We herein investigated the role of the STAT signaling cascade in the production of pro-inflammatory cytokines and cisplatin ototoxicity. A significant hearing impairment caused by cisplatin injection was observed in Balb/c (wild type, WT) and STAT4 −/− , but not in STAT6 −/− mice. Moreover, the expression levels of the protein and mRNA of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, were markedly increased in the serum and cochlea of WT and STAT4 −/− , but not STAT6 −/− mice. Organotypic culture revealed that the shape of stereocilia bundles and arrays of sensory hair cell layers in the organ of Corti from STAT6 −/− mice were intact after treatment with cisplatin, whereas those from WT and STAT4 −/− mice were highly distorted and disarrayed after the treatment. Cisplatin induced the phosphorylation of STAT6 in HEI-OC1 auditory cells, and the knockdown of STAT6 by STAT6-specific siRNA significantly protected HEI-OC1 auditory cells from cisplatin-induced cell death and inhibited pro-inflammatory cytokine production. We further demonstrated that IL-4 and IL-13 induced by cisplatin modulated the phosphorylation of STAT6 by binding with IL-4 receptor alpha and IL-13Rα1. These findings suggest that STAT6 signaling plays a pivotal role in cisplatin-mediated pro-inflammatory cytokine production and ototoxicity.
A 7-year-old boy presented with hematochezia and abdominal pain. A 3.7-cm-sized mass was identified in the ascending colon by abdominal computed tomography and colonoscopy. The patient underwent surgical resection. Pathological examination revealed a low-grade perivascular epithelioid cell tumor (PEComa). PEComa in the colon is very rare. Only a few cases have been reported so far. An effective treatment method for this rare tumor has not been established yet. The patient received adjuvant interferon-α immunotherapy for 1 year. He has been tumor-free for 26 months since the initial diagnosis. This report is the first documented case of the use of interferon-α for pediatric PEComa of the colon.
PurposeTo evaluate patients who underwent surgical or endovascular treatment after vascular injury related to posterior lumbar disc surgery.Materials and MethodsWe retrospectively reviewed seven cases of vascular injuries (four lacerations, one arteriovenous fistula [AVF], and two pseudoaneurysms) related to lumbar disc surgery by a posterior approach from January 1997 to December 2016 at Chonnam National University Hospital. Information of patient characteristics, diagnosis, treatment strategies, and outcomes were analyzed.ResultsFive out of seven cases were inhospital cases. In three laceration cases, each patient instantly became hypotensive and a life-threatening arterial injury was suspected. Therefore, the patient was immediately turned to the supine position and surgical repair was performed. The patients with pseudoaneurysm and AVF were treated by endovascular intervention. Remaining two were referred cases under the impression of vascular injuries. One laceration case of them was in preshock condition, and the left common iliac artery was surgically repaired. The other referred patient showed pseudoaneurysm which was treated with stent graft insertion. There was no surgery or endovascular intervention related death and none of the patients suffered any sequela related to vascular injury.ConclusionVascular injury associated with posterior lumbar disc surgery is not common, but can be fatal. Early recognition, diagnosis, and prompt treatment are essential to prevent fatal outcomes. Recently, endovascular intervention is increasingly and preferably used because of its low morbidity and mortality. However surgery is still the best option for the patients with unstable vital sign and endovascular approach can be applied to stable patients.
Domino kidney paired donation (KPD) is a method by which an altruistic living nondirected donor (LND) isOne-year and 5-year graft survival rates were 98.3% and 87.7%, respectively, with a median followup of 46 months. One-year and 5-year patient survival rates were 97.2% and 90.8%, respectively. In conclusion, multicenter domino KPD could multiply the benefits of donation from LNDs, with patients and graft survival rates comparable to those seen with conventional KPD.
There has been a significant growth in the number of deceased donors in Korea since the appropriate deceased organ donation system was launched. A comprehensive national program is required to improve deceased donation and achieve self-sufficiency.
Apoptotic signal pathways are delivered to caspase-3, caspase-9, or both in different cells via the death receptor pathway, mitochondrial pathway, or by the endoplasmic reticulum (ER) pathway through initiators of caspase-3, -8, -9, or -12. Tacrolimus (Tac)-induced apoptosis was characterized by nuclear fragmentation and caspase-3 activation. We examined the effect of tacrolimus on ER-derived calcium and caspase-3,-12-mediated apoptosis on Jurkat human T lymphocyte. Tac decreased the viability of Jurkat cells in a dose-dependent manner. Tac also increased continuously intracellular concentration of calcium from 24 hours to 72 hours. We did not find intracellular calcium changes on the treatment of calcium ionorpore (A23187) regardless of 1 nmol/L Tac concentration level. However, calcium adenosine triphosphatase inhibitor (thapsigargin) increased intracellular calcium accumulation and co-treating 1 nmol/L Tac further induced intracellular calcium accumulation. Interestingly, we found that 1 nmol/L Tac treatment induced activation of caspase-12 protease as well as the catalytic activity of caspase-3 but not catalytic activation of caspase-6, -8, and -9 proteases in Jurkat cells. These data advance our understanding of Tac-induced apoptosis is ER-derived calcium and caspases-3,-12- mediated apoptosis in human Jurkat cell line.
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