抗人喉癌/抗VEGF双功能抗体制备及应用研究

目的：研制抗人喉癌／抗血管内皮因子（VEGF）双功能克隆抗体，用于喉癌抗血管生成治疗。方法：采用二次杂交瘤技术制备抗人喉癌／抗VEGF双功能抗体。经酶联免疫吸附试验法和SP法检测喉癌及癌前病患者血清及癌组织中VEGF的含量表达。结果：获得6株分泌抗人喉癌／抗VEGF双功能抗体的杂交瘤，经免疫组化证实与喉癌细胞特异性结合率为93％，而与血管内皮细胞结合率为89％。血清中VEGF含量表达，喉癌组与癌前病组及正常对照组相比差异均显著。IgG亚型鉴定为IgG2aBSAb抗体效价为1：25 600倍（ELISA法）。结论：二次杂交瘤法制备的双功能抗体具有均匀性、可控性、效价高、稳定性好，可用于喉癌抗血管生成治疗，动态检测可作为判断喉癌预后的客观指标。     

慢性肾盂肾炎发病与巨细胞病毒感染关系初探

应用免疫酶斑点法检测慢性肾盂肾炎病人尿液中巨细胞颊毒，同时应用ＥＬＩＳＡ法检测血中ＨＣＭＶ抗体，检测结果表明，尿中ＨＣＭＶ阳性率为５２．９％，血清中ＨＣＭＶ抗体为７５．９％，与正常对照组相比，并差非常显著，证明慢性肾盂炎发病与ＨＣＭＶ感染有关。     

光化学诱导的血栓形成性脑缺血及其代谢改变

本文用光化学法激发大鼠局部脑血栓形成，以组织病理学、局部脑血流量、皮层水含量、三磷酸腺苷、二磷酸腺苷，一磷酸腺苷、能量负荷、肌酸及乳酸为指标，探讨局部脑血栓形成后５天ｒＣＢＦ明显增高的可能机理。结果表明，血栓形成后局部脑组织ＡＴＰ水平进行性减少（Ｐ＜０．０１）、ＡＤＰ／ＡＴＰ及ＡＭＰ／ＡＴＰ比值明显升高（Ｐ均＜０．０１），ＬＡ及脑水含量显著增加（Ｐ＜０．０１）。这些因素既是能量衰竭、无氧酵解的结果     

白三烯C_4对大鼠胃粘膜微循环的影响及其在急性胃粘膜损伤中的作用

探讨了静注白三烯C_4(0.1ng·100g~(-1))对胃粘膜微循环的影响及其在急性胃粘膜损伤中的作用。实验由Wistar系雄性大鼠,实验前禁食24hr,饮水不限。发现:1.胃粘膜表层毛细血管口径迅速变细,部分消失,集合细静脉口径亦变细;10分钟时集合细静脉明显淤血和出血。2.氢气清除法证明,胃粘膜血流量明显减少,注后第15分钟时由注前1.230±0.093(M±SE)降至0.521±0.079ml·min~(-1)·100g~(-1)(P<0.01)。3.反射光谱法证明,胃粘膜局部表层微循环血液量(△Er)和Hb氧饱和度(F),均有不同程度下降。4.静注白三烯C_4(0.1ng·100g~(-1))及盐酸灌胃(0.2N1ml)均未见明显胃粘膜损伤,两者并用则损伤明显加重。结果表明,外源性白三烯C_4可引起严重胃粘膜微循环障碍,是诱发溃疡形成的重要因素之一。     

The effect of alphaMSH analogues on rat bones

Melanocortin is the downstream mediator of leptin signaling and absence of leptin signaling in ob/ob and db/db mice revealed the enhancement of bone formation through the central regulation. While alpha-melanocyte-stimulating hormone (alphaMSH) inhibits the secretion of interleukin-1alpha and tumor necrosis factor-alpha from the inflammatory cells, alphaMSH can also enhance clonal expansion of pro B cells linked to stimulation of osteoclastogenesis. Therefore, we tested the effect of melanocortin on bones. alphaMSH analogues [(6)His]alphaMSH-ND and [(6)Asn]alphaMSH-ND were synthesized and the radio-ligand receptor binding- and cyclic AMP generating activity were analyzed in China Hamster Ovary cell line over- expressing melanocortin receptors. The EC(50) of [(6)His]alphaMSH-ND measured from melanocortin-1, 3, 4 and 5 receptors were 0.008 +/- 0.0045, 1.523 +/- 0.707, 0.780 +/- 0.405, and 250.320 +/- 42.234 nM, respectively, and the EC(50) of [(6)Asn]alphaMSH-ND were 16.8 +/- 6.94, 271.8 +/- 21.95, 8.0 +/- 1.21, and 1132.5 +/- 635.46 nM, respectively. Four weeks after the subcutaneous injection of the analogues, the body weights in the [(6)His]alphaMSH-ND and the [(6)Asn]alphaMSH-ND treated groups (346.0 +/- 20.63 g vs. 350.0 +/- 13.57 g) were lower than that of the vehicle treated group (375.8 +/- 17.31 g, p < 0.05). There was no difference in the total femoral BMD measured by dual x-ray absorptiometry among the three groups. Among the three groups, there were no differences in the total numbers of crystal violet positive- or alkaline phosphatase positive colonies, in the expression of Receptor Activator of Nuclear Factor Kappa-B ligand on the tibia and the total number of multinucleated osteoclast-like cells differentiated from primary cultured bone marrow cells. From the above results, no evidence of bone gain or loss was found after treatment of the alphaMSH analogues peripherally.     

