Elimination of myeloma cells from bone marrow by using monoclonal antibodies and magnetic immunobeads

The efficacy of immunomagnetic beads to purge human myeloma cells from bone marrow ex vivo was evaluated. The optimal conditions for purging were studied first by using three myeloma cell lines: RPMI-8226, SKO- 007, and SKMM-2. Myeloma cells labeled with the vital fluorescent dye Hoechst 33342 were admixed with normal bone marrow cells, and two monoclonal antibodies reactive with the myeloma cells (PCA-1 and BL-3) were added alone or in combination with the cells. Magnetic beads coated with goat antimouse immunoglobulin G were then added, and the tumor cells to which beads were attached were separated from the mixture with a magnet. The efficacy of tumor cell removal was dependent on the bead-to-tumor ratio; a ratio of more than 500 was optimal in the presence of excess normal marrow cells. The combination of monoclonal antibodies PCA-1 and BL-3 increased the tumor cell removal as compared with either antibody alone. Two cycles of treatment were more effective than one cycle was. Under optimal conditions, 2.3 to 4 logs of tumor cells could be removed from the mixture containing 10% myeloma cells without a significant loss of normal hematopoietic progenitors as measured by CFU-GM, CFU-GEM, and BFU-E. When the efficacy of this procedure was tested on fresh bone marrow from patients with multiple myeloma (MM) by using the combination of PCA-1, BL-3, and J-5, 1.6 to 2.5 logs of tumor cells could be removed by one cycle of treatment, even from marrows containing less than 10% myeloma cells. These observations support the use of monoclonal antibody combinations and immunobeads as a reliable and nontoxic method to eliminate contaminating myeloma cells ex vivo in preparation for autologous bone marrow transplantation in patients with MM.     

血管紧张素原基因5’端启动子区A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压的相关性

目的:分析血管紧张素原基因启动子区A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压的相关性。方法:实验于2005-08/2006-01在北京华大实验室完成。选取对象均为生活在内蒙古乌拉特后旗的蒙古族牧民,三代血亲内无其他民族。采用基因测序技术对内蒙古蒙古族人群中107例原发性高血压患者和108例正常对照者进行A-20C和A-6G基因分型,观察高血压组和正常对照组不同基因型的分布和等位基因频率的差异。结果:①两组受试者在性别、年龄及吸烟、饮酒、体质量指数和临床化验检查指标有较好的匹配(P均>0.05)。②两组血管紧张素原基因A-20C位点AA,AC,CC基因型频率比较差异无显著性意义(高血压组分别为0.51,0.29,0.20;正常对照组分别为0.49,0.28,0.23,χ2=0.395,P=0.529)。A,C等位基因频率比较差异无显著性意义(高血压组分别为0.65,0.35;正常对照组分别为0.63,0.37,χ2=0.015,P=0.904)。③两组血管紧张素原基因A-6G位点AA,AG,GG基因型频率比较差异无显著性意义(高血压组分别为0.50,0.33,0.17;正常对照组分别为0.55,0.34,0.11,χ2=1.924,P=0.165)。A,G等位基因频率比较差异无显著性意义(高血压组分别为0.66,0.34;正常对照组分别为0.72,0.28,χ2=1.728,P=0.189)。④高血压组协同存在血管紧张素原基因A-20C基因型CC时,血管紧张素原基因A-6G基因型GG频率稍高于正常对照组,但差异无显著性意义(χ2=2.395,P=0.122,OR=7.52,95%CI0.014～1.250),高血压组G等位基因明显高于正常对照组(分别为0.37,0.22,χ2=4.658,P=0.034),携带该等位基因的蒙古族人群发生原发性高血压的相对危险度升高(OR=2.80,95%CI1.087～7.271)。结论:血管紧张素原基因A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压相关,并可能具有协同作用。     

藏族糖尿病患者代谢功能改善与面对面教育的效应

目的:观察面对面随访方式的糖尿病教育对藏族患者代谢功能改善的作用。方法:①选择2005-08/2006-08在西藏军区总医院心内科住院和门诊就诊的糖尿病患者113例。男69例,女44例;年龄48～71岁。纳入糖尿病患者均符合1999年世界卫生组织糖尿病诊断标准,且对检测项目知情同意;均为离解放军西藏军区总医院最近的娘热乡藏族糖尿病患者。②测量身高、体质量、收缩压、舒张压,计算体质量指数=体质量/身高2。采用日立7600型全自动生化分析仪测定血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇水平。采用TosohHLC-723GHbV型高压液相色谱仪测定糖化血红蛋白。③所有参试者得到一份本院编写的藏汉对照糖尿病教育手册,并在分组前统一讲解,以上大课的形式进行普及教育。根据每个患者不同情况,由内分泌专业医师给予不同处方,包括饮食、用药、生活方式调整。随后将患者随机分为教育组56例(男35例,女21例)和对照组57例(男34例,女23例)。对照组主要采用患者主动咨询(电话咨询或医院复查)和每一两个月一次普及教育的方式,但医生不采用面对面主动干预;教育组的干预方式除上述普及教育以外,每2周进行一次面对面、一对一随访,并及时调整处方。半年后比较两组的代谢指标差异。④计量和计数资料的差异比较分别采用方差分析和χ2检验。结果:藏族糖尿病患者113例均完成随访并进入结果分析。①组间比较:干预前两组体质量指数、收缩压、舒张压、总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、糖基化血红蛋白比较,差异不明显(P>0.05)。教育半年后教育组的体质量指数、收缩压、舒张压、总胆固醇、三酰甘油、低密度脂蛋白胆固醇和糖化血红蛋白均明显低于对照组(t=2.0156～4.7592,P<0.05～0.01),高密度脂蛋白胆固醇明显高于对照组(t=3.8031,P<0.01),其中以糖基化血红蛋白差异最明显。②组内比较:教育组糖尿病教育半年后血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇和糖化血红蛋白均较干预前明显降低(t=1.9832～3.6446,P<0.05～0.01),高密度脂蛋白胆固醇较干预前升高(t=2.8219,P<0.01),教育干预前后体质量指数无明显变化(P>0.05)。对照组糖尿病教育半年后,体质量指数、总胆固醇、三酰甘油、低密度脂蛋白胆固醇和糖化血红蛋白、高密度脂蛋白胆固醇与教育前相近(P>0.05)。结论:藏族糖尿病患者采取面对面的随访方式进行糖尿病教育较一般形式的糖尿病教育更好的改善其代谢功能。     

Photographic protocol for image acquisition in craniofacial microsomia

Craniofacial microsomia (CFM) is a congenital condition associated with orbital, mandibular, ear, nerve, and soft tissue anomalies. We present a standardized, two-dimensional, digital photographic protocol designed to capture the common craniofacial features associated with CFM.     

Proton pump inhibitor and clopidogrel interaction: The case for watchful waiting

Clopidogrel is an integral part of the management of several important vascular diseases. However the medium to long term clinical outcomes are poorer for these patients if they experience gastro‐intestinal bleeding, hence patients with risk factors for gastro‐intestinal bleeding are frequently prescribed proton pump inhibitors. Conflicting evidence exists as to the existence of an adverse interaction between clopidogrel and proton pump. This review examines the original studies, which suggested the adverse interaction, the subsequent and most recent studies, the pharmaco‐dynamics of the two drugs and suggests an algorithm for the use of clopidogrel with proton pump inhibitors.     

MAGNOLOL REDUCES INFARCT SIZE AND SUPPRESSES VENTRICULAR ARRHYTHMIA IN RATS SUBJECTED TO CORONARY LIGATION

1. Magnolol is an active component of Magnolia officinalis. It is 1000-times more potent than α-tocopherol in inhibiting lipid peroxidation in rat heart mitochondira. In the present study, the in vivo antiarrhythmic and anti-ischaemic effects of magnolol in coronary ligated rats were investigated. 2. Male Sprague-Dawley rats were anaesthetized with urethane. Magnolol, at dosages of 10^?7, 10^?8 and 10^?9 g/kg, was adminstered intravenously 15 min before ligation of the coronary artery. 3. The incidence and duration of ventricular tachycardia and ventricular fibrillation during 30 min coronary ligation were significantly reduced by magnolol. Ventricular arrhythmias during 10 min reperfusion after the relief of coronary ligation were also reduced. 4. In rats subjected to 4h coronary ligation, 10^?7 and 10^?8 g/kg magnolol significantly reduced infarct size. 5. We conclude that magnolol may protect the myocardium against ischaemic injury and suppress ventricular arrhythmia during ischaemia and reperfusion.     

