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- 저자 : Don O Kikkawa (검색결과 2 건)
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Phospholipase C-γ as a Potential Therapeutic Target for Graves’ Orbitopathy
노태훈,채민경,고재상,Don O Kikkawa,장선영,윤진숙 대한내분비학회 2023 Endocrinology and metabolism Vol.38 No.6
Background: Phospholipase C-γ (PLC-γ) plays a crucial role in immune responses and is related to the pathogenesis of various inflammatory disorders. In this study, we investigated the role of PLC-γ and the therapeutic effect of the PLC-specific inhibitor U73122 using orbital fibroblasts from patients with Graves’ orbitopathy (GO). Methods: The expression of phospholipase C gamma 1 (PLCG1) and phospholipase C gamma 2 (PLCG2) was evaluated using polymerase chain reaction in GO and normal orbital tissues/fibroblasts. The primary cultures of orbital fibroblasts were treated with non-toxic concentrations of U73122 with or without interleukin (IL)-1β to determine its therapeutic efficacy. The proinflammatory cytokine levels and activation of downstream signaling molecules were determined using Western blotting. Results: PLCG1 and PLCG2 mRNA expression was significantly higher in GO orbital tissues than in controls (P<0.05). PLCG1 and PLCG2 mRNA expression was significantly increased (P<0.05) in IL-1β, tumor necrosis factor-α, and a cluster of differentiation 40 ligand-stimulated GO fibroblasts. U73122 significantly inhibited the IL-1β-induced expression of proinflammatory molecules, including IL-6, IL-8, monocyte chemoattractant protein-1, cyclooxygenase-2, and intercellular adhesion molecule-1 (ICAM-1), and phosphorylated protein kinase B (p-Akt) and p38 (p-p38) kinase in GO fibroblasts, whereas it inhibited IL-6, IL-8, and ICAM-1, and p-Akt and c-Jun N-terminal kinase (p-JNK) in normal fibroblasts (P<0.05). Conclusion: PLC-γ-inhibiting U73122 suppressed the production of proinflammatory cytokines and the phosphorylation of Akt and p38 kinase in GO fibroblasts. This study indicates the implications of PLC-γ in GO pathogenesis and its potential as a therapeutic target for GO.
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김소열,최석규,양석우,DonOKikkawa,So Youl Kim,Suk Kyue Choi,Suk Woo Yang,Don O Kikkawa 대한안과학회 2006 대한안과학회지 Vol.47 No.10
Purpose: To evaluate the effect of strabismus surgery on proptosis in thyroid-related orbitopathy Methods: The medical records of 22 consecutive patients (38 eyes) undergoing strabismus surgery were reviewed. Data pertaining to number of muscles operated, the length of muscle recession, prior orbital decompression, and exophthalmometry (by either Hertel or Naugle devices) were evaluated. Results: Thirty-eight eyes in 22 patients with thyroid-related orbitopathy were studied before and after the muscle surgery. The mean change in exophthalmometry for all eyes was an increase of 0.6 mm (p<0.01). Eyes with prior decompression averaged a 0.9 mm increase following strabismus surgery (p<0.01); those without decompression averaged a 0.2 mm decrease, although not statistically significant. For eyes with multiple muscles operated on a given eye averaged 1.2 mm increase; in those with one muscle operated the average increase was 0.2 mm. In cases where the inferior rectus muscle was operated on, the average increase was 0.9 mm. When the total length of muscle recession was less than or equal to 5 mm, the mean exophthalmometric change was a increase of 0.3 mm. If more than 5 mm, the mean was an increase of 0.8 mm. Conclusions: Strabismus surgery on patients with thyroid-related orbitopathy can worsen proptosis, especially those with prior decompression. When planning for orbital decompression, the surgeon should consider this effect. Patients should be made aware of possible changes to their appearance.
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