25 research outputs found

    The role of the aryl hydrocarbon receptor in normal and malignant B cell development

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    Development of a program for toric intraocular lens calculation considering posterior corneal astigmatism, incision-induced posterior corneal astigmatism, and effective lens position

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    Background: To evaluate the toric intraocular lens (IOL) calculation considering posterior corneal astigmatism, incision-induced posterior corneal astigmatism, and effective lens position (ELP). Methods Two thousand samples of corneal parameters with keratometric astigmatism >= 1.0 D were obtained using boot-strap methods. The probability distributions for incision-induced keratometric and posterior corneal astigmatisms, as well as ELP were estimated from the literature review. The predicted residual astigmatism error using method D with an IOL add power calculator (IAPC) was compared with those derived using methods A, B, and C through Monte-Carlo simulation. Method A considered the keratometric astigmatism and incision-induced keratometric astigmatism, method B considered posterior corneal astigmatism in addition to the A method, method C considered incision-induced posterior corneal astigmatism in addition to the B method, and method D considered ELP in addition to the C method. To verify the IAPC used in this study, the predicted toric IOL cylinder power and its axis using the IAPC were compared with ray-tracing simulation results. Results The median magnitude of the predicted residual astigmatism error using method D (0.25 diopters [D]) was smaller than that derived using methods A (0.42 D), B (0.38 D), and C (0.28 D) respectively. Linear regression analysis indicated that the predicted toric IOL cylinder power and its axis had excellent goodness-of-fit between the IAPC and ray-tracing simulation. Conclusions The IAPC is a simple but accurate method for predicting the toric IOL cylinder power and its axis considering posterior corneal astigmatism, incision-induced posterior corneal astigmatism, and ELP.SRC program of the Center for Galaxy Evolution Research (CGER) [2010-0027910]; Korea Astronomy and Space Science Institute under the RD program [2014-9-710-03]; Busan Sungmo Eye Hospital Sodam Scholarship Committee, Busan, South KoreaFirst Online: 19 August 2016; 12 month embargo.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

    Disruption of human plasma cell differentiation by an environmental polycyclic aromatic hydrocarbon: a mechanistic immunotoxicological study

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    Background: The AhR is a ligand-activated transcription factor that mediates immunosuppression induced by environmental PAH and HAH. Recently, a critical role for the AhR in development of T cells involved in autoimmunity (Th17 and Treg) has been demonstrated, supporting the hypothesis that the AhR plays a key role in immune regulation both in the presence and absence of environmental ligands. Despite these results with T cells systems, little is known of the role that the AhR plays in B cell development. We have demonstrated that B cell activation with CD40 ligand, a stimulus that models adaptive immunity, induces AhR expression in primary human B cells, suggesting that activation may increase human B cell sensitivity to AhR ligands and that the AhR may play a role in B cell development. Methods To test these possibilities, we developed an in vitro system in which activated human B cells expressing high AhR levels are induced to differentiate into plasma cells. Consequently, the effects of benzo [a]pyrene, a prototypic environmental AhR ligand, on plasma cell differentiation could be investigated and this chemical could be exploited essentially as drug probe to implicate the role of the AhR in plasma cell development. Results A previously unattainable level of B cell differentiation into plasma cells (up to 45% conversion) was observed. Benzo [a]pyrene significantly suppressed that differentiation. γ-Irradiation after an initial proliferation phase induced by CD40 ligand and immediately prior to initiation of the differentiation phase blocked cell growth but did not affect cell viability or plasma cell differentiation. B [a]P suppressed differentiation whether or not cell growth was inhibited by γ-irradiation. Conclusions 1) Extensive proliferation is not required during the differentiation phase per se for CD40L-activated human B cells to undergo plasma cell differentiation, and 2) an environmental PAH blocks both proliferation and differentiation of AhR expressing B cells. The results uncover a new mechanism by which environmentally ubiquitous PAHs may negatively impact human B cell-mediated immunity.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofNon UBCReviewedFacult
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