环孢素A和他克莫司对移植肾P-糖蛋白表达的影响：3年随访移植肾活检

目的:观察环孢素A和他克莫司对人类移植肾组织P-糖蛋白表达影响的差异,分析两种药物肾毒性差异的分子作用途径。方法:实验于2005-01/12在南京医科大学临床肾脏病学实验室完成。选择在南京医科大学第一附属医院泌尿外科肾移植中心接受肾移植的患者60例,肾移植后时间均在3年以上,根据移植后免疫抑制方案不同将其分为2组,环孢素A组32例患者采用强的松(5mg/d) 骁悉(1.5g/d) 环孢素A(初始剂量为5mg/(kg·d))免疫抑制治疗;他克莫司组28例患者采用强的松 骁悉 他克莫司(初始剂量为0.1mg/(kg·d))免疫抑制治疗,强的松、骁悉剂量同环孢素A组。①记录两组患者的一般临床资料。②移植肾活检,比较肾组织慢性移植肾排斥的班夫评分(Ⅰ级:间质浸润同时发现中度或重度动脉炎病灶;Ⅱ级:轻度或重度内膜炎或严重的动脉内膜炎并涉及>25%的腔体;Ⅲ级:跨壁动脉内膜炎和/或动脉纤维样变和内侧平滑肌细胞坏死伴随淋巴细胞炎症)及平均慢性化病变积分(由小管萎缩、动脉病变、间质纤维化3项评分得出的均值,其中每项0~3分,依次表示<25%,26%~50%,51%~75%和>75%的观察视野)。③免疫组织染色检测移植肾P-糖蛋白的表达并借助图像分析软件比较其在近端肾小管染色强度(半定量为0~4级,0为阴性,4为最强)的差异。结果:60例患者全部进入结果分析。①环孢素A组血肌酐、尿蛋白排泄量及血脂水平显著高于他克莫司组(P<0.05),肌酐清除率显著低于他克莫司组(P<0.05)。②肾毒性指标小管萎缩、动脉透明样变、间质纤维化的发病人数环孢素A组显著高于他克莫司组(P<0.05),环孢素A组慢性化病变积分也显著高于他克莫司组(P<0.05)。③P-糖蛋白主要分布于肾小管顶膜、基底膜和细胞浆内。环孢素A组的染色强度显著低于他克莫司组(3.1±0.7,3.8±0.4,P<0.01)。结论:应用环孢素A进行肾移植术后免疫抑制的患者发生神经钙调蛋白抑制剂肾毒性的比率和程度均明显高于他克莫司组,其中P-糖蛋白的表达水平低下是其可能的分子作用途径。     

应用Heath-Carter体型法分析辽西地区城市汉族儿童青少年1263名体型特征

目的:分析辽西地区城市汉族儿童青少年的体型发育规律和特点,为体质人类学补充必要的数据。方法:按整群分层抽样法,抽取2001-07/2003-09辽西地区城市7所中小学7～19岁经学校正常体质检查证明身体健康的汉族学生,按性别分两大组,每大组按年龄分12小组,7～18岁每岁为1个年龄组,18～19岁为1个年龄组,每小组45～86名,共分24组,搜集完整资料1263名(男657名,女606名)。采用Heath-Carter体型法,每项指标测量2次,取平均值,10项指标由专人负责,测试数据按年龄和性别在微机中建立数据库,依次计算出各年龄组的内因子、中因子和外因子,体型图上的X,Y坐标值,身高/体质量1/3,样本中平均体型点到所有体型点空间距离的均数,三维空间中两个体型点间的差异,体脂含量和各类体型分布频数。结果:参加调查1263名,均进入结果分析。①7～17岁儿童青少年身高、体质量随年龄的增加而增长。平均身高、体质量男生大于女生。身高/体质量1/3指数除14,16和17岁外,各年龄组女生>男生,平均值女生>男生。体脂含量11岁以前男生>女生,12岁以后女生>男生。②辽西地区城市汉族男生的平均体型值为3.9-3.5-3.4,属中间型,女生平均体型值为4.3-2.9-3.6,属偏外胚层的内胚层体型。体型频数的变化提示辽西城市汉族男生体型分布较散,女生分布较集中,主要在内胚层体型。③内因子男生在3.18～4.81,女生在3.05～5.33,11岁以前男生>女生,12岁以后女生>男生;中因子男生在3.02～4.23,女生在2.54～3.42,除16岁男女相差不多外,其他年龄组男生>女生,外因子男生在2.64～4.22,女生在2.92～4.14,13岁以前女生>男生,14岁以后男生>女生。因此,男生较女生骨骼粗壮,肌肉发达,随着年龄的增长,女生的皮下脂肪更发达,体态丰满,男生的身体相对瘦高程度增长,身材修长。男女各年龄组间体型比较,7～,8～,9～,10～,11～,12～,13～,14～,15～,16～,17～,18～19岁三维空间中两个体型点间的差异值分别为0.95,0.85,1.10,1.06,1.37,0.43,0.87,1.44,1.42,1.12,1.11,1.33,7～,8～,12～,14～,17～,18～19年龄组男女间体型差异有显著性(t=2.07,4.09,3.12,3.86,3.39,3.99,P<0.05)。④与国内汉族及其他少数民族相比,辽西汉族男生体脂最多,骨骼肌肉不发达,身体相对矮小;辽西地区汉族女生体脂较多,骨骼肌肉不发达,体型修长。结论:辽西地区城市男生较女生骨骼粗壮,肌肉发达,随着年龄的增长,女生的皮下脂肪更发达,体态丰满,男生的身体相对瘦高程度增长,身材修长。与国内汉族及其他少数民族相比,辽西地区城市汉族儿童青少年体脂发育较好,骨骼肌肉欠发达,青春期是形成健壮体型的关键时期,辽西地区城市儿童青少年应注意合理饮食和加强体育锻炼。