Publications by authors named "Hyo J Yang"

4 Publications

  • Page 1 of 1

Comparison of Sugammadex Dose for Intraoperative Neuromonitoring in Thyroid Surgery: A Randomized Controlled Trial.

Laryngoscope 2021 Mar 15. Epub 2021 Mar 15.

Department of Anesthesiology and Pain Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objectives/hypothesis: To compare effect of 1 and 2 mg/kg of sugammadex on the incidence of intraoperative bucking and intraoperative neuromonitoring (IONM) quality in thyroid surgery.

Study Design: Randomized controlled trial.

Methods: Patients qualified for thyroid surgery with IONM were eligible for this double-blind, randomized, controlled trial. After tracheal intubation with 0.6 mg/kg rocuronium, 1 or 2 mg/kg of sugammadex was administered to patients in group I or II, respectively. The quality of the IONM for the external branch of the superior laryngeal nerve (EBSLN) was evaluated (strong/intermediate/weak). The initial amplitude of electromyography for the vagus nerve (V1) and the recurrent laryngeal nerve (R1) were recorded. Intraoperative bucking movements was recorded.

Results: A total of 102 patients (51 in each group) completed the study. Time from sugammadex administration to initial checking for the EBSLN was not different between group I and II (25.0 ± 7.9 vs. 25.5 ± 9.0 minutes, P = .788). There was no difference in the neuromonitoring quality for the EBSLN between group I and II (strong/intermediate/weak: 46/5/0 vs. 50/1/0, P = .205). The amplitudes of V1 (1,086.3 ± 673.3 μV vs. 1,161.8 ± 727.5 μV, P = .588) and R1 (1,328.2 ± 934.1 μV vs. 1,410.5 ± 919.6 μV, P = .655) were comparable between the groups. Patients who experienced bucking were significantly fewer in the group I than the group II (13.7% vs. 35.3%, P = .020).

Conclusion: A dose of 1 mg/kg sugammadex induced less bucking than 2 m/kg while providing comparable IONM quality during thyroid surgery.

Level Of Evidence: 2. Laryngoscope, 2021.
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March 2021

Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40.

Nature 2017 12 13;552(7685):368-373. Epub 2017 Dec 13.

Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.

The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 ångström cryo-electron microscopy structure of mTORC1 and the 3.4 ångström structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain-substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR-PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites. These findings help explain how mTORC1 selects its substrates, how its kinase activity is controlled, and how it is activated by cancer-associated mutations.
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December 2017

mTOR kinase structure, mechanism and regulation.

Nature 2013 May 1;497(7448):217-23. Epub 2013 May 1.

Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.

The mammalian target of rapamycin (mTOR), a phosphoinositide 3-kinase-related protein kinase, controls cell growth in response to nutrients and growth factors and is frequently deregulated in cancer. Here we report co-crystal structures of a complex of truncated mTOR and mammalian lethal with SEC13 protein 8 (mLST8) with an ATP transition state mimic and with ATP-site inhibitors. The structures reveal an intrinsically active kinase conformation, with catalytic residues and a catalytic mechanism remarkably similar to canonical protein kinases. The active site is highly recessed owing to the FKBP12-rapamycin-binding (FRB) domain and an inhibitory helix protruding from the catalytic cleft. mTOR-activating mutations map to the structural framework that holds these elements in place, indicating that the kinase is controlled by restricted access. In vitro biochemistry shows that the FRB domain acts as a gatekeeper, with its rapamycin-binding site interacting with substrates to grant them access to the restricted active site. Rapamycin-FKBP12 inhibits the kinase by directly blocking substrate recruitment and by further restricting active-site access. The structures also reveal active-site residues and conformational changes that underlie inhibitor potency and specificity.
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May 2013