Taalman, R., Tokura, Y., Verma, R., Willett, C., Yang, C., Dent, M. P., Vaillancourt, E., Thomas, R. S., Carmichael, P L, Ouedraogo, G., Kojima, H, Barroso, J., Ansell, J., Barton-Maclaren, T. S., Bennekou, Susanne Hougaard, Boekelheide, K., Ezendam, J., Field, J., Fitzpatrick, S., Hatao, M., Kreiling, R., Lorencini, M., Mahony, C., Montemayor, B., Mazaro-Costa, R., Oliveira, J., Rogiers, V., Smegal, D., Taalman, R., Tokura, Y., Verma, R., Willett, C., and Yang, C.

Abstract

Next generation risk assessment (NGRA) is an exposure-led, hypothesis-driven approach that has the potential to support animal-free safety decision-making. However, significant effort is needed to develop and test the in vitro and in silico (computational) approaches that underpin NGRA to enable confident application in a regulatory context. A workshop was held in Montreal in 2019 to discuss where effort needs to be focussed and to agree on the steps needed to ensure safety decisions made on cosmetic ingredients are robust and protective. Workshop participants explored whether NGRA for cosmetic ingredients can be protective of human health, and reviewed examples of NGRA for cosmetic ingredients. From the limited examples available, it is clear that NGRA is still in its infancy, and further case studies are needed to determine whether safety decisions are sufficiently protective and not overly conservative. Seven areas were identified to help progress application of NGRA, including further investments in case studies that elaborate on scenarios frequently encountered by industry and regulators, including those where a 'high risk' conclusion would be expected. These will provide confidence that the tools and approaches can reliably discern differing levels of risk. Furthermore, frameworks to guide performance and reporting should be developed.

Published
2021

11. Overcoming barriers to non-animal risk assessments for anti-androgenic effects in humans

Author

Dent, M., Carmichael, P., Vantangoli, M., Boekelheide, K., Martin, Francis L, Dent, M., Carmichael, P., Vantangoli, M., Boekelheide, K., and Martin, Francis L

Abstract

Toxicology testing is undergoing a transformation from a system based on high-dose studies in animals to one founded primarily on in vitro methods that evaluate changes in normal cellular signalling pathways using human-relevant cells or tissues. This is a challenge for anti-androgenic effects in humans, since some parts of the hypothalamus-pituitary-testicular axis are not well represented by accepted in vitro methods. These include key events relating to gonadotropin releasing hormone (GnRH) signalling which could be affected at the level of the hypothalamus and pituitary. In vitro tools are needed to characterize either specific effects (such as GnRH receptor antagonism) or non-specific effects (such as general toxicity causing a reduction in gonadotropin release) before an integrated model of the HPT axis can be described. We have been evaluating how this could be achieved using human non-pituitary cells that express GnRH receptors and synthesize gonadotropins. Furthermore, tools to characterize a tipping point between endocrine activity and adversity need to be developed to allow an assessment that is more representative of the underlying biological response to endocrine active chemicals. To this end we have been developing and characterizing human derived scaffold-free prostate microtissues to provide morphological and molecular readouts to identify exposures that lead to adverse responses. Our ambition is to use these tools in an exposure-led safety assessment to enable robust safety decision making for endocrine active chemicals without use of animals ( Dent et al., 2015).

Published
2016

15. The use of biomarkers of toxicity for integrating in vitro hazard estimates into risk assessment for humans

Author

Blaauboer, B.J., Boekelheide, K., Clewell, H.J., Daneshian, M., Dingemans, M.M.L., Goldberg, A.M., Heneweer, M., Jaworska, J., Kramer, N.I., Leist, M., Seibert, H., Testai, E., Vandebriel, R.J., Yager, J.D., Zurlo, J., Risk Assessment of Toxic and Immunomodulatory Agents, and Dep IRAS

Abstract

The role that in vitro systems can play in toxicological risk assessment is determined by the appropriateness of the chosen methods, with respect to the way in which in vitro data can be extrapolated to the in vivo situation. This report presents the results of a workshop aimed at better defining the use of in vitro-derived biomarkers of toxicity (BoT) and determining the place these data can have in human risk assessment. As a result, a conceptual framework is presented for the incorporation of in vitro-derived toxicity data into the risk assessment process. The selection of BoT takes into account that they need to distinguish adverse and adaptive changes in cells. The framework defines the place of in vitro systems in the context of data on exposure, structural and physico-chemical properties, and toxicodynamic and biokinetic modeling. It outlines the determination of a proper point-of-departure (PoD) for in vitro-in vivo extrapolation, allowing implementation in risk assessment procedures. A BoT will need to take into account both the dynamics and the kinetics of the compound in the in vitro systems. For the implementation of the proposed framework it will be necessary to collect and collate data from existing literature and new in vitro test systems, as well as to categorize biomarkers of toxicity and their relation to pathways-of-toxicity. Moreover, data selection and integration need to be driven by their usefulness in a quantitative in vitro-in vivo extrapolation (QIVIVE).

