To investigate whether reduced levels of plasma platelet-activating factor acetylhydrolase (PAF-AH) as a result of a genetic polymorphism are involved in the pathogenesis of Kawasaki disease (KD). Study design: The fr...To investigate whether reduced levels of plasma platelet-activating factor acetylhydrolase (PAF-AH) as a result of a genetic polymorphism are involved in the pathogenesis of Kawasaki disease (KD). Study design: The frequency of a V279F polymorphism (G/T transversion) in the PAF-AH gene was quantified in 76 Japanese children with KD and 112 healthy Japanese adults using the allele- specific polymerase chain reaction (PCR). Associations between genotype, clinical features, and resistance to intravenous immunoglobulin (IVIG) were investigated in the patients with KD. Plasma PAF-AH activity was measured by using [3H]- acetyl-PAF. Results: There were no significant differences in genotype frequency between patients and controls (P = .51). Compared with the GG (normal genotype) group, significantly more patients in the GT (heterozygous) + TT (homozygous deficient) group required additional IVIG (52% vs 14% , P = .001). The duration of fever and maximum serum C-reactive protein (CRP) levels also were significantly increased in the GT+ TT group (P = .012 and .036, respectively), whereas plasma PAF-AH activity was significantly lower (P < .0001). Conclusion: We conclude that the V279F polymorphism in the plasma PAF-AH gene and consequent enzymatic deficiency is one of the factors for IVIG nonresponse in Japanese patients with acute KD.展开更多
目的明确泛素特异性蛋白酶41(ubiguitin-specific peptidase 41,USP41)在三阴性乳腺癌(triple-negative breast cancer,TNBC)的表达情况,及其与TNBC恶性表型及阿霉素敏感性的相关性和潜在作用机制。方法采用Western blot、qPCR检测USP41...目的明确泛素特异性蛋白酶41(ubiguitin-specific peptidase 41,USP41)在三阴性乳腺癌(triple-negative breast cancer,TNBC)的表达情况,及其与TNBC恶性表型及阿霉素敏感性的相关性和潜在作用机制。方法采用Western blot、qPCR检测USP41在TNBC耐药细胞株及临床组织样本的表达情况。随后确定USP41分子高表达,并通过CCK8、克隆形成实验、Transwell、Western blot及CoIP-MS等细胞生物学方法评价USP41在TNBC恶性表型及阿霉素耐药中的作用及机制。结果USP41在TNBC样本的表达显著高于癌旁组织。USP41在阿霉素耐药细胞株MDA-MB-231/DXR中表达量高出近40倍,IC50值为6.86μM。干扰USP41可显著增加MDA-MB-231/DXR细胞对阿霉素的敏感性。干扰USP41可显著的抑制细胞的细胞增殖、克隆形成及迁移能力,克隆数量降低30%~80%,迁移细胞数量降低超过70%,差异有统计学意义。此外,USP41敲低可提高MDA-MB-231细胞对阿霉素的敏感性,IC50由5.49μM降低到2.36μM和2.56μM。CO-IP结果显示USP41可与活化的蛋白激酶C1受体(receptor of activated protein kinase C1,RACK1)直接相互作用,且RACK1在癌组织的表达显著高于癌旁。干扰RACK1可抑制MDA-MB-231细胞增殖,IC50由9.87μM降低到4.67μM和4.36μM。克隆形成能力下降超过30%,差异有统计学意义。相较于对照组,USP41敲减使细胞迁移能力下降超过70%。结论USP41高表达与TNBC恶性表型及阿霉素耐药相关,且RACK1可能是USP41发挥作用的关键分子。展开更多
文摘To investigate whether reduced levels of plasma platelet-activating factor acetylhydrolase (PAF-AH) as a result of a genetic polymorphism are involved in the pathogenesis of Kawasaki disease (KD). Study design: The frequency of a V279F polymorphism (G/T transversion) in the PAF-AH gene was quantified in 76 Japanese children with KD and 112 healthy Japanese adults using the allele- specific polymerase chain reaction (PCR). Associations between genotype, clinical features, and resistance to intravenous immunoglobulin (IVIG) were investigated in the patients with KD. Plasma PAF-AH activity was measured by using [3H]- acetyl-PAF. Results: There were no significant differences in genotype frequency between patients and controls (P = .51). Compared with the GG (normal genotype) group, significantly more patients in the GT (heterozygous) + TT (homozygous deficient) group required additional IVIG (52% vs 14% , P = .001). The duration of fever and maximum serum C-reactive protein (CRP) levels also were significantly increased in the GT+ TT group (P = .012 and .036, respectively), whereas plasma PAF-AH activity was significantly lower (P < .0001). Conclusion: We conclude that the V279F polymorphism in the plasma PAF-AH gene and consequent enzymatic deficiency is one of the factors for IVIG nonresponse in Japanese patients with acute KD.
文摘目的明确泛素特异性蛋白酶41(ubiguitin-specific peptidase 41,USP41)在三阴性乳腺癌(triple-negative breast cancer,TNBC)的表达情况,及其与TNBC恶性表型及阿霉素敏感性的相关性和潜在作用机制。方法采用Western blot、qPCR检测USP41在TNBC耐药细胞株及临床组织样本的表达情况。随后确定USP41分子高表达,并通过CCK8、克隆形成实验、Transwell、Western blot及CoIP-MS等细胞生物学方法评价USP41在TNBC恶性表型及阿霉素耐药中的作用及机制。结果USP41在TNBC样本的表达显著高于癌旁组织。USP41在阿霉素耐药细胞株MDA-MB-231/DXR中表达量高出近40倍,IC50值为6.86μM。干扰USP41可显著增加MDA-MB-231/DXR细胞对阿霉素的敏感性。干扰USP41可显著的抑制细胞的细胞增殖、克隆形成及迁移能力,克隆数量降低30%~80%,迁移细胞数量降低超过70%,差异有统计学意义。此外,USP41敲低可提高MDA-MB-231细胞对阿霉素的敏感性,IC50由5.49μM降低到2.36μM和2.56μM。CO-IP结果显示USP41可与活化的蛋白激酶C1受体(receptor of activated protein kinase C1,RACK1)直接相互作用,且RACK1在癌组织的表达显著高于癌旁。干扰RACK1可抑制MDA-MB-231细胞增殖,IC50由9.87μM降低到4.67μM和4.36μM。克隆形成能力下降超过30%,差异有统计学意义。相较于对照组,USP41敲减使细胞迁移能力下降超过70%。结论USP41高表达与TNBC恶性表型及阿霉素耐药相关,且RACK1可能是USP41发挥作用的关键分子。
