The 2.0-Å resolution crystal structure of a trimeric antibody fragment with noncognate VH–VL domain pairs shows a rearrangement of VH CDR3

The 2.0-Å resolution x-ray crystal structure of a novel trimeric antibody fragment, a “triabody,” has been determined. The trimer is made up of polypeptides constructed in a manner identical to that previously described for some “diabodies”: a V_L domain directly fused to the C terminus of a V_H domain—i.e., without any linker sequence. The trimer has three Fv heads with the polypeptides arranged in a cyclic, head-to-tail fashion. For the particular structure reported here, the polypeptide was constructed with a V_H domain from one antibody fused to the V_L domain from an unrelated antibody giving rise to “combinatorial” Fvs upon formation of the trimer. The structure shows that the exchange of the V_L domain from antibody B1-8, a V_λ domain, with the V_L domain from antibody NQ11, a V_κ domain, leads to a dramatic conformational change in the V_H CDR3 loop of antibody B1-8. The magnitude of this change is similar to the largest of the conformational changes observed in antibody fragments in response to antigen binding. Combinatorial pairing of V_H and V_L domains constitutes a major component of antibody diversity. Conformationally flexible antigen-binding sites capable of adapting to the specific CDR3 loop context created upon V_H–V_L pairing may be employed by the immune system to maximize the structural diversity of the immune response.     

溴氰菊酯对白纹伊蚊（Aedesalbopictus）C6／36细胞株的细胞遗传学效应

本研究选择１０μｇ／ｍｌ、２０μｇ／ｍｌ、４０μｇ／ｍｌ浓度的溴氰菊酯处理白纹伊蚊Ｃ６／３６细胞，以ＭＭＣ作为阳性对照物，观察溴氰菊酯处理２４ｈ后对Ｃ６／３６细胞染色体畸变率和姐妹染色单体互换（ＳＣＥ）频率的影响。结果显示，三个浓度的溴氰菊酯对Ｃ６／３６细胞染色体畸变率均没有显著影响（Ｐ＜０．０５）；溴氰菊酯浓度在４０μｇ／ｍｌ时可诱导Ｃ６／３６细胞ＳＣＥ频率轻度增高（Ｐ＞０．０５），而溴氰菊酯浓度在１０μｇ／ｍｌ、２０μｇ／ｍｌ时，对Ｃ６／３６细胞ＳＣＥ频率没有诱导作用。表明溴氰菊酯对Ｃ６／３６细胞的遗传学效应较弱     

The effect of MS-818, a pyrimidine compound,on the regeneration of peripheral nerve fibers of mice after a crush injury

One of the pyrimidine compounds, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4-d]pyrimidine (MS-818), has neurotropic effects in vitro. Therefore, we studied the effect of MS-818 on the regeneration of the peroneal nerve in C57BL/6J mice after a crush injury. Two test groups, which received a daily intraperitoneal injection of 5 mg/kg or 10 mg/kg MS-818, respectively, were compared with controls, which received daily intraperitoneal injections of physiological saline, over a 14-day period. The maximum foot-width ratio (crushed side/uncrushed side) was obtained on days 1, 8 and 14 after the crush injury, and the various morphometric parameters were evaluated at both 5 and 10 mm distal to the proximal portion of the crush site. The significant effects of MS-818 included a larger maximum foot width (P<0.04) and a greater number of unmyelinated axons per nerve at both levels (P<0.003) in both test groups than in controls. MS-818 had no significant effects on body weight, the increase of total transverse fascicular area after the crush injury, the total number of myelinated fibers with their size distributions, or the number of nuclei of Schwann cells and macrophages. Therefore, we conclude that MS-818 promotes axonal sprouting and elongation after a crush injury in mice.     

