Monoclonal antibodies recognizing epitopes on the extracellular face and intracellular N-terminus of the human erythrocyte anion transporter (band 3) and their application to the analysis of South East Asian ovalocytes

This report describes the production and characterization of 13 rodent monoclonal antibodies to the human erythrocyte anion transport protein AE1 (syn. band 3). Eleven antibodies (4 murine and 7 rat) recognize epitopes dependent on the integrity of the third extracellular loop of the protein. Two antibodies (1 murine and 1 rat) recognize epitopes on the N-terminal cytoplasmic domain. Quantitative binding studies using radioiodinated IgG and Fab fragments of antibodies to extracellular epitopes on AE1 ranged from 77,000 to 313,000 (IgG) and from 241,000 to 772,000 (Fab) molecules bound at saturation. The results indicate that the epitopes recognized by different antibodies vary in their accessibility and suggest that there is heterogeneity in the organization of individual AE1 molecules in the red blood cell membrane. Quantitative binding studies on South East Asian ovalocytes using several antibodies to AE1 and an anti-Wrb show a marked reduction in the number of antibody molecules bound at saturation. These results are consistent with the existence of highly cooperative interactions between transmembrane domains of AE1 in normal erythrocytes and the disruption of these interactions in the variant AE1 found in South East Asian ovalocytes.     

Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans

Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin-induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra.     

Utilization of monoclonal antibodies in the treatment of leukemia and lymphoma

The generation of murine monoclonal antibodies reactive with human leukemia and lymphoma cells has recently led to clinical trials that have begun to evaluate the use of these reagents in the treatment of various leukemias and lymphomas. Several of these studies have demonstrated that infusion of monoclonal antibody can cause the rapid and specific clearance of leukemic cells from the peripheral blood. Intravenously administered antibody also rapidly binds to bone marrow lymphoblasts, and in one instance, has resulted in the partial regression of tumor cell infiltrates in lymph nodes and skin. Unfortunately, clinically significant responses have not in general been achieved, but these clinical studies have identified specific factors that result in the development of resistance to antibody- mediated lysis in vivo. These factors include the presence of circulating antigen, antigenic modulation, reactivity of monoclonal antibody with normal cells, immune response to murine antibody, and the inefficiency of natural immune effector mechanisms. Current research is now being directed towards developing methods to circumvent each of these obstacles. Future clinical studies utilizing antibodies in vitro or with different specificity may demonstrate greater therapeutic efficacy. In addition, monoclonal antibodies can be used as carriers of other cytotoxic agents and in conjunction with other agents that will reduce the total load. Monoclonal antibodies represent new and powerful reagents that may in the near future become an additional therapeutic modality for patients with malignant disease.     

某妇幼保健机构工作人员职业暴露监测

目的了解某妇幼保健院工作人员职业暴露情况,探讨职业暴露相关危险因素及预防对策。方法对该院2012年1-12月间55名工作人员发生职业暴露的监测数据进行统计分析。结果共发生工作职业暴露55例、57例次。其中暴露源不明确31例次（54.39％）,暴露源情况明确26例次（45.61％）。 57例次职业暴露人员中,保洁员和护士占82.46%（47例次）,其职业暴露发生率分别为9.76%和5.32%。职业暴露发生率居前3位的科室是门急诊、产科和保洁部,分别为29.51%、9.80%和9.76%;暴露人员的工龄≤3年者占87.72%（50例次）。暴露种类以锐器伤为主,占94.74%（54例次）,暴露物以头皮钢针为主（42.11％）,其次为注射器针头（19.30％）。 职业暴露主要环节为拔针（29.83％）,其次为医疗废物处置（28.07％）。结论保洁员、护士和低年资工作人员是职业暴露高危群体,应采取相关的防范措施,加强对其职业防护教育培训;加强对重点部门、环节的管理,降低医院工作人员职业暴露危害。     

