血脂调节剂的研究——Ⅰ.HMG-CoA还原酶抑制剂M-8614A及MH-2688B产生菌的筛选

利用酶联免疫吸附测定法,酶标β-羟基β-甲基-戊二酸单酰铺酶A(HMG-CoA)还原酶抑制剂Compactin抗体,定向筛选血脂调节剂。从青霉M-8614菌株发酵液中分离到M-8614A。该物质理化性质及波谱解释表明与Mevastatin为同一物质。 M-8614菌株用亚硝酸盐等诱变剂处理,从诱变株MH-2688发酵液中分离到MH-2688B。该物质理化性质及波谱解释表明与Lovastatin为同一物质。     

The Effect of Total Blood Exchange with PHP Solution on Cardiac Xenotransplantation

Abstract: Prevention of hyperacute rejection is a difficult and unsolved problem in xenotransplantation. Natural antibodies and complement activation have been known to play an important role in the xenotransplantation between discordant species pairs. In the present study, total blood exchange (TBE) was performed with pyridox-alated-hemoglobin-polyoxyethylene conjugate (PHP) solution (Ajinomoto Co., Inc., Kawasaki, Japan) before cardiac xenotransplantation in order to remove the immunoglobulins and prolong xenograft survival time. Guinea pigs and rats were used as the discordant species combination for donor and recipient. Two groups were established: Group 1, untreated control (n = 8) and Group 2, TBT with PHP solution (n = 8). The exchange blood transfusion was carried out at the rate of 15–20 ml/h utilizing PHP solution using a blood pump. After the blood exchange was processed, hematocrit (Ht) levels dropped to 4 or 5%, and a cardiac xenotransplantation was performed within 24 h. The levels of serum IgA, IgM, and IgG were decreased to less than 25, 25, and 10% of the base line, respectively, after blood exchange. A mean xenograft survival time in Group 2 was prolonged to 472 ± 74 min and to 10.4 ± 1.8 min in Group 1 (p < 0.01). A titer of the anti-guinea pig lymphocytotoxic antibody in rat serum was decreased to almost nil. The data from this study suggest that total blood exchange with PHP solution may be useful in preoperative removal of xenograft antibodies in xenotransplantation.     

Apolipoprotein E—associated risk for Alzheimer's disease in the African-American population is genotype dependent

As a part of our ongoing study on Alzheimer's disease (AD) in elderly African Americans, we obtained clinical assessment and apolipoprotein E (ApoE) genotype data on 288 individuals (including 60 with AD). The ApoE σ4 allele frequency was significantly increased in AD patients compared with controls. The age-adjusted odds ratio (OR) for AD in σ4 homozygotes was 4.83 (95% confidence interval [CI], 1.71–13.64) compared with the σ3/σ3 genotype, but the OR for AD with the σ3/σ4 genotype did not reach significance (1.20; 95% CI, 0.58–2.45). These findings suggest that the association between ApoE σ4 and AD is weaker in African Americans than in whites.     

慢性乙型肝炎伴肝胆结石病人胆汁、外周静脉血、门静脉血中HBsAg和HBV-DNA的存在探讨

对29例慢性乙型肝炎伴肝胆结石患者.采用Elisa和斑点杂交技术检测外周静脉血、胆管胆汁和门静脉血中乙型肝炎两对半及HBV-DNA.并比较HkAg含量.结果，外周静脉血、胆汁和门静脉血中HBsAg浓度分别为;2244.73±59722ng／ml、1181.65±370.91ng／ml、2013.62±483.47ng／ml;HBV-DNA阳性检出率分别为62.07％（18例），72.41％（21例）及68.97％（20例）.提示肝细胞内复制的HHV在进入血循环的同时，部分随胆汁的分泌排入肠道，并可能通过受损肠粘膜进入门静脉再回到肝脏，造成HBV对肝脏的重复感染。     

红霉素对犬幽门括约肌压力影响及其与胃动素,生长抑素的关系

为探讨红霉素对犬幽门括约肌的作用及其机理，及其与血浆胃动素，生长抑素的关系。方法采用胃压力测量仪及放射免疫法，同步监测观察了１０条犬静脉滴ＥＭ前后和使用拮抗剂后的幽门压力、血浆ＭＴＬ，ＳＳ的变化，结论：ＥＭ具有增高犬胃幽门压力的作用，其作用机理除与血浆ＭＴＬ有着密切的关系外，血浆ＳＳ也可能共同参与了其调节机制。     

薄荷醇对戊巴比妥中枢抑制作用的影响

研究薄荷醇经胃肠道给药对成巴比妥中枢抑制作用的影响，结果发现，薄荷醇对戊巴比妥的中枢抑制作用具有一定的量效关系，含４．５％的薄荷醇溶液可明显使小鼠的入睡时间缩恒，并使急性死亡率增加，而含１．５％和０．５％的薄荷醇溶液对成巴比妥的中枢抑制作用无明显影响。     