Guillain-Barré syndrome in South-West Stockholm, 1973–1991, 3. Clinicoepidemiological subgroups

Using hierarchical cluster analysis, applied to 47 cases of Guillain-Barre Syndrome (GBS) incident in South-West Stockholm (SWS) during the period from January 1973 to June 1992, we identified three major clinicoepidemiological subgroups. The first subgroup, 25.5% of the cases (26.7 ± 6.7 years), recorded a peak incidence at ages 20–29 years and presented significant differences from other subgroups, a high proportion of cases with onset at low age preceded by respiratory infection (83.3%) and with normal motor conduction velocity (50.0%). Also found, were less affected biological parameters, a rapidly progressive course and independence in gait at one month after onset. A second subgroup, 27.7% of cases, was severely affected, clinically and functionally. It consisted predominantly of young individuals (22.7 ± 11.1 years), with a high incidence (69.2% of cases) in autumn. A third subgroup, comprising 40.47; of cases, was older (61.1 ± 11.0 years) and, in general, also severely affected. The incidence of this form appeared to be invariant with time.     

浅低温心脏不停搏心内手术对心肌保护效果的比较

目的:探讨浅低温体外循环(CPB)心脏搏动中心内直视手术对心肌保护的效果.方法:40例患者随机分为观察组(浅低温心不停搏组)和对照组(中低温心停搏组).分别在术前、转机、停机及术后6 h、12 h、24 h、48 h、72 h,取冠状静脉窦或中心静脉血样,测定血气分析及血清中肌酸磷酸激酶(CK)及其同功酶(CK-MB)、天门冬氨酸氨基转换酶(AST)、乳酸脱氢酶(LDH)、丙二醛(MDA)、超氧化物歧化酶(SOD)的含量.并取心房间隔肌观察心肌含水量及心肌超微结构的改变.临床观察CPB时间、脱机、呼吸支持、多巴胺应用、严重心律失常和血红蛋白尿等指标.结果:冠脉循环血气、电解质、酸碱水平与体循环的组内组间对比基本一致.CK、CK-MB、AST、LDH两组在CPB和术后均有增加,且以对照组升高显著,与观察组相同时点相比,差异均有显著性(P＜0.01).对照组术后MDA明显升高,SOD明显降低(P＜0.01),而观察组变化不大.心肌含水量和超微结构观察,对照组变化显著,而观察组轻微改变.临床指标观察,观察组优于对照组.结论:浅低温体外循环心脏不停搏心内直视手术对心肌损伤很轻,有很好的心肌保护效果.     

从包涵体中纯化重组人幽门螺杆菌热休克蛋白A亚单位

目的：建立一种有效从包涵体中纯化重组人幽门螺杆菌热休克蛋白A亚单位HspA的方法。方法：重组基因工程大肠杆菌发酵后，表达的Hp r HspA包涵体经洗涤，变性，复性，采用Q Sepharose High Performance阴离子交换层析和Superdex75凝胶过滤层析分离纯化，使用SDS－PAGE和HPLC检测纯度，选用ELISA和动物实验对纯化蛋白的免疫学活性和生物学活性进行鉴定。结果：Hp的HspA包涵经洗涤和溶解后，Hp的HspA的纯度＞60％，包涵体溶解液经阴离子交换层析和凝胶过滤层析后纯度超过95％，Hp的HspA纯品经检测具有良好的免疫学活性和生物学活性。结论：本研究建立的分离纯化方法可从包涵体中获得高纯度的重组HspA蛋白，为进一步的动物实验研究奠定了基础。     

冬期淡色库蚊种群生理生态的研究

本文报告作者于1987年5月至1988年9月分别在扬州,上海奉贤等地对冬期淡色库蚊种群生理生态变化的初步研究。结果表明,该蚊在上述地区于10上旬出现滞育,翌年3月上旬开始解除。在上海雄蚊于2月份消失,新蚊于4月中旬出现。冬期各月份都可捕到吸血蚊,吸血蚊生殖营养协调。越冬蚊中大部分未吸血滞育蚊(98%),个别吸血蚊与经产蚊(2%)也可越冬。冬期该蚊具有变换越冬场所以及再次补充营养等现象。     

Hypoxia effects on vascular endothelial growth factor derived epithelial cells of nasal polyps]

OBJECTIVE: To understand the role of nasal mucous epithelial cells to hypoxia in early stage of nasal polyps(NP) formation. METHODS: Epithelial cells of NP and inferior turbinate (IT) were cultured without serum under normal oxygen and hypoxia, and stimulus of inflammatory cytokines. Erythropoietin (EPO) was regarded as hