The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Bong-yun Cha - One of the best experts on this subject based on the ideXlab platform.

  • Refractory Graves ’ Disease Successfully Cured by Adjunctive Cholestyramine and Subsequent Total
    2016
    Co-Authors: Endocrinol Metab, Yeoree Yang, Seawon Hwang, Minji Kim, Yejee Lim, Min-hee Kim, Sohee Lee, Dong-jun Lim, Moo-il Kang, Bong-yun Cha
    Abstract:

    The three major forms of treatment for Graves thyrotoxicosis are antithyroid drugs, radioactive iodine therapy and thyroidectomy. Surgery is the definitive treatment for Graves thyrotoxicosis that is generally recommended when other treatments have failed or are contraindicated. Generally, thyrotoxic patients should be euthyroid before surgery to minimize potential complications which usually requires preoperative management with Thionamides or inorganic iodine. But several cases of refractory Graves ’ disease have shown resistance to conventional treatment. Here we report a 40-year-old female patient with Graves ’ disease who com-plained of thyrotoxic symptoms for 7 months. Her thyroid function test and thyroid autoantibody profiles were consistent with Graves ’ disease. One kind of Thionamides and β-blocker were started to control her disease. However, she was resistant to nearly all conventional medical therapies, including β-blockers, inorganic iodine, and two Thionamides. She experienced hepatotoxicity from the Thionamides. What was worse is her past history of serious allergic reaction to corticosteroids, which are often used to help control symptoms. A 2-week regimen of high-dose cholestyramine improved her uncontrolled thyrotoxicosis and subsequent thyroidectomy was successfully performed. In conclusion, cholestyramine could be administered as an effective and safe adjunc-tive agent for preoperative preparation in patients with severe hyperthyroid Graves ’ disease that is resistant to conventional thera-pies

  • refractory graves disease successfully cured by adjunctive cholestyramine and subsequent total thyroidectomy
    Endocrinology and Metabolism, 2015
    Co-Authors: Yeoree Yang, Seawon Hwang, Minji Kim, Yejee Lim, Min-hee Kim, Sohee Lee, Dong-jun Lim, Moo-il Kang, Bong-yun Cha
    Abstract:

    The three major forms of treatment for Graves thyrotoxicosis are antithyroid drugs, radioactive iodine therapy and thyroidectomy. Surgery is the definitive treatment for Graves thyrotoxicosis that is generally recommended when other treatments have failed or are contraindicated. Generally, thyrotoxic patients should be euthyroid before surgery to minimize potential complications which usually requires preoperative management with Thionamides or inorganic iodine. But several cases of refractory Graves' disease have shown resistance to conventional treatment. Here we report a 40-year-old female patient with Graves' disease who complained of thyrotoxic symptoms for 7 months. Her thyroid function test and thyroid autoantibody profiles were consistent with Graves' disease. One kind of Thionamides and β-blocker were started to control her disease. However, she was resistant to nearly all conventional medical therapies, including β-blockers, inorganic iodine, and two Thionamides. She experienced hepatotoxicity from the Thionamides. What was worse is her past history of serious allergic reaction to corticosteroids, which are often used to help control symptoms. A 2-week regimen of high-dose cholestyramine improved her uncontrolled thyrotoxicosis and subsequent thyroidectomy was successfully performed. In conclusion, cholestyramine could be administered as an effective and safe adjunctive agent for preoperative preparation in patients with severe hyperthyroid Graves's disease that is resistant to conventional therapies.

James E Petersson - One of the best experts on this subject based on the ideXlab platform.

