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.     

Hemoglobin Ohio (beta 142 Ala replaced by): a new abnormal hemoglobin with high oxygen affinity and erythrocytosis

Hemoglobin Ohio [beta 142 (H20) Ala replaced by Asp] was found in three members of a white family, all of whom showed erythrocytosis. The variant hemoglobin has a high oxygen affinity, a reduced Bohr effect, and diminished cooperativity. The functional abnormalities of Hb Ohio are explained by the proximity of the substituent beta 142 residue, both to beta 143 His, which is involved in the DPG binding site of hemoglobin, and to the critical C terminal region of the beta chain, which participates in the stabilization of the deoxy (T) conformation.     

Pseudo-Bernard-Soulier syndrome: thrombocytopenia caused by autoantibody to platelet glycoprotein Ib

The Bernard-Soulier syndrome is an inherited bleeding disorder that is due to a deficiency in platelet glycoprotein Ib. Bernard-Soulier platelets fail to agglutinate in response to ristocetin despite normal levels of factor VIII:von Willebrand factor. We report a patient who developed severe refractory thrombocytopenia postsurgically while receiving procainamide therapy. Thrombocytopenia was immune mediated since the patient's platelets bore high levels of antiplatelet antibody. Radioimmunoprecipitation studies demonstrated that the autoantibodies had specificity for platelet glycoproteins Ib and V as well as platelet HLA. The patient's plasma as well as purified immunoglobulin G completely inhibited the ristocetin-induced aggregation of normal platelets but did not inhibit adenosine diphosphate-induced aggregation. The laboratory studies revealed that this patient suffered from antibody-mediated thrombocytopenia with unusual characteristics that we have called pseudo-Bernard-Soulier syndrome.     

胰岛素在严重烧伤大鼠急性肺损伤中的保护作用

目的:观察胰岛素对严重烧伤所致的急性肺损伤的保护效应。方法:实验于2006-01/08在解放军第四军医大学西京医院全军烧伤中心实验室完成。取成年雄性SD大鼠36只,随机分成3组,每组12只:①烫伤 胰岛素组:水浴锅94℃,20s,制备30%总体表面积全层皮肤烫伤模型,伤后即刻腹腔注射生理盐水40mL/kg,并皮下注射胰岛素3U/kg。②烫伤组:造模和腹腔注射同烫伤 胰岛素组,皮下注射等体积生理盐水。③假烫组:用室温水浴模拟烫伤过程,伤后不给予补液。烫伤24h后,收集动脉血测定超氧化物歧化酶活性,收集支气管肺泡灌洗液测定蛋白含量,取肺组织进行苏木精-伊红染色观察病理变化,并测定髓过氧化物酶活性,同时电镜观察胸主动脉血管内皮细胞变化情况。结果:36只大鼠进入结果分析。①肺病理变化:烫伤 胰岛素组肺脏渗出和水肿较烫伤组明显减轻。②肺泡灌洗液中蛋白的质量浓度:烫伤组和烫伤 胰岛素组高于假烫组[(702.9±169.5),(486.5±149.2),(240.5±140.7)mg/L,P<0.05],烫伤 胰岛素组低于烫伤组(P<0.05)。③肺脏髓过氧化物酶活性:烫伤 胰岛素组低于烫伤组[(36.01±8.17),(59.51±12.50)nkat/g,P<0.05],与假烫组比较差异不显著。④血清超氧化物歧化酶活性:烫伤组和烫伤 胰岛素组低于假烫组[(2.27±0.18),(2.63±0.19),(2.81±0.21)mkat/L,P<0.01,0.05],烫伤 胰岛素组高于烫伤组(P<0.01)。⑤电镜下可见烫伤 胰岛素组内皮细胞损伤较烫伤组轻。结论:严重烧伤早期外源性胰岛素干预后可减轻急性肺损伤,具有明显的肺脏保护作用,这种作用可能与胰岛素的内皮细胞保护效应有关。