Publications by authors named "Gwenda J Graham"

Context: The effects of GH replacement therapy in patients who develop GH deficiency (GHD) after cure of acromegaly have not been established in a placebo-controlled study.

Objective: The objective of the study was to determine whether GH replacement improves body composition, cardiovascular risk markers and quality of life in patients with GHD and prior acromegaly.

Design: This was a 6-month, randomized, placebo-controlled study.

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Objectives: We have developed an image-guided surgical system based on invisible near-infrared fluorescent light. Presently, the only clinically available near-infrared fluorophore is indocyanine green, which fluoresces at approximately 800 nm and is used for coronary angiography. Our objective was to determine whether methylene blue, already US Food and Drug Administration approved for other indications, has useful near-infrared fluorescence properties for image-guided cardiac surgery.

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Individuals whose platelets lack dense or alpha-granules suffer various degrees of abnormal bleeding, implying that granule cargo contributes to hemostasis. Despite these clinical observations, little is known regarding the effects of impaired platelet granule secretion on thrombus formation in vivo. In platelets, SNARE proteins mediate the membrane fusion events required for granule cargo release.

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Background: Imaging of thrombus formation in vivo has been limited by the inability to directly visualize and measure thrombi in large blood vessels in real time. Near-infrared light, with its superior tissue penetration and reduced scatter, could potentially solve this problem.

Methods And Results: Platelets were labeled with the near-infrared fluorophore IR-786.

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Evidence has been mounting for peripheral functions for tachykinins, a family of neuropeptides including substance P (SP), neurokinin A, and neurokinin B, which are recognized for their roles in the central and peripheral nervous system. The recent discovery of 4 new members of this family, the endokinins (EKA, B, C, and D), which are distributed peripherally, adds support to the notion that tachykinins have physiologic/endocrine roles in the periphery. In the present study we report a fundamental new function for tachykinins in the regulation of platelet function.

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In this study we show that both glycogen synthase kinase 3 (GSK3) isoforms, GSK3alpha and GSK3beta, are present in human platelets and are phosphorylated on Ser(21) and Ser(9), respectively, in platelets stimulated with collagen, convulxin and thrombin. Phosphorylation of GSK3alpha/beta was dependent on phosphoinositide 3-kinase (PI3K) activity and independent of platelet aggregation, and correlated with a decrease in GSK3 activity that was preserved by pre-incubating platelets with PI3K inhibitor LY294002. Three structurally distinct GSK3 inhibitors, lithium, SB415286 and TDZD-8, were found to inhibit platelet aggregation.

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