Publications

Modulation by balancing activating and inhibitory receptors constitutes an important mechanism for regulating lymphocyte and myeloid cell effector responses. Using a microarray screen during parasitic helminth infection, we identified CD200 receptor-like 3 as a transcript highly expressed in basophils. Novel splice variants were present that generated proteins that differed in surface expression. The second immunoglobulin-like domain, encoded by exon 4, was required for cell surface expression and recruitment of DAP12 to the cell surface. Splice variants also generated unique cytoplasmic domains, which contributed to efficient pairing with DAP12. Despite expression on basophils and mast cells, which are integral components of allergic immunity, the absence of DAP12 did not alter effector cell recruitment or the host response elicited by helminth infection with Nippostrongylus brasiliensis.

Nuclear foci containing the promyelocytic leukemia protein (PML bodies), which occur in most cells, play a role in tumor suppression. Here, we demonstrate that CHFR, a mitotic checkpoint protein frequently inactivated in human cancers, is a dynamic component of PML bodies. Intermolecular fluorescence resonance energy transfer analysis identified a distinct fraction of CHFR that interacts with PML in living cells. This interaction modulates the nuclear distribution and mobility of CHFR. A trans-dominant mutant of CHFR that inhibits checkpoint function also prevents colocalization and interaction with PML. Conversely, the distribution and mobility of CHFR are perturbed in PML(-/-) cells, accompanied by aberrations in mitotic entry and the response to spindle depolymerization. Thus, PML bodies control the distribution, dynamics and function of CHFR. Our findings implicate the interaction between these tumor suppressors in a checkpoint response to microtubule poisons, an important class of anticancer drugs.

Hyperpolarized gases belong to a new class of MR contrast agents that, when inhaled, provide high temporal and spatial resolution images of the lung airspaces. At this time, hyperpolarized gas MRI is only being performed at a limited number of institutions. However, the availability of hyperpolarized gas MRI could increase dramatically in coming years as regulatory hurdles within the U.S. are surmounted. The intent of this paper is to provide an introduction to hyperpolarized gas MRI for the thoracic radiologist. It includes a description of the basic principles of hyperpolarized gas MRI and a review of the results of preliminary clinical investigations with this method.