Heterogeneity of drug-dependent platelet antigens and their antibodies in quinine- and quinidine-induced thrombocytopenia: involvement of glycoproteins Ib, IIb, IIIa, and IX

The molecular nature of platelet receptors for quinine- and quinidine- dependent antiplatelet antibodies (Q.Ab and Qd.Ab) was studied by immunoblotting. One Q.Ab caused quinine-dependent IgG binding to platelet proteins with molecular weights (mol wts) of 174 Kd and 93 Kd and another to only a 93-Kd protein. A third Q.Ab caused binding to 174- , 140-, 93-, and 57-Kd proteins, while a fourth Q.Ab and a Qd.Ab caused IgG binding to 174- and 18-Kd proteins. Using platelets from patients with Glanzmann's thrombasthenia or Bernard Soulier syndrome and purified GPIIIa, these proteins were shown to be GPIb, GPIIb, GPIIIa, GPIX, and an unidentified 57-Kd protein missing in Bernard Soulier syndrome. Binding to the 93-Kd protein was independent of the PIA1 antigen. Absorption of one Q.Ab with Glanzmann's thrombasthenia platelets revealed different populations of antibodies with different specificities within the one patient. Thus Q.Ab and Qd.Ab are heterogeneous and may be directed toward different epitopes on major platelet glycoproteins.     

Association of the expression of an SR-cyclophilin with myeloid cell differentiation

The role of a 150-kD SR-cyclophilin (NK-TR1) in monocyte differentiation was investigated. Using an antipeptide monoclonal antibody, we have detected NK-TR1 in human peripheral blood monocytes and HL-60 cells. Unstimulated monocytes showed a low intracellular level of NK-TR1 protein that increased over 3 days of lipopolysaccharide + interferon-gamma treatment, consistent with the kinetics of monocyte differentiation. Normal HL-60 cells also had a low level of NK-TR1 protein, and exposure to 1.25% dimethyl sulfoxide (DMSO) resulted in a marked transient increase in expression that returned to basal levels before the development of granulocyte differentiation-associated biochemical changes. Phorbol myristate acetate, a promoter of monocytic differentiation in HL-60 cells, also caused a significant increase in NK-TR1 over basal levels. Transfection of a vector expressing NK-TR1 antisense RNA into HL-60 cells suppressed DMSO-mediated growth arrest. In addition, the development of a more mature phenotype, as measured by expression of CD16, and the ability to reduce nitroblue tetrazoleum dye was inhibited in transfectants when compared with controls. These results are consistent with the hypothesis that the NK-TR1 gene product is required for the progression towards a mature differentiated phenotype.     

维拉帕米对大鼠肝脏贮脂细胞增殖及胶原基因表达的影响

在肝纤维化的发生发展过程中，细胞外基质的过度合成和异常沉积是最主要的病理过程。研究表明，病理状态下，贮脂细胞（ＦＳＣ）被激活，数量增多，分泌大量的胶原等细胞外基质，导致肝纤维化的发生、发展［１］。材料和方法一、实验动物雄性ＳＤ大鼠１０只，其中５只皮下注射４０％ＣＣｌ４茶油溶液建立肝纤维化模型。二、试剂链霉蛋白酶和Ｎｙｃｏｄｅｎｚ购于Ｓｉｇｍａ公司；胶原酶购于上海医工院；维拉帕米（Ｖｅｒ）购于Ｋｎｏｌｌ公司；ＲＮＡ提取剂、Ｐ３２ｄＣＴＰ、随机引物标记试剂盒购于Ｇｉｂｃｏ、亚辉、Ｐｒｏｍｅｇａ公司三…     

应用弹性测量仪和超声波评价烧伤后增生瘢痕的粘弹性

目的：研究应用弹性测量仪和超声波测量评价烧伤后增生瘢痕的变化。方法：自1995年1月起，长期随访18例随机选择的烧伤患者（年龄为1－60岁），应用皮肤弹性测量仪及超声波影像对患者每月测量一次皮肤在负压吸引作用下的最大变形度（R0）和粘弹性指数（R8），比较增生瘢痕与身体对侧相应部位测量的区别，并将检查结果与传统临床分度方法进行比较分析。同时也对皮肤弹性值与临床观察的瘢痕硬度进行相关性分析。结果：烧伤后增生瘢痕的R8＞0．193时，临床硬度分度也较高（9％为0度，14％为1度，30％为2度，46％为3度，83％为4度）。结论：R8＞1．93被定为预后数值，大于该数值者需要密切随访。     