  • improved modeling of thioamide fret quenching by including conformational restriction and coulomb coupling
    Journal of Physical Chemistry B, 2020
    Co-Authors: Jimin Yoon, John J Ferrie, James E Petersson
    Abstract:

    Thioamide-containing amino acids have been shown to quench a wide range of fluorophores through distinct mechanisms. Here, we quantitatively analyze the mechanism through which the thioamide functional group quenches the fluorescence of p-cyanophenylalanine (Cnf), tyrosine (Tyr), and tryptophan (Trp). By comparing PyRosetta simulations to published experiments performed on polyproline ruler peptides, we corroborate previous findings that both Cnf and Tyr quenching occurs via Forster resonance energy transfer (FRET), while Trp quenching occurs through an alternate mechanism such as Dexter transfer. Additionally, optimization of the peptide sampling scheme and comparison of thioamides attached to the peptide backbone and side chain revealed that the significant conformational restriction associated with the thioamide moiety results in a high sensitivity of the apparent FRET efficiency to underlying conformational differences. Moreover, by computing FRET efficiencies from structural models using a variety of approaches, we find that quantitative accuracy in the role of Coulomb coupling is required to explain contributions to the observed quenching efficiency from individual structures on a detailed level. Last, we demonstrate that these additional considerations improve our ability to predict thioamide quenching efficiencies observed during binding of thioamide-labeled peptides to fluorophore-labeled variants of calmodulin.

  • studies of thioamide effects on serine protease activity enable two site stabilization of cancer imaging peptides
    ACS Chemical Biology, 2020
    Co-Authors: Taylor M. Barrett, Chunxiao Liu, Xing S Chen, Sam Giannakoulias, Hoang Anh T Phan, Jieliang Wang, Keith E Keenan, Richard J Karpowicz, James E Petersson
    Abstract:

    Thioamide substitutions in peptides can be used as fluorescence quenchers in protease sensors and as stabilizing modifications of hormone analogs. To guide these applications in the context of serine proteases, we here examine the cleavage of several model substrates, scanning a thioamide between the P3 and P3' positions, and identify perturbing positions for thioamide substitution. While all serine proteases tested were affected by P1 thioamidation, certain proteases were also significantly affected by other thioamide positions. We demonstrate how these findings can be applied by harnessing the combined P3/P1 effect of a single thioamide on kallikrein proteolysis to protect two key positions in a neuropeptide Y-based imaging probe, increasing its serum half-life to >24 h while maintaining potency for binding to Y1 receptor expressing cells. Such stabilized peptide probes could find application in imaging cell populations in animal models or even in clinical applications such as fluorescence-guided surgery.

  • fluorescent probes for studying thioamide positional effects on proteolysis reveal insight into resistance to cysteine proteases
    ChemBioChem, 2019
    Co-Authors: Taylor M. Barrett, Chunxiao Liu, Xing Chen, John J Ferrie, James E Petersson
    Abstract:

    Thioamide substitutions of the peptide backbone have been shown to reduce proteolytic degradation, and this property can be used to generate competitive protease inhibitors and to stabilize peptides toward degradation in vivo. Here, we present a straightforward sensor design that allows a systematic study of the positional effects of thioamide substitution by using real-time fluorescence. Thioamide scanning in peptide substrates of five papain family cysteine proteases demonstrates that a thioamide at or near the scissile bond can slow proteolysis in all cases, but that the magnitude of the effects varies with position and protease in spite of high sequence homology. Mechanistic investigation of papain proteolysis reveals that the thioamide effects derive from reductions in both affinity (KM ) and turnover number (kcat ). Computational modeling allows these effects to be understood based on disruption of key enzyme-substrate hydrogen bonds, providing a model for future rational use of thioamides to confer cysteine protease resistance.

  • the effects of thioamide backbone substitution on protein stability a study in α helical β sheet and polyproline ii helical contexts
    Chemical Science, 2017
    Co-Authors: Christopher R Walters, Miklos D Szantaikis, Yitao Zhang, Zachary E Reinert, Seth W Horne, David M Chenoweth, James E Petersson
    Abstract:

    Thioamides are single atom substitutions of the peptide bond that serve as versatile probes of protein structure. Effective use of thioamides requires a robust understanding of the impact that the substitution has on a protein of interest. However, the thermodynamic effects of thioamide incorporation have only been studied in small structural motifs, and their influence on secondary structure in the context of full-length proteins is not known. Here we describe a comprehensive survey of thioamide substitutions in three benchmark protein systems (calmodulin, the B1 domain of protein G, and collagen) featuring the most prevalent secondary structure motifs: α-helix, β-sheet, and polyproline type II helix. We find that in most cases, effects on thermostability can be understood in terms of the positioning and local environment of the thioamide relative to proximal structural elements and hydrogen bonding networks. These observations set the stage for the rational design of thioamide substituted proteins with predictable stabilities.

