BACKGROUND Osteomalacia(OM)is frequently confused with various musculoskeletal or other rheumatic diseases,especially in patients with adult-onset widespread musculoskeletal pain because of its low prevalence and non-...BACKGROUND Osteomalacia(OM)is frequently confused with various musculoskeletal or other rheumatic diseases,especially in patients with adult-onset widespread musculoskeletal pain because of its low prevalence and non-specific manifestations.AIM To facilitate the early diagnosis and etiology-specific treatment of adult-onset hypophosphatemic OM.METHODS A retrospective review of medical records was performed to screen adult patients who visited a physiatry locomotive medicine clinic(spine and musculoskeletal pain clinic)primarily presenting with widespread musculoskeletal pain at a single tertiary hospital between January 2011 and December 2019.We enrolled patients with hypophosphatemia,high serum bone-specific alkaline phosphatase levels,and at least one imaging finding suggestive of OM.RESULTS Eight patients with adult-onset hypophosphatemic OM were included.The back was the most common site of pain.Proximal dominant symmetric muscle weakness was observed in more than half of the patients.Bone scintigraphy was the most useful imaging modality for diagnosing OM because radiotracer uptake in OM showed characteristic patterns.Six patients were diagnosed with adefovir(ADV)-induced Fanconi syndrome,and the other two patients were diagnosed with tumor-induced OM and light-chain nephropathy,respectively.After phosphorus and vitamin D supplementation and treatment for the underlying etiologies,improvements in pain,muscle strength,and gait were observed in all patients.CONCLUSION Mechanical pain characteristics,hypophosphatemia,and distinctive bone scintigraphy patterns are the initial diagnostic indicators of adult-onset hypophosphatemic OM.ADV-induced Fanconi syndrome is the most common etiology of hypophosphatemic OM in hepatitis B virus-endemic countries.展开更多
BACKGROUND The Hippo signaling pathway regulates organ size by regulating cell proliferation and apoptosis with terminal effectors including Yes-associated protein-1(YAP-1).Dysregulation in Hippo pathway has been prop...BACKGROUND The Hippo signaling pathway regulates organ size by regulating cell proliferation and apoptosis with terminal effectors including Yes-associated protein-1(YAP-1).Dysregulation in Hippo pathway has been proposed as one of the therapeutic targets in hepatocarcinogenesis.The levels of reactive oxygen species(ROS)increase during the progression from early to advanced hepatocellular carcinoma(HCC).AIM To study the activation of YAP-1 by ROS-induced damage in HCC and the involved signaling pathway.METHODS The expression of YAP-1 in HCC cells(Huh-7,HepG2,and SNU-761)was quantified using real-time polymerase chain reaction and immunoblotting.Human HCC cells were treated with H2O2,which is a major component of ROS in living organisms,and with either YAP-1 small interfering RNA(siRNA)or control siRNA.To investigate the role of YAP-1 in HCC cells under oxidative stress,MTS assays were performed.Immunoblotting was performed to evaluate the signaling pathway responsible for the activation of YAP-1.Eighty-eight surgically resected frozen HCC tissue samples and 88 nontumor liver tissue samples were used for gene expression analyses.RESULTS H2O2 treatment increased the mRNA and protein expression of YAP-1 in HCC cells(Huh-7,HepG2,and SNU-761).Suppression of YAP-1 using siRNA transfection resulted in a significant decrease in tumor proliferation during H2O2 treatment both in vitro and in vivo(both P<0.05).The oncogenic action of YAP-1 occurred via the activation of the c-Myc pathway,leading to the upregulation of components of the unfolded protein response(UPR),including 78-kDa glucoseregulated protein and activating transcription factor-6(ATF-6).The YAP-1 mRNA levels in human HCC tissues were upregulated by 2.6-fold compared with those in nontumor tissues(P<0.05)and were positively correlated with the ATF-6 Levels(Pearson’s coefficient=0.299;P<0.05).CONCLUSION This study shows a novel connection between YAP-1 and the UPR through the c-Myc pathway during oxidative stress in HCC.The ROS-induced activation of YAP-1 via the c-Myc pathway,which leads to the activation of the UPR pathway,might be a therapeutic target in HCC.展开更多
Purpose: To investigate the pathogenesis of a secondary iris cyst with an immunohistochemical method. Methods: Single observational case report. A pathologic specimen was obtained from a 5-year-old girl who was found ...Purpose: To investigate the pathogenesis of a secondary iris cyst with an immunohistochemical method. Methods: Single observational case report. A pathologic specimen was obtained from a 5-year-old girl who was found to have a secondary iris cyst. She had a history of previous penetrating ocular trauma and subsequent cataract surgery and pupilloplasty. Immunohistochemical staining with cytokeratin (CK) 19 and CK3 was used. Results: After immunohistochemical staining, the inner wall showed positive staining for CK19, which is specific for limbal, peripheral cornea and conjunctival epithelium, and negative staining for CK3, which is specific for corneal epithelium. Conclusions: With the aid of immunohistochemical analysis, a conjunctival epithelial origin was indicated, and pupilloplasty was identified as the causal event of the iris cyst while the possibility of primary iris cyst was ruled out.展开更多
基金This study was approved by the Institutional Review Board of Samsung Medical Center(approval number:2020-09-027-001).