纳米银医用抗菌敷料在小儿泌尿外科手术创面的应用特点

目的:阴茎包皮系神经末梢最敏感部位之一,观察纳米银医用抗菌敷料用于包皮手术后创面的止痛防粘连效果,并与普通凡士林油纱相比较。方法:选择解放军总医院小儿外科2006-01/08收治住院手术的包茎、包皮过长、尿道下裂患儿220例,随机分为纳米银敷料组和对照组各110例。纳米银敷料组患儿术后创面覆盖以无菌生理盐水打湿后的纳米银医用抗菌敷料,对照组使用普通凡士林油纱包扎伤口,术后第3,5,7天换药。比较两组患儿术后第1,3,5,7天的疼痛感受及创面愈合情况。结果:220例患儿均进入结果分析。纳米银敷料组术后第1,3,5天疼痛较对照组轻(P<0.01);且纳米银敷料比普通油纱更容易从创面分离,换药所需时间短,换药过程不会引起创面渗血和患儿疼痛;术后第5天纳米银敷料组创面面积小于对照组(P=0.041);两组均未发现材料宿主反应。结论:纳米银医用抗菌敷料用于包皮的换药具有明确的防粘连、促进创面愈合、止痛的作用,其效果优于普通凡士林油纱。     

Lack of transmission of neutrophil and platelet antibodies by intravenous immunoglobulin in bone marrow transplant patients

BACKGROUND: Several studies have demonstrated that the administration of intravenous immunoglobulin (IVIG) may be followed by the transient appearance of positive red cell antibody screens, positive direct antiglobulin tests, and, occasionally, frank hemolysis. However, little information is available regarding the possibility that IVIG could transmit neutrophil and/or platelet antibodies. STUDY DESIGN AND METHODS: Serum samples were obtained both immediately before and immediately after the administration of 12 separate lots of commercially available IVIG to bone marrow transplant patients. RESULTS: None of the patients were shown by standard granulocyte immunofluorescence testing to have acquired neutrophil antibodies. Four of the 12 postinfusion sera were positive for platelet antibodies in standard platelet suspension immunofluorescence testing, but in all four instances the corresponding preinfusion serum was positive as well. CONCLUSION: The risk of acquiring neutrophil and/or platelet antibodies after the administration of commercially available IVIG appears to be low.     

高龄供者非清髓性异基因造血干细胞移植后低剂量环孢素A治疗老年急性白血病1例

目的:分析高龄供者非清髓性外周血造血干细胞移植治疗老年急性白血病后,采用低剂量环孢素A免疫治疗方案的疗效。方法:选择2005-11-15广州市第一人民医院收治患者1例,男,57岁,诊断为急性非淋巴细胞白血病-M5a。患者知情同意并签署知情同意书。移植前经过化疗达到完全缓解,合并2型糖尿病、肝功能不良、慢性心脏供血不足。供者为患者同胞姐姐,64岁,HLA全相合,血型相同。干预措施:①预处理用药包括氟达拉滨、马利兰针剂和环磷酰胺。于移植前第4～9天氟达拉滨30mg/(m2.d);移植前第3,4天马利兰针0.8mg/kg,Q6h;移植前第1,2天环磷酰胺60mg/(kg.d)。②移植物抗宿主病预防用环孢素A和氨甲蝶呤,形成供者嵌合体后,采用低剂量环孢素A。③移植后并发症防治和支持治疗:更昔洛韦防治巨细胞病毒感染、前列腺素E1防治肝静脉闭塞病、移植后1d予粒细胞集落刺激因子5μg/(kg.d),Hb<70g/L和PLT<20×109L-1时输注红细胞和血小板。④供者采用粒细胞集落刺激因子动员,150μg/d,皮下注射,12h1次,连用5d,第4,5天采集外周血造血干细胞,于第5天一同输注给患者。结果:①移植后患者造血及免疫重建情况:移植后早期获得造血重建,20d时中性粒细胞>0.5×109L-1,18d时血小板>20×109L-1。自然杀伤细胞、CD3 T淋巴细胞和CD3 CD8 数恢复、CD19 B淋巴细胞和CD3 CD4 分别在移植后2,6,14个月恢复。②植入证据:移植后4周,经过DNA短串联重复序列多态性和XX/XY染色体的荧光原位杂交分析证明为供者型完全嵌合体。③移植后并发症:移植过程顺利,无严重感染,未出现急性移植物抗宿主病。移植后112d,出现腹泻、四肢和面部出现红色斑丘疹,伴有感觉功能异常,移植后6个月出现中耳积液、突发性耳聋,经过环孢素A剂量治疗控制至12个月停药。随访14个月,生活正常。结论:采用以氟达拉滨为基础的非清髓性、高龄同胞供者外周血造血干细胞移植治疗有多种合并症老年急性白血病,植入后采用低剂量环孢素A治疗是一种有效安全的方法。     