  • labeling proteins with fluorophore thioamide forster resonant energy transfer pairs by combining unnatural amino acid mutagenesis and native chemical ligation
    Journal of the American Chemical Society, 2013
    Co-Authors: Rebecca F. Wissner, Solongo Batjargal, Colin M Fadzen, James E Petersson
    Abstract:

    We have recently shown that p-cyanophenylalanine (Cnf) and a thioamide can be used as a minimally perturbing Forster resonant energy transfer (FRET) pair to monitor protein conformation. We have also shown that thioamide analogues of natural amino acids can be incorporated into full-sized proteins through native chemical ligation. For intermolecular studies with Cnf/thioamide FRET pairs, Cnf can be incorporated into proteins expressed in Escherichia coli through unnatural amino acid mutagenesis using a Cnf-specific tRNA synthetase. For intramolecular studies, a Cnf-labeled protein fragment can be expressed in E. coli and then ligated to a thioamide-labeled peptide synthesized on solid phase. This combination of methods allows for rapid access to double-labeled proteins with a minimum of unnecessary chemical synthesis. We demonstrate the utility of this approach by studying the binding of peptides to the protein calmodulin and by determining the orientation of the N- and C-termini in the amyloidogenic prot...

Onyebuchi E. Okosieme - One of the best experts on this subject based on the ideXlab platform.

  • safety of antithyroid drugs in pregnancy update and therapy implications
    Expert Opinion on Drug Safety, 2020
    Co-Authors: Thanuya Francis, Onyebuchi E. Okosieme, Niroshan Francis, John Lazarus
    Abstract:

    Introduction: The Thionamide antithyroid drugs, methimazole (MMI), its pro-drug derivative carbimazole (CMZ), and propylthiouracil (PTU) are the mainstay of treatment for hyperthyroidism in pregnancy. However, antithyroid drugs carry risks of adverse effects that can affect fetal and maternal well-being.Areas covered: This review provides an update on the safety of antithyroid drugs in pregnancy, focusing on the most serious concerns of severe liver disease and congenital anomalies.Expert opinion: PTU-induced liver disease is uncommon but can run a catastrophic course in pregnancy with a risk of liver failure and threats to maternal or fetal survival. Acute pancreatitis is a relatively rare occurrence that has been linked to Thionamide use in a handful of reports in non-pregnant individuals. Observational studies on the risk of birth defects with antithyroid drug exposure in pregnancy overall show an increase in birth defect risk with exposure to CMZ/MMI, and to a lesser extent, PTU. Further studies are required to determine whether the currently recommended approach of switching between Thionamide drugs in pregnancy improves outcomes. Ultimately, a preventative strategy of offering definitive therapy to hyperthyroid women of childbearing potential offers the best approach to truly reduce the risks of antithyroid drug adverse effects in pregnancy.

  • Should radioiodine now be first line treatment for Graves’ disease?
    Thyroid Research, 2020
    Co-Authors: Onyebuchi E. Okosieme, Peter N. Taylor, Colin M. Dayan
    Abstract:

    Background Radioiodine represents a cost-effective treatment option for Graves’ disease. In the UK, it is traditionally reserved for patients who relapse after initial Thionamide therapy. In a change from current practice, the new guidelines of the National Institute for Health and Care Excellence (NICE) recommends that radioiodine should now be first line therapy for Graves’ disease. However, the safety of radioiodine with respect to long-term mortality risk has been the subject of recent debate. This analysis examines evidence from treatment related mortality studies in hyperthyroidism and discusses their implications for future Graves’ disease treatment strategies. Main body Some studies have suggested an excess mortality in radioiodine treated cohorts compared to the background population. In particular, a recent observational study reported a modest increase in cancer-related mortality in hyperthyroid patients exposed to radioiodine. The interpretation of these studies is however constrained by study designs that lacked Thionamide control groups or information on thyroid status and so could not distinguish the effect of treatment from disease. Two studies have shown survival advantages of radioiodine over Thionamide therapy, but these benefits were only seen when radioiodine was successful in controlling hyperthyroidism. Notably, increased mortality was associated with uncontrolled hyperthyroidism irrespective of therapy modality. Conclusions Early radioiodine treatment will potentially reduce mortality and should be offered to patients with severe disease. However, Thionamides are still suitable for patients with milder disease, contraindications to radioiodine, or individuals who choose to avoid permanent hypothyroidism. Ultimately, a patient individualised approach that prioritises early and sustained control of hyperthyroidism will improve long-term outcomes regardless of the therapy modality used.