Published
2012

19. The use of biomarkers of toxicity for integrating in vitro hazard estimates into risk assessment for humans

Author

Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Blaauboer, B.J., Boekelheide, K., Clewell, H.J., Daneshian, M., Dingemans, M.M.L., Goldberg, A.M., Heneweer, M., Jaworska, J., Kramer, N.I., Leist, M., Seibert, H., Testai, E., Vandebriel, R.J., Yager, J.D., Zurlo, J., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Blaauboer, B.J., Boekelheide, K., Clewell, H.J., Daneshian, M., Dingemans, M.M.L., Goldberg, A.M., Heneweer, M., Jaworska, J., Kramer, N.I., Leist, M., Seibert, H., Testai, E., Vandebriel, R.J., Yager, J.D., and Zurlo, J.

Published
2012

24. A tumorigenic murine Sertoli cell line that is temperature-sensitive for differentiation

Author

Boekelheide K, Sj, Hall, Jw, Lee, Nicholas Rhind, and Ks, Zaret

Subjects
Male, endocrine system, Sertoli Cells, urogenital system, Papillomavirus Infections, Temperature, Mice, Nude, Cell Differentiation, Simian virus 40, Cell Line, Injections, Mice, Tumor Virus Infections, Phenotype, Testis, Animals, Sertoli Cell Tumor, Neoplasm Invasiveness, Skin, Research Article
Abstract

The Sertoli cell is the epithelial cell within the seminiferous tubule responsible for supporting germ cells. Most current in vitro studies of Sertoli cell function use primary cultures because of the limited number of available Sertoli cell lines. In addition, few in vivo models of Sertoli cell malignancy have been described. In this study, a tumorigenic Sertoli cell line was developed by infection of isolated murine Sertoli cells by simian virus 40 tsA255; the ts mutation causes the inactivation of the large T antigen at elevated temperatures. A cloned Sertoli cell line, called S14-1, demonstrated temperature-dependent growth in soft agar and formed tumors in nude mice. Electron microscopy of the S14-1-derived tumor revealed extensive basal intercellular junctions and tubulobulbarlike processes supporting its Sertoli cell origin. Cytogenetic analysis showed that S14-1 cells were aneuploid with an average of 70 chromosomes per cell. At the nonpermissive (40 C) temperature, S14-1 cells in vitro demonstrated a reduced growth rate, enhanced secretion of transferrin, and increased expression of sulfated glycoprotein-2 messenger RNA, indicating the cells manifested increased differentiation following large T antigen inactivation. The murine S14-1 Sertoli cell line should be useful for both in vitro studies of Sertoli cell function and in vivo studies of Sertoli cell malignancy.

Published
1993

42. Sertoli cell processes have axoplasmic features: an ordered microtubule distribution and an abundant high molecular weight microtubule-associated protein (cytoplasmic dynein).

Author

Neely, M D and Boekelheide, K

Abstract

Microtubules in the cytoplasm of rat Sertoli cell stage VI-VIII testicular seminiferous epithelium were studied morphometrically by electron microscopy. The Sertoli cell microtubules demonstrated axonal features, being largely parallel in orientation and predominantly spaced one to two microtubule diameters apart, suggesting the presence of microtubule-bound spacer molecules. Testis microtubule-associated proteins (MAPs) were isolated by a taxol, salt elution procedure. Testis MAPs promoted microtubule assembly, but to a lesser degree than brain MAPs. High molecular weight MAPs, similar in electrophoretic mobilities to brain MAP-1 and MAP-2, were prominent components of total testis MAPs, though no shared immunoreactivity was detected between testis and brain high molecular weight MAPs using both polyclonal and monoclonal antibodies. Unlike brain high molecular weight MAPs, testis high molecular weight MAPs were not heat stable. Testis MAP composition, studied on postnatal days 5, 10, 15, and 24 and in the adult, changed dramatically during ontogeny. However, the expression of the major testis high molecular weight MAP, called HMW-2, was constitutive and independent of the development of mature germ cells. The Sertoli cell origin of HMW-2 was confirmed by identifying this protein as the major MAP found in an enriched Sertoli cell preparation and in two rat models of testicular injury characterized by germ cell depletion. HMW-2 was selectively released from testis microtubules by ATP and co-purified by sucrose density gradient centrifugation with MAP-1C, a neuronal cytoplasmic dynein. The inhibition of the microtubule-activated ATPase activity of HMW-2 by vanadate and erythro-(2-hydroxy-3-nonyl)adenine and its proteolytic breakdown by vanadate-dependent UV photocleavage confirmed the dynein-like nature of HMW-2. As demonstrated by this study, the neuronal and Sertoli cell cytoskeletons share morphological, structural and functional properties.

Published
1988
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44. THE NEUROFILAMENT NEUROPATHIES

Author

Anthony, D. C., primary, Boekelheide, K., additional, Giangaspero, F., additional, Allen, J. C., additional, Parks, H., additional, Priest, J. W., additional, Webster, D., additional, and Graham, D. G., additional

Published
1982
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