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The signal transduction of the cAMP/cAMP-dependent protein kinase [protein kinase A (PKA)] pathway through multiple receptors is critical for many processes in all cell types. In T cells, the engagement of both the TCR-CD3 complex and the CD28 co-stimulatory molecule also induces cAMP, and subsequently activates PKA. It is believed that elevation of cAMP(More)
Production of transgenic animals is an important technique for studying various biological processes. However, whether the integration of a particular transgene occurs randomly in the mouse genome has not been determined. Analysis by fluorescence in situ hybridization of the integration sites of the 142 EGFP (a mutant of green fluorescent protein)(More)
Accumulating evidence suggests that PD-1, an immuno-inhibitory receptor expressed on activated T cells, regulates peripheral T cell tolerance. In particular, PD-1 is involved in the induction and/or maintenance of T cells' intrinsic unresponsiveness to previously encountered Ags, although the mechanism is yet to be determined. We used a simple experimental(More)
Calcitonin gene-related peptide (CGRP) is thought to be a prominent neuropeptide in cardiovascular regulation and neuroimmune modulation. There are two isoforms of CGRP (alphaCGRP and betaCGRP), and the main CGRP receptors are probably composed of a calcitonin receptor-like receptor (CLR) and a receptor activity-modifying protein (RAMP)1. However, the(More)
There were no significant differences in the pharmacokinetics of micafungin and expression of hepatic multidrug resistance-associated protein 2 (ABCC2/Mrp2) between analbuminemic and Sprague-Dawley rats. Micafungin bound strongly to high-density lipoprotein (HDL) and moderately to gamma globulin. These results suggest that HDL and gamma globulin contribute(More)
Programmed cell death-1 (PD-1) is an inhibitory coreceptor for T lymphocytes that provides feedback inhibition of T cell activation. Although PD-1's expression on T cells is known to be activation dependent, the factors that determine the timing, intensity, and duration of PD-1 expression in immune reactions are not fully understood. To address this(More)
The negative co-stimulatory receptor, programmed cell death 1 (PD-1), is induced on activated T cells and delivers inhibitory signals upon engagement with its ligands PD-L1 and PD-L2, which are expressed on various somatic cells and certain cancers. Accumulating evidence suggests that interfering with the PD-1-PD-L1 interaction may result in the restoration(More)
The drug transporter, multidrug resistance-associated protein 2 (ABCC2/Mrp2), is known to play important roles in excretion of various drugs. In the present study, we investigated whether Mrp2 is involved in the transport of micafungin, a newly developed antifungal agent. When Sprague-Dawley rats received an intravenous injection of micafungin (1 mg/kg) in(More)
In this study, the involvement of sulfate conjugation and drug efflux transporter multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of a new quinolone antimicrobial agent, garenoxacin, was investigated in Sprague-Dawley (SD) rats and Eisai hyperbilirubinemic rats (EHBRs) lacking Mrp2. The disappearance of(More)
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