不明原因发热（fever of unknown origin，FUO或FOU）是临床常见的内科疑难病症。国内学者提出FUO的诊断标准是：发热期限超过2～3周，体温〉38．5℃，经过完整的病史询问、体格检查以及常规实验室检查，不能明确诊断者。据国内外大量...不明原因发热（fever of unknown origin，FUO或FOU）是临床常见的内科疑难病症。国内学者提出FUO的诊断标准是：发热期限超过2～3周，体温〉38．5℃，经过完整的病史询问、体格检查以及常规实验室检查，不能明确诊断者。据国内外大量病例分析，有关FUO的病因报道比例相仿，即感染性疾病占40％～50％，结缔组织病占15％左右，恶性肿瘤占20％～30％，而其中淋巴瘤是引起FUO最常见的恶性肿瘤，展开更多
本研究从DNA双链断裂同源重组修复角度探讨UNC13D(秀丽新小杆线虫)基因参与Ⅲ型家族性噬血细胞性淋巴组织细胞增生症(familial hemophagocytic lymphohistiocytosis type 3,FHL3)的发病机制。利用DNA同源重组修复方法,检测正常对照组及U...本研究从DNA双链断裂同源重组修复角度探讨UNC13D(秀丽新小杆线虫)基因参与Ⅲ型家族性噬血细胞性淋巴组织细胞增生症(familial hemophagocytic lymphohistiocytosis type 3,FHL3)的发病机制。利用DNA同源重组修复方法,检测正常对照组及UNC13D基因下调后DR-U2OS细胞同源重组修复率的变化情况,并研究此基因的相关功能。结果表明:下调DR-U2OS细胞的UNC13D基因表达后,同源重组修复率较正常对照组明显下降,且差异有统计学意义(P<0.05),提示UNC13D编码蛋白Munc13-4不仅参与到细胞毒颗粒的胞吐过程中,而且在DNA双链断裂修复中也起作用。结论:UNC13D基因突变可能通过抑制细胞毒颗粒的胞吐和降低DNA双链断裂后的同源重组修复率参与FHL3发病过程,这一研究结果为揭示FHL3的发病机制提供新的理论基础。展开更多
A 44- day- old male infant with familial hemophagocytic lymphohistiocytosis (FHL) associated with the MUNC13- 4 mutation is reported. He presented with fever and poor feeding, lymphocytosis with thrombocytopenia and C...A 44- day- old male infant with familial hemophagocytic lymphohistiocytosis (FHL) associated with the MUNC13- 4 mutation is reported. He presented with fever and poor feeding, lymphocytosis with thrombocytopenia and CSF pleocytosis without virological explanation. On the basis of progressive hyperferritinemia (1.323 ng/ml), anemia (hemoglobin: 5.2 g/dl), hypertriglyceridemia (547 mg/dl) and increased LDH (1063 IU/l) with hemophagocytosis in the bone marrow, hemophagocytic lymphohistiocytosis was diagnosed. He showed a good response to corticosteroid therapy and the disease was stable for more than 5 months. Thereafter, he suffered from central nervous system complications, and successfully underwent unrelated cord blood stem cell transplantation. A remission was observed for more than 2 years, with mild mental retardation. Genetic analysis revealed that he had a compound heterozygous mutation of MUNC13- 4; namely a novel 2163G > A mutation resulting in W721X, and 754- 1G > C resulting in a premature stop codon in this gene. Western blot analysis showed the complete loss of the MUNC13- 4 protein, whereas other molecules associated with the SNARE systems were detected at normal levels. Conclusion. FHL may have a broad clinical spectrum, and further analysis on its phenotype- genotype association is required to establish an appropriate treatment strategy, including immunochemotherapy and stem cell transplantation in the future.展开更多
文摘不明原因发热（fever of unknown origin，FUO或FOU）是临床常见的内科疑难病症。国内学者提出FUO的诊断标准是：发热期限超过2～3周，体温〉38．5℃，经过完整的病史询问、体格检查以及常规实验室检查，不能明确诊断者。据国内外大量病例分析，有关FUO的病因报道比例相仿，即感染性疾病占40％～50％，结缔组织病占15％左右，恶性肿瘤占20％～30％，而其中淋巴瘤是引起FUO最常见的恶性肿瘤，
文摘本研究从DNA双链断裂同源重组修复角度探讨UNC13D(秀丽新小杆线虫)基因参与Ⅲ型家族性噬血细胞性淋巴组织细胞增生症(familial hemophagocytic lymphohistiocytosis type 3,FHL3)的发病机制。利用DNA同源重组修复方法,检测正常对照组及UNC13D基因下调后DR-U2OS细胞同源重组修复率的变化情况,并研究此基因的相关功能。结果表明:下调DR-U2OS细胞的UNC13D基因表达后,同源重组修复率较正常对照组明显下降,且差异有统计学意义(P<0.05),提示UNC13D编码蛋白Munc13-4不仅参与到细胞毒颗粒的胞吐过程中,而且在DNA双链断裂修复中也起作用。结论:UNC13D基因突变可能通过抑制细胞毒颗粒的胞吐和降低DNA双链断裂后的同源重组修复率参与FHL3发病过程,这一研究结果为揭示FHL3的发病机制提供新的理论基础。
文摘A 44- day- old male infant with familial hemophagocytic lymphohistiocytosis (FHL) associated with the MUNC13- 4 mutation is reported. He presented with fever and poor feeding, lymphocytosis with thrombocytopenia and CSF pleocytosis without virological explanation. On the basis of progressive hyperferritinemia (1.323 ng/ml), anemia (hemoglobin: 5.2 g/dl), hypertriglyceridemia (547 mg/dl) and increased LDH (1063 IU/l) with hemophagocytosis in the bone marrow, hemophagocytic lymphohistiocytosis was diagnosed. He showed a good response to corticosteroid therapy and the disease was stable for more than 5 months. Thereafter, he suffered from central nervous system complications, and successfully underwent unrelated cord blood stem cell transplantation. A remission was observed for more than 2 years, with mild mental retardation. Genetic analysis revealed that he had a compound heterozygous mutation of MUNC13- 4; namely a novel 2163G > A mutation resulting in W721X, and 754- 1G > C resulting in a premature stop codon in this gene. Western blot analysis showed the complete loss of the MUNC13- 4 protein, whereas other molecules associated with the SNARE systems were detected at normal levels. Conclusion. FHL may have a broad clinical spectrum, and further analysis on its phenotype- genotype association is required to establish an appropriate treatment strategy, including immunochemotherapy and stem cell transplantation in the future.
