74例血友病B患者FⅨ基因突变研究

目的 研究导致中国人血友病B的凝血因子Ⅸ（FⅨ）基因突变类型的分布,并比较与美国白种人群有何异同。方法 从患者外周血白细胞抽提基因组DNA,分9段扩增Ⅸ基因外显子序列,用基因扩增转录测序技术直接测序法检出突变。结果 74例患者中有69例查到了FⅨ基因58种突变。分析比较这69例患者FⅨ基因突变类型的分布特征与美国白种人无显著性。中国不同地区之间差异也无显著性。结论 中国人血友病B的FⅨ基因突变类型非常分散,呈高度异质性。与美国白种人之间相比差异无显著性。     

High-intensity focused ultrasound extracorporeal ablation of liver tissues in rabbits

ＨｉｇｈｉｎｔｅｎｓｉｔｙｆｏｃｕｓｅｄｕｌｔｒａｓｏｕｎｄｅｘｔｒａｃｏｒｐｏｒｅａｌａｂｌａｔｉｏｎｏｆｌｉｖｅｒｔｉｓｓｕｅｓｉｎｒａｂｂｉｔｓＣＨＥＮＧＳｈｕＱｕｎ１，ＺＨＯＵＸｉｎＤａ１，ＴＡＮＧＺｈａｏＹｏｕ１，ＹＵＹａｏ１，Ｂ...     

Decreased levels of total and reduced glutathione in CD4+ lymphocytes in common variable immunodeficiency are associated with activation of the tumor necrosis factor system: possible immunopathogenic role of oxidative stress

We have previously shown chronic immune activation and enhanced generation of reactive oxygen species in common variable immunodeficiency (CVI). In the present study, we examined levels of glutathione, the dominant intracellular thiol, that play an important protective role against oxidative and inflammatory stress in plasma and in monocytes and lymphocyte subsets in 20 CVI patients and in 16 healthy controls. CD4+ lymphocytes from CVI patients had significantly lower levels of both total and reduced glutathione as well as a lower ratio of reduced to total glutathione compared with healthy controls. This decrease in glutathione levels in CD4+ lymphocytes was most pronounced in the CD45RA+ subset. Plasma levels of total glutathione were also significantly decreased in CVI. In contrast, monocytes from CVI patients exhibited increased levels of both total and reduced glutathione compared with blood donor monocytes. CVI patients had significantly raised serum levels of tumor necrosis factor alpha (TNF alpha) and TNF alpha concentration was strongly associated with glutathione depletion in CD4+ lymphocytes. Furthermore, the lowest levels of both total and reduced glutathione were found in a subgroup of CVI patients characterized by persistent immune activation in vivo, decreased numbers of CD4+ lymphocytes in peripheral blood, and splenomegaly. Finally, supplementation of cell cultures with glutathione-monoethyl ester did significantly enhance interleukin-2 production from peripheral blood mononuclear cells in CVI patients. These glutathione abnormalities in CVI indicate increased oxidative stress, particularly in CD4+ lymphocytes, and intracellular depletion of reduced glutathione of the demonstrated magnitude may have profound implications for CD4+ lymphocyte function and the immunodeficiency in CVI.     

Factor VIII gene inversions in severe hemophilia A: results of an international consortium study

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells were observed among 225 cases (approximately 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).     

Interferon-alpha alters spectrin organization in normal and leukemic human B lymphocytes

Interferon-alpha (IFN-alpha) regulates the growth, differentiation, and recirculation of normal and malignant B lymphocytes. In this report we examine the effects of IFN-alpha on the distribution of the cytoskeletal protein spectrin in peripheral blood B lymphocytes from normal donors and patients diagnosed with chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL). Exposure of normal and leukemic B cells to IFN-alpha in vitro was shown by immunofluorescence microscopy to cause a dose-dependent increase in the percentage of cells containing discrete focal accumulations of spectrin, ie, a single large aggregate or cap-like structure near the plasma membrane. Although the magnitude of this effect was variable among individual patient samples, in some experiments IFN-alpha induced a fourfold increase in the percentage of leukemic B cells exhibiting focal accumulations of spectrin. Spectrin reorganization induced by IFN-alpha was abrogated by the protein synthesis inhibitor cycloheximide. In addition, IFN-alpha increased the total cellular content of spectrin in B-CLL cells by approximately twofold to fourfold. Finally, a role for protein kinase C in mediating the effects of IFN-alpha on spectrin's organization is implicated by studies in which calphostin C inhibited the IFN-induced focal accumulation of spectrin. Taken together, these studies suggest that the immunomodulatory activities of IFN-alpha in normal and malignant B cells involve a change in the organization of the spectrin- based cytoskeleton.     

Molecular characterization of a novel form of (A gamma delta beta)zero thalassemia deletion in a Chinese family

We have identified and molecularly characterized a novel deletion in the beta-globin gene cluster that is associated with elevated fetal hemoglobin in the adult. The propositus is a homozygote from the Yunnan province of China. The deletion spans about 90 kb of DNA and removes the A gamma, delta, and beta-globin genes. The 5' breakpoint of the deletion is located about 0.13 kb upstream from the A gamma-globin gene, whereas the 3' breakpoint is located about 66 kb downstream from the beta-globin gene, about 13 kb upstream from the breakpoint of the Chinese (A gamma delta beta)zero-thalassemia. Heterozygotes for this Yunnanese form of (A gamma delta beta)zero-thalassemia express between 9% and 17% of fetal hemoglobin, whereas the homozygote present with a mild anemia (Hb = 10.7 g/dl). Comparison of the sites of 3' breakpoints of the Yunnanese and the Chinese (A gamma delta beta)zero-thalassemia mutants is compatible with the hypothesis that an enhancer element is located between the 3' breakpoints of these two mutants. Juxta-position to the G gamma gene of this element may be responsible for the efficient gamma-gene expression in the Yunnanese mutant.     

Incidental diagnosis of a rare endobronchial schwannoma in a 7-year-old girl: A case report

Schwannomas are nerve sheath tumors that arise from Schwann cells and are mainly benign. The likelihood of endobronchial schwannoma amongst all intrapulmonary tumors is up to 0.2% and mainly presents late. This study described a pediatric endobronchial schwannomas case discovered incidentally during rigid bronchoscopy. This case is uncommon, and its report can help physicians diagnose the same cases. The case was a 7-year-old girl presenting with fever and cough who had no history of pulmonary disease or relevant family history. Physical examination, chest radiography, CT scan, and bronchoscopy were performed on the patient. A biopsy was taken from the observed mass obstructing the bronchus during bronchoscopy. The mass was resected. Pathology revealed low-grade spindle cell neoplasm and confirmed schwannoma in immunohistochemistry. Endobronchial schwannomas can happen in children presenting with simple symptoms. For benign lesions, the prognosis is generally good. Due to the slow growth of these tumors and the potential for recurrence after resection, long-term follow-up may be needed.