Use of a BamHI polymorphism in the factor IX gene for the determination of hemophilia B carrier status

A BamHI polymorphism has been identified in the human factor IX gene. This polymorphism, which occurs in approximately 6% of X chromosomes, has been used to determine the carrier status of a female in a family with a history of hemophilia B. This family was uninformative for the previously reported TaqI and Xmnl polymorphisms in the factor IX gene.     

Interleukin-12 induces tyrosine phosphorylation and activation of 44-kD mitogen-activated protein kinase in human T cells

Interleukin-12 (IL-12) is a novel cytokine that enhances numerous functional activities of human T cells and natural killer (NK) cells. The present studies were undertaken to characterize some of the early signaling events following IL-12 stimulation of mitogen-activated normal T cells. In these cells, IL-12 induces rapid tyrosine phosphorylation of proteins of 21, 44, and 54 kD. However, IL-12 does not induce tyrosine phosphorylation in normal resting T cells. In conjunction with increased tyrosine phosphorylation of several substrates, IL-12 stimulation resulted in increased in vitro kinase activity of immunoprecipitated tyrosine phosphorylated proteins. The 44- kD protein has been characterized as one isoform of the mitogen- activated protein (MAP) kinase family. Increased tyrosine phosphorylation of MAP kinase following IL-12 stimulation was also associated with enhanced enzymatic activity of this protein in vitro as measured by myelin basic protein phosphotransferase assay. These studies identify MAP kinase as one of the intracellular elements of the IL-12 signaling pathway in human T cells.     

Type beta transforming growth factor is a potent inhibitor of murine megakaryocytopoiesis in vitro

To investigate the potential role of platelets in the inhibition of megakaryocytopoiesis, freeze-thawed extracts of human platelets were added to serumless liquid cultures of murine marrow. When acetylcholinesterase (AchE), a marker of megakaryocytic differentiation in mice, was assayed, a significant inhibition of enzymatic activity was noted in cultures containing the equivalent of greater than 5 X 10(6) solubilized platelets per milliliter. Freeze-thawed extracts of granulocytes had significantly less inhibitory effect than did platelets. Transforming growth factor beta (TGF-beta), a growth factor known to be inhibitory to some cell lineages and to be found at relatively high concentrations in platelets, was then added to liquid marrow cultures. A similar inhibition of AchE activity was detected when cultures were stimulated with mitogen-stimulated conditioned medium. The effect was potent with 50% inhibition of AchE activity observed at 4 pmol TGF-beta/L. To determine if TGF-beta inhibited specifically one aspect of megakaryocytic differentiation, the factor was added to isolated single megakaryocytes in serumless culture induced by interleukin 3 (IL3) to increase in size. The number of megakaryocytes increasing in size in response to IL 3 exposure was reduced from 68% to 20% when both factors were simultaneously added to cultures. Colony assays showed that megakaryocytic and granulocyte- macrophage colony detection was inhibited at picomolar concentrations of the factor. These data suggest that TGF-beta is a potent in vitro inhibitor of the murine megakaryocytic lineage, although its effects are not limited to this lineage.