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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 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 Near-field heating is a potential problem in focused ultrasound treatments, as it can result in thermal injury to skin, subcutaneous fat, and other tissues. Our goals were to determine if T2-based temperature mapping could be used reliably to measure near-field heating in adipose tissue and whether it is practical to perform such mapping during(More)
High intensity focused ultrasound (HIFU) ablation of the brain has been increasingly used as a non-invasive treatment for essential tremor and neuropathic pain. However, artifacts arise in magnetic resonance (MR) images as a result of dielectric properties of the water bath coupler and of the tissues being investigated. As radio frequency (RF) waves enter a(More)
Magnetic Resonance guided Focused Ultrasound (MRgFUS) is a non-invasive, non-ionizing treatment producing thermal ablation using high intensity focused ultra-sound and MR thermometry to denervate pain from bone metastases. A recent phase III study comparing MRgFUS to sham treatment for a painful bone metastasis allowed patients to be treated with concurrent(More)
Soft tissue tumors are a heterogeneous group of tumors arising from connective tissues. These tumors may be benign, benign but locally aggressive, or malignant. Surgery either alone or in combination with adjuvant therapies such as radiation or chemotherapy can potentially cure a patient with a soft tissue tumor. The morbidity and complications associated(More)
BACKGROUND Minocycline has proven anti-nociceptive effects, but the mechanism by which minocycline delays the development of allodynia and hyperalgesia after peripheral nerve injury remains unclear. Inflammatory cells, in particular macrophages, are critical components of the response to nerve injury. Using ultrasmall superparamagnetic iron oxide-magnetic(More)
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