体外免疫法抗MG7人源性单抗的研制及其意义

本文建立了人淋巴细胞体外致敏技术,用本文作者既往制备的鼠抗人胃癌单抗MG7作为免疫原,在体外致敏人淋巴细胞获得成功。经与本文作者在建立的人鼠种间骨髓瘤细胞系FMC-1进行人鼠人双杂交,获得一株能与鼠源性抗体反应,但不与人、羊、马、兔等其他种属动物产生的抗体相反应的人源性单抗HMG7。本文讨论了HMG7可能的应用价值,以及在人淋巴细胞体外致敏过程中应注意的几个环节。     

White matter damage precedes that in gray matter despite similar magnetic resonance imaging changes following cerebral hypoxia-ischemia in neonatal rats

We hypothesized that the cerebral injury produced by hypoxia-ischemia (HI) in neonatal rats would differ in white compared with gray matter as detected histologically or with magnetic resonance (MR) imaging methods. Maps of T₂ and the apparent diffusion coefficient (ADC) of water were acquired in 1-week-old rats at times prior to cerebral HI (right carotid artery occlusion plus 1.5 h of hypoxia), within the last 5–10 min of HI, and 1 h or 24 h after HI. Near the end of HI, ADC decreased and T₂ increased in both cortical gray and subcortical white matter within the cingulum of the HI hemisphere. One hour after HI, ADC partially recovered, but T₂ remained increased and then increased further by 24 h post-HI. In contrast to the similar MR responses in white and gray matter, histological evidence for irreversible cell damage occurred in white matter earlier than in gray matter within the HI hemisphere. At 1 h post-HI, rarefied or disrupted nerve fibers and an increase in TUNEL-positive cells were observed within white matter in the cingulum, whereas neurons within the cortical gray matter appeared normal. By 24 h post-HI, damage was apparent in both white and gray matter. Thus, MR imaging detected acute tissue edema following cerebral HI in both gray and white matter but did not distinguish between the early irreversible tissue injury detected histologically in white but not gray matter in this rather severe model of neonatal encephalopathy.     

Screening of human anti-TNF-alpha scFv from large phage library

AIM: To clone human anti-TNF-alpha scFv from large phage antibody library. METHODS: Panning of large phage library against TNF-alpha was conducted to select specific antibodies. The antigen binding activity and DNA sequence were determined and analyzed by ELISA, restriction enzyme map. RESULTS: After 4 rounds of panning, 62 positive clones were obtained and 27 clones had specific binding ability to TNF-alpha. DNA fingerprinting of the 27 clones showed 7 different stripes indicated 7 different positive clones. 5 of the 7 clones expressed soluble anti-TNF-alpha activity. DNA sequence analysis showed that the variable regions of these scFvs belonged to different subgroups. CONCLUSION: Human TNF-alpha scFv have been successfully obtained from large phage antibody library.     

纤维蛋白原Bβ链基因-1420G/A、-993C/T和-854G/A多态性与冠状动脉粥样硬化性心脏病的关联研究

目的调查健康人和冠状动脉粥样硬化性心脏病(简称冠心病)患者的纤维蛋白原B(fibrino-genB,FGB)β基因-1420G/A、-993C/T和-854G/A的基因多态性频率分布,以及与血浆Fg水平的关系。方法应用等位基因特异性PCR扩增技术和限制性片段长度多态性技术对186例冠心病患者和149名健康对照者进行分析。比浊法测定血浆Fg浓度。结果等位基因频率-1420A在冠心病组为0.33,在对照组为0.26,冠心病组明显比对照组升高,两者比较差异有统计学意义(P<0.05)。等位基因频率-993T和-854A在两组之间无差别。Logistic回归分析显示β-1420G/A与冠心病相关(OR=1.922,P=0.003)。冠心病组血浆Fg水平(3.87±1.75)g/L较健康人组(3.10±0.77)g/L明显升高,且差异有统计学意义(P<0·05)。结论纤维蛋白原Bβ-1420G/A可能与冠心病发病相关联。     

The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization

Choroidal neovascularization (CNV) is directly related to visual loss in some eye diseases, such as age-related macular degeneration. Although several human histological studies have suggested the participation of macrophages in CNV formation, the precise mechanisms are still not fully understood. In this study, we elucidated the role of ocular-infiltrating macrophages in experimental CNV using CCR2 knockout (KO) mice, wild-type mice, and C57BL/6 (B6) mice. CCR2 is the receptor of monocyte chemoattractant protein-1, and the number of infiltrating macrophage and the area of CNV were significantly reduced in CCR2 KO mice. Enriched ocular-infiltrating macrophages from B6 mice actually showed angiogenic ability in a dorsal air sac assay. Moreover, their expression of class II, CD40, B7-1 and B7-2 molecules, and the mRNA for potential angiogenic factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor alpha, was also observed. Collectively, we conclude that ocular-infiltrating macrophages play an important role in CNV generation.     