乙醇对人绒毛孕酮分泌的影响

本工作利用灌流技术观察了四种不同浓度的乙醇(0.5％、1％、2.5％、5％)对妊娠早期人工流产新鲜胎盘绒毛分泌孕酮的影响。结果表明,乙醇具有促进孕酮分泌的作用,并存在剂量依赖的关系。提示乙醇可能破坏胎盘激素内分泌的平衡,从而影响胎儿的正常生长与发育。     

Immunogenicity of recombinant Plasmodium falciparum SERA proteins in rodents

We have expressed defined regions of the serine-repeat antigen (SERA) of the Honduras-1 strain of Plasmodium falciparum in the yeast Saccharomyces cerevisiae. Amino-terminal domains of the natural SERA protein have been shown previously to be targets for parasite-inhibitory murine monoclonal antibodies. Two recombinant SERA antigens were selected for purification and immunological analysis. The first (SERA 1), corresponding to amino acids 24-285 of the natural SERA precursor, was expressed by the ubiquitin fusion method. This allowed for in vivo cleavage by endogenous yeast ubiquitin hydrolase, and subsequent isolation of the mature polypeptide. The second, larger protein (SERA N), encompassing amino acids 24-506, was expressed at only low levels using this system, but could be isolated in high yields when fused to human gamma-interferon (gamma-IFN). Each purified protein was used to immunize mice with either Freund's adjuvant or a muramyl tripeptide adjuvant that has been used in humans. Sera from immunized mice were shown to be capable of in vitro inhibition of invasion of erythrocytes by the Honduras-1 strain of P. falciparum. The results suggest that a recombinant SERA antigen may be an effective component of a candidate malaria vaccine.     

大鼠心冠状动脉系统神经肽Y年龄变化的免疫组织化学研究

运用免疫组化ＡＢＣ法对不同月龄ＳＤ大鼠心脏冠状动脉及其分支含神经肽Ｙ神经纤维的分布及其衰老变化作了详细观察．结果表明：左、右冠状动脉及其各级分支具有丰富的神经肽Ｙ能神经分布．在冠状动脉主干及其较大分支上，神经纤维较稠密，主要呈环状或网状分布，在血管围周形成较多束、丛、网，并伸入血管壁内形成壁内的神经网络分布．部分神经纤维的游离末梢有穿过血管内膜伸向腔面的迹象．在细小的冠状动脉分支上，神经纤维密度减低，主要沿血管长袖是纵向分布．两侧冠状动脉系统神经肽Ｙ能纤维分布形式及密度没有差别．老龄组动物，左、右冠状动脉及其分支的神经肽Ｙ能纤维密度趋于下降，纤维变细，呈断续状，膨体数量减少，免疫染色变浅、此外，在心内发现了神经肽Ｙ能神经节．     

猕猴输精管内注射高分子聚合物HFMC后对睾丸组织结构的影响

本实验选用具有生育力成年雄性猕猴７只，在直视下行双侧ＨＦＭＣ输精管内注射，每侧剂量分别为３０ｍｇ１只，６０ｍｇ和１００ｍｇ各３只；于注射后２．５年和３．５年分别处死动物，取睾丸组织进行光镜和电镜观察．结果发现：猕猴注射ＨＦＭＣ２．５年后，睾丸光镜大部分曲细精管生精上皮结构完整，排列整齐。仅见局部少数管腔生精上皮层数减少，上皮细胞轻度水样变性等病理改变。电镜下曲细精管内除支持细胞内脂褐素增多，轻度基底膜增厚和精母细胞内质网扩张外，各级生精细胞，支持细胞及细胞间连接复合体等超微结构未见明显异常。注射ＨＦＭＣ３．５年后猕猴的光镜、电镜结果与注射后２．５年结果相似，但局部改变较２．５年组轻。上述结果表明：猕猴输精管内注射一定剂量ＨＦＭＣ节育不会引起睾丸组织的严重病理改变。但是，由于注射ＨＦＭＣ后，ＨＦＭＣ释放Ｈ＋及其对输精管的暂时阻塞，改变了精子生存的内环境，使睾丸出现局部轻度病理改变，随着ＨＦＭＣ逐渐溶解排出，睾丸功能相继恢复正常，配对产仔。为ＨＦＭＣ应用提供了安全性依据。     

Mitotic activity of lymphocytes in the thymus cortex during hypokinesia and readaptation

Changes in the weight and mitotic index in the thymus cortex of Wistar rats were studied during hypokinesia for 10 days followed by recovery for the same period. The mitotic index was reduced by half, 24 h after immobilization of the animals. During readaptation a stage of secondary stress (when the mitotic index was reduced by 71%) was followed by a stage of true readaptation after 10 days.Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. Institute of Marine Biology, Vladivostok. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 10, pp. 480–482, October, 1979.