老年前列腺癌患者中预测活检阳性率的相关参数分析研究

目的:为了评估老年前列腺癌患者中相关的参数包括年龄、家族史、前列腺体积、前列腺特异性抗原(PSA)、游离前列腺抗原(FPSA)、游离前列腺抗原(FPSA)/总前列腺抗原(TPSA)、PET-CT或者ECT检查阳性率在预测前列腺穿刺活检率的价值.方法:患者资料是从2008年7月～2013年10月期间我院被初步诊断为老年前列腺癌患者162例,在前列腺活检前行PET-CT或者ECT检查.逻辑回归分析来评估各参数的相关的风险性.建立回归方程式通过逐步回归的各项参数来评估阳性活检的结果,通过ROC分析使用接收区域的方式来评估预测价值.PET-CT或者ECT检查检测的肿瘤发生的准确率和活检结果的比较用卡方检验.结果:在这些患者中通过活检检测出前列腺癌的有60例患者(36.9％).U分析显示各项相关参数在患者诊断中均是影响因素,其中AUC值为0.8657.PET-CT或者ECT检查结果提示有前列腺癌或者有骨转移提示的患者为120例.统计结果提示影像学表现与活检结果之间并没有相关性,肿瘤的影像学表现并不是显著的预测因素.预测活检结果最为准确的参数是FPSA/TPSA(P=0.002).结论:各项参数在老年前列腺癌患者诊断中均是影响因素,合并各项参数的因素要比依靠单一参数而言可以明显提高预测活检率的准确性.确诊老年前列腺癌诊断上单纯通过PET-CT或者ECT检查上是有疑问的,影像学技术提供的诊断结果与PSA化验和活检结果比较更没有意义.     

A randomized phase II study of autologous cytokine-induced killer cells in treatment of hepatocelluar carcinoma

Purpose

This prospective study aims to explore the benefit of cytokine-induced killer cell (CIK) treatment in hepatocellular carcinoma patients, which has not yet been thoroughly studied before.

Methods

From January 2004 to May 2009, 132 patients who were initially diagnosed with hepatocellular carcinoma of Barcelona Clinic Liver Cancer (BCLC) stage A, B or C, Child–Pugh scores of A or B and without prior treatment were enrolled in the study. Patients were randomly assigned to either arm 1 (n?=?66) to receive CIK treatment plus standard treatment, or arm 2 (n?=?66) to receive standard treatment only. The primary end point was overall survival (OS) and the secondary endpoint was progression-free survival as evaluated by Kaplan–Meier analyses and treatment hazard ratios with the Cox proportional hazards model.

Results

The 1-year (OS: 74.2 % vs. 50.0 %, 95 % CI: 63.6–84.8 % vs. 37.8–62.2, p?=?0.002), 2-year (OS: 53.0 % vs. 30.3 %, 95 % CI: 40.8–65.2 % vs. 19.1–41.5 %, p?=?0.002), 3-year (OS: 42.4 % vs. 24.2 %, 95 % CI: 30.4–54.4 % vs. 13.8–34.6 %, p?=?0.005) and median overall and progression-free survivals of arm 1 patients were significantly higher than those of arm 2. Therefore, in patients who are not suitable for surgery, significant benefit is obtained from CIK treatment. The main adverse effects of CIK included fever, allergy and headache pain.

Conclusions

Hepatocellular carcinoma patients who were not suitable for surgery demonstrate prolonged overall and progression-free survival from CIK treatment.     

慢性磷中毒患者血清酶学检测结果分析

了解慢性磷中毒患者血清酶学的含量变化,探讨其在慢性磷中毒发病中的作用。应用全自动生化分析仪对慢性磷中毒患者血清中γ-谷氨酰转移酶(γ-GT)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、N-乙酰-β-D氨基葡萄糖苷酶(NAG)、乳酸脱氢酶(LDH)、肌酸激酶同工酶B(CK-MB)、亮氨酸氨基肽酶(LAP)、α1-抗胰蛋白酶(α1-AT)和前白蛋白(PA)进行测定和分析。结果显示,慢性磷中毒组与对照组比较,除PA明显下降外(P<0.01),其他各指标均明显升高(P<0.01)。分层分析,重度组与对照组比较,差异有显著性(P<0.01)。提示,慢性磷中毒患者的血清酶测定,可以了解磷对肝脏的损伤程度和范围,对慢性磷中毒的防治具有重要指导作用。     

北京市属医院知名专家团队双向转诊机制探讨

目前我国医联体建设已取得一定成效,但在实践过程中,仍存在医联体内上下转诊不畅的协同困境.北京市医院管理中心在市属医院内部进行分级诊疗制度创新,通过建立知名专家团队层级转诊预约模式,有效解决了疑难病"看专家难"问题.作者通过总结北京市属医院知名专家团队建设经验,探讨了院内知名专家团队层级转诊模式对医联体建设的借鉴意义.