老年人脑白质疏松症血液流变性及血液成分的改变

对３８例老年脑白质疏松症（ＬＡ）患者进行了部分血液流变性和血液成分指标的测定。结果：与健康者比较，ＬＡ患者全血粘度、血浆粘度、ＲＢＣ刚性指数和聚集指数、纤维蛋白原显著增高，ＲＢＣ变形能力明显降低，血Ｈｂ、ＭＣＶ、ＭＣＨ、ＭＣＨＣ、ＲＤＷ－ＣＶ显著增高。提示：血液流变性异常和红细胞老化参与了ＬＡ的发生。设法纠正患者高粘和高凝状态、提高红细胞变形能力有益于阻止该病的进展     

单侧外周伤害性刺激诱发大鼠脊髓中转录因子CREB的双侧磷酸化(英文)

c AMP反应成分结合蛋白 (c AMP response elem ent-binding protein,CREB)是一种转录因子 ,它在磷酸化之后可调节靶基因的转录。 CREB在 13 3位置的丝氨酸的磷酸化 ,与脊髓中伤害性传入的处理有关 ,本文作者等用特殊抗体对此进行了免疫细胞化学研究。在正常大鼠 ,虽然几乎所有脊髓神经元的核中都可见 CREB的轻度着色 ,但磷酸化的 CREB仅见于双侧腰段脊髓的 ～ 层 (75± 15 vs60± 18)和 层 (9± 3 )。用福尔马林注射引起一侧后脚掌出现炎症时 ,可在双侧腰段脊髓看到磷酸化CREB细胞核的快速 (小于 5 min)和节段性的显著增多 ;它们主要分布在双侧背角表层 ～ 层 (2 5 4± 2 0 vs 2 62± 2 3 )、 层(115± 13 )和双侧 ～ 层 (3 46± 2 0 vs3 2 8± 2 6) ;而在对照和炎症组大鼠的胸段脊髓中均未见磷酸化 CREB的增加。在注射CFA诱发一侧炎症或切断一侧坐骨神经的实验组大鼠 ,也可看到至少延续到第三天的强而双侧性的 CREB的磷酸化。这种由一侧后肢伤害性传入引致腰段脊髓中镜像式双侧 CREB磷酸化的出现 ,与一般看到的损伤传入只在同侧脊髓背角引起某些神经化学改变的结果不同 ,可能是人神经损伤后或在实验动物中出现对侧镜像式疼痛过敏现象的基础     

6024例分娩的方式选择与新生儿结局

目的探讨阴道分娩和剖宫产对新生儿的风险。方法对6024例妊娠的分娩方式、剖宫产指征以及新生儿结局回顾性分析。结果剖宫产率为35.3%,其指征主要是头盆不称、社会因素、宫内窘迫、臀位等。分娩新生儿6016例,其中因各种疾患转儿科822例,占13.5%。主要转科原因为早产儿低体重、窒息、高胆红素血症和吸入综合症,各疾病发病率与分娩方式无关。结论剖宫产没有增加新生儿的风险,仍是解决难产的重要手段,但应严格控制手术指征。     

Intracellular factors, but not virus receptor levels, influence the age-related outcome of DHBV infection of ducks.

Previous serological studies of experimental infection with duck hepatitis B virus (DHBV) have shown that the outcome of infection depends largely on the age of the duck at the time of inoculation. To examine the hypothesis that decreased susceptibility with increased age might be due to the loss of the virus receptor on hepatocyte membranes in adult ducks, we performed receptor binding studies using intact serum-derived DHBV virions and purified liver plasma membranes from both young ducklings and adult ducks. These studies showed that (1) DHBV was able to bind specifically to duck liver plasma membranes but not to internal membranes; (2) this binding could be inhibited by a monoclonal antibody to DHBV preS, a corresponding region in hepatitis B virus that binds to human hepatocytes; and (3) there was no significant difference in the receptor binding ability between plasma membranes from ducklings and from adult ducks. Since hepatocytes in the neonatal ducks are actively dividing, in contrast to the situation in adult ducks, we examined the effect of partial hepatectomy on DHBV-carrier ducks. A sharp increase was noted in the level of DHBV in the serum after partial hepatectomy suggesting that DHBV replication was enhanced in dividing hepatocytes. Thus the age-related difference in susceptibility of ducks to DHBV infection is not due to loss of the receptor but may be related to an intracellular event associated with cell division.     

重组促红细胞生成素对血透患者NO的影响研究

目的 :探讨基因重组促红细胞生成素 (rHuEpo)对维持性血透患者血管活性介质一氧化氮 (NO)的影响。方法 :将长期规律性血透尿毒症患者 80例分为血液透析应用rHuEpo者 (HDepo组n =4 3例 ) ,血液透析不应用rHuEpo者 (HD组n =37例 ) ,根据血压情况两组再分为HDepo高血压亚组 (HDepo - 1组 ,n =2 3)、HDe po血压正常亚组 (HDepo - 2组 ,n =2 0 )和HD高血压亚组 (HD - 1组 ,n =19)、HD血压正常亚组 (HD - 2组 ,n =18)。另选尿毒症未透析患者 2 0例 (NHD组 )、原发性高血压患者 2 0例、健康对照组 35例 (CON组 )。HDepo组患者均接受rHuEpo治疗 3个月以上 ,用比色法测定血NO水平。结果 :尿毒症未透析患者血清NO水平明显高于正常对照组 ,p <0 0 0 1;尿毒症透析患者血清NO浓度较正常对照组高 ,p <0 0 0 1,但经透析治疗的尿毒症患者与尿毒症未透析者比较 ,血清NO水平较未透析者低 ,p <0 0 5 ;HDepo组经rHuEpo治疗三月后血NO浓度下降 ,与用药前及对照组比较 ,p<0 0 0 1,p <0 0 5。且用rHuEpo治疗后 ,HDepo组收缩压、舒张压、平均动脉压均较HD组高 ,p <0 0 0 1,血压增高与NO浓度的降低有相关性。结论 :rHuEpo可使尿毒症透析患者血NO浓度降低 ,rHuEpo致高血压与血NO浓度降低有一定的关系