Yeoree Yang - One of the best experts on this subject based on the ideXlab platform.

  • Refractory Graves ’ Disease Successfully Cured by Adjunctive Cholestyramine and Subsequent Total
    2016
    Co-Authors: Endocrinol Metab, Yeoree Yang, Seawon Hwang, Minji Kim, Yejee Lim, Min-hee Kim, Sohee Lee, Dong-jun Lim, Moo-il Kang, Bong-yun Cha
    Abstract:

    The three major forms of treatment for Graves thyrotoxicosis are antithyroid drugs, radioactive iodine therapy and thyroidectomy. Surgery is the definitive treatment for Graves thyrotoxicosis that is generally recommended when other treatments have failed or are contraindicated. Generally, thyrotoxic patients should be euthyroid before surgery to minimize potential complications which usually requires preoperative management with Thionamides or inorganic iodine. But several cases of refractory Graves ’ disease have shown resistance to conventional treatment. Here we report a 40-year-old female patient with Graves ’ disease who com-plained of thyrotoxic symptoms for 7 months. Her thyroid function test and thyroid autoantibody profiles were consistent with Graves ’ disease. One kind of Thionamides and β-blocker were started to control her disease. However, she was resistant to nearly all conventional medical therapies, including β-blockers, inorganic iodine, and two Thionamides. She experienced hepatotoxicity from the Thionamides. What was worse is her past history of serious allergic reaction to corticosteroids, which are often used to help control symptoms. A 2-week regimen of high-dose cholestyramine improved her uncontrolled thyrotoxicosis and subsequent thyroidectomy was successfully performed. In conclusion, cholestyramine could be administered as an effective and safe adjunc-tive agent for preoperative preparation in patients with severe hyperthyroid Graves ’ disease that is resistant to conventional thera-pies

  • refractory graves disease successfully cured by adjunctive cholestyramine and subsequent total thyroidectomy
    Endocrinology and Metabolism, 2015
    Co-Authors: Yeoree Yang, Seawon Hwang, Minji Kim, Yejee Lim, Min-hee Kim, Sohee Lee, Dong-jun Lim, Moo-il Kang, Bong-yun Cha
    Abstract:

    The three major forms of treatment for Graves thyrotoxicosis are antithyroid drugs, radioactive iodine therapy and thyroidectomy. Surgery is the definitive treatment for Graves thyrotoxicosis that is generally recommended when other treatments have failed or are contraindicated. Generally, thyrotoxic patients should be euthyroid before surgery to minimize potential complications which usually requires preoperative management with Thionamides or inorganic iodine. But several cases of refractory Graves' disease have shown resistance to conventional treatment. Here we report a 40-year-old female patient with Graves' disease who complained of thyrotoxic symptoms for 7 months. Her thyroid function test and thyroid autoantibody profiles were consistent with Graves' disease. One kind of Thionamides and β-blocker were started to control her disease. However, she was resistant to nearly all conventional medical therapies, including β-blockers, inorganic iodine, and two Thionamides. She experienced hepatotoxicity from the Thionamides. What was worse is her past history of serious allergic reaction to corticosteroids, which are often used to help control symptoms. A 2-week regimen of high-dose cholestyramine improved her uncontrolled thyrotoxicosis and subsequent thyroidectomy was successfully performed. In conclusion, cholestyramine could be administered as an effective and safe adjunctive agent for preoperative preparation in patients with severe hyperthyroid Graves's disease that is resistant to conventional therapies.

Takaki Kanbara - One of the best experts on this subject based on the ideXlab platform.