文摘BACKGROUND Osteomalacia(OM)is frequently confused with various musculoskeletal or other rheumatic diseases,especially in patients with adult-onset widespread musculoskeletal pain because of its low prevalence and non-specific manifestations.AIM To facilitate the early diagnosis and etiology-specific treatment of adult-onset hypophosphatemic OM.METHODS A retrospective review of medical records was performed to screen adult patients who visited a physiatry locomotive medicine clinic(spine and musculoskeletal pain clinic)primarily presenting with widespread musculoskeletal pain at a single tertiary hospital between January 2011 and December 2019.We enrolled patients with hypophosphatemia,high serum bone-specific alkaline phosphatase levels,and at least one imaging finding suggestive of OM.RESULTS Eight patients with adult-onset hypophosphatemic OM were included.The back was the most common site of pain.Proximal dominant symmetric muscle weakness was observed in more than half of the patients.Bone scintigraphy was the most useful imaging modality for diagnosing OM because radiotracer uptake in OM showed characteristic patterns.Six patients were diagnosed with adefovir(ADV)-induced Fanconi syndrome,and the other two patients were diagnosed with tumor-induced OM and light-chain nephropathy,respectively.After phosphorus and vitamin D supplementation and treatment for the underlying etiologies,improvements in pain,muscle strength,and gait were observed in all patients.CONCLUSION Mechanical pain characteristics,hypophosphatemia,and distinctive bone scintigraphy patterns are the initial diagnostic indicators of adult-onset hypophosphatemic OM.ADV-induced Fanconi syndrome is the most common etiology of hypophosphatemic OM in hepatitis B virus-endemic countries.
文摘BACKGROUND The Hippo signaling pathway regulates organ size by regulating cell proliferation and apoptosis with terminal effectors including Yes-associated protein-1(YAP-1).Dysregulation in Hippo pathway has been proposed as one of the therapeutic targets in hepatocarcinogenesis.The levels of reactive oxygen species(ROS)increase during the progression from early to advanced hepatocellular carcinoma(HCC).AIM To study the activation of YAP-1 by ROS-induced damage in HCC and the involved signaling pathway.METHODS The expression of YAP-1 in HCC cells(Huh-7,HepG2,and SNU-761)was quantified using real-time polymerase chain reaction and immunoblotting.Human HCC cells were treated with H2O2,which is a major component of ROS in living organisms,and with either YAP-1 small interfering RNA(siRNA)or control siRNA.To investigate the role of YAP-1 in HCC cells under oxidative stress,MTS assays were performed.Immunoblotting was performed to evaluate the signaling pathway responsible for the activation of YAP-1.Eighty-eight surgically resected frozen HCC tissue samples and 88 nontumor liver tissue samples were used for gene expression analyses.RESULTS H2O2 treatment increased the mRNA and protein expression of YAP-1 in HCC cells(Huh-7,HepG2,and SNU-761).Suppression of YAP-1 using siRNA transfection resulted in a significant decrease in tumor proliferation during H2O2 treatment both in vitro and in vivo(both P<0.05).The oncogenic action of YAP-1 occurred via the activation of the c-Myc pathway,leading to the upregulation of components of the unfolded protein response(UPR),including 78-kDa glucoseregulated protein and activating transcription factor-6(ATF-6).The YAP-1 mRNA levels in human HCC tissues were upregulated by 2.6-fold compared with those in nontumor tissues(P<0.05)and were positively correlated with the ATF-6 Levels(Pearson’s coefficient=0.299;P<0.05).CONCLUSION This study shows a novel connection between YAP-1 and the UPR through the c-Myc pathway during oxidative stress in HCC.The ROS-induced activation of YAP-1 via the c-Myc pathway,which leads to the activation of the UPR pathway,might be a therapeutic target in HCC.
文摘Purpose: To investigate the pathogenesis of a secondary iris cyst with an immunohistochemical method. Methods: Single observational case report. A pathologic specimen was obtained from a 5-year-old girl who was found to have a secondary iris cyst. She had a history of previous penetrating ocular trauma and subsequent cataract surgery and pupilloplasty. Immunohistochemical staining with cytokeratin (CK) 19 and CK3 was used. Results: After immunohistochemical staining, the inner wall showed positive staining for CK19, which is specific for limbal, peripheral cornea and conjunctival epithelium, and negative staining for CK3, which is specific for corneal epithelium. Conclusions: With the aid of immunohistochemical analysis, a conjunctival epithelial origin was indicated, and pupilloplasty was identified as the causal event of the iris cyst while the possibility of primary iris cyst was ruled out.