抑肽酶对长期低温保存兔肺的保护作用的研究

目的 :探讨抑肽酶对长期低温保存兔肺保护作用。方法 :应用离体兔肺缺血再灌注模型 ,15只白兔随机分为三组 (抑肽酶组、对照组 1、对照组 2 ) ,抑肽酶组和对照组 1用Euro -Collins液进行肺灌洗和低温保存(10℃ ,2 4h)后 ,以新鲜兔血离体灌注 30min。抑肽酶组在兔血中加入抑肽酶 (2 5万KIU) ;对照组 1不用抑肽酶。对照组 2取自正常兔肺 ,不进行肺灌洗和保存。灌注中测定肺动脉氧差 (△PO2 ) ,肺动脉压 (PAP) ,灌注完毕取肺电镜观察微观结构。应用TUNEL(末端脱氧核糖核酸转移酶 (TdT)介导的dUTP缺口末端标记 )技术检测肺细胞凋亡情况。结果 :与对照组 1比较 ,抑肽酶组的动静脉氧差较大 (2 0min时差异显著 ,P <0 .0 5 ) ,肺动脉压较低 (P <0 .0 5 )。电镜观察对照组 1肺结构破坏重。细胞凋亡检测显示对照组 1细胞凋亡数目高于抑肽酶组 (P =0 .0 0 18)和对照组 2 (P =0 .0 0 0 1) ,抑肽酶组细胞凋亡数目高于对照组 2 (P =0 .0 0 0 )。结论 :抑肽酶对于长期低温保存的兔肺有保护作用。细胞凋亡可作为评价肺移植后保护效果的指标之一。     

冠心病患者血脂异常与胰岛素抵抗的关系

目的 :探讨冠心病患者血脂异常与胰岛素抵抗的关系。方法 :观察 68例冠心病患者与 66例对照者的血脂、血糖、胰岛素等生化指标 ,以胰岛素释放指数———空腹胰岛素 (FIns) /空腹血糖 (FBG)和胰岛素敏感指数(1 /FBG×FIns)作为胰岛素抵抗 (IR)的指标 ,与空腹血脂进行直线相关分析。结果 :冠心病组与对照组对比 ,血糖水平无明显差异 (P >0 .0 5) ,而血胰岛素、胰岛素释放指数明显较对照组增高 (P <0 .0 5) ,胰岛素敏感指数明显较对照组低 (P <0 .0 5)。冠心病组的甘油三酯 (TG)、总胆固醇 (TC)、低密度脂蛋白胆固醇 (LDL -C)明显较对照组增高 (P <0 .0 5)、高密度脂蛋白胆固醇 (HDL -C)明显较对照组低 (P <0 .0 5)。冠心病组胰岛素释放指数、胰岛素敏感指数分别与TG ,TC和LDL -C呈正相关 ,与HDL -C呈负相关。结论 :冠心病患者存在着高胰岛素血症和胰岛素抵抗 ,而且冠心病患者的胰岛素抵抗和血脂异常密切相关。     

脐血CD34^＋细胞免疫表型的分析

应用免疫磁珠法分离脐血ＣＤ３４＾＋细胞，以比较ＣＤ３４＾＋细胞亚群及各系相关抗原的变化。经过分离，ＣＤ３４＾＋细胞由１．４７±０．７７％升至５７．３９±１６．１７％，分离后ＣＤ３４＾＋ＣＤ３８＾－细胞占ＣＤ３４＾＋细胞的比率为７．８２±４．７９％ＣＤ３４＾＋。细胞纯化同时可减少ＣＤ３＾＋细胞达１４．１２±９．１８倍，ＣＤ１５＾＋细胞减少１６．４２±２１．４７倍；Ｂ系（ＣＤ１９）、巨核系（ＣＤ４１）     

抗—HCV阳性单采浆供血员HGV感染随访研究

为了解单采浆供血员庚型肝炎病毒（ＨＧＶ）感染及其转归，对１０２名抗－ＨＣＶ阳性单采浆供血员冻存血清进行抗－ＨＧＶ和ＨＧＶＲＮＡ检测，对抗－ＨＧＶ和（或）ＨＧＶＲＮＡ阳性者作３年随访研究。采用ＥＩＡ法检测抗－ＨＧＶ，包被抗原来自ＨＧＶ不同功能区的合成肽。应用ＲＴ－ＰＣＲ法检测ＨＧＶＲＮＡ，引物选自ＨＧＶＮＳ３区。结果表明，抗－ＨＣＶ阳性单采浆供血员ＨＧＶＲＮＡ阳性率为１９．６１％（２０／１０２），抗－ＨＧＶ阳性率为１７．６５％（１８／１０２），ＨＧＶ感染率（抗ＨＧＶ和／或ＨＧＶＲＮＡ阳性）为２４．５１％（２５／１０２），而对照组仅为０．９４％（１／１０６）。提示单采血浆是ＨＧＶ感染的重要危险因素。ＨＧＶＲＮＡ和抗－ＨＧＶ的３年阴转率分别为３５．００％（７／２０）和１１．１１％（２／１８），说明ＨＧＶ感染有慢性携带趋势