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G protein-coupled receptors represent the largest class of drug discovery targets. Drugs that activate G protein-coupled receptors are classified as either agonists or partial agonists. To study the mechanism whereby these different classes of activating ligands modulate receptor function, we directly monitored ligand-induced conformational changes in the G(More)
The transition of rhodopsin from the inactive to the active state is associated with proton uptake at Glu(134) (1), and recent mutagenesis studies suggest that protonation of the homologous amino acid in the alpha(1B) adrenergic receptor (Asp(142)) may be involved in its mechanism of activation (2). To further explore the role of protonation in G(More)
OBJECTIVES In the emergency department (ED), a significant amount of radiation exposure is due to computed tomography (CT) scans performed for the diagnosis of appendicitis. Children are at increased risk of developing cancer from low-dose radiation and it is therefore desirable to utilize CT only when appropriate. Ultrasonography (US) eliminates radiation(More)
The majority of extracellular physiologic signaling molecules act by stimulating GTP-binding protein (G-protein)-coupled receptors (GPCRs). To monitor directly the formation of the active state of a prototypical GPCR, we devised a method to site specifically attach fluorescein to an endogenous cysteine (Cys-265) at the cytoplasmic end of transmembrane 6(More)
Agonist binding to G protein-coupled receptors is believed to promote a conformational change that leads to the formation of the active receptor state. However, the character of this conformational change which provides the important link between agonist binding and G protein coupling is not known. Here we report evidence that agonist binding to the beta2(More)
BACKGROUND Pain due to bone metastases is a common cause of cancer-related morbidity, with few options available for patients refractory to medical therapies and who do not respond to radiation therapy. This study assessed the safety and efficacy of magnetic resonance-guided focused ultrasound surgery (MRgFUS), a noninvasive method of thermal tissue(More)
BACKGROUND Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1(More)
A rapid, reliable radiation-free method of pediatric body venography might complement US by evaluating veins in the abdomen and pelvis and by providing a global depiction of venous anatomy. We describe a MR venography technique utilizing gadofosveset, a blood pool contrast agent, in children. The technique allows high-spatial-resolution imaging of the veins(More)
BACKGROUND MR-guided high-intensity focused ultrasound is a noninvasive treatment modality that uses focused ultrasound waves to thermally ablate tumors within the human body while minimizing side effects to surrounding healthy tissues. This technology is FDA-approved for certain tumors and has potential to be a noninvasive treatment option for extremity(More)
Movements of transmembrane segments (TMs) 3 and 6 play a key role in activation of G protein-coupled receptors. However, the underlying molecular processes that govern these movements, and accordingly control receptor activation, remain unclear. To elucidate the importance of the conserved aspartic acid (Asp-130) in the Asp-Arg-Tyr motif of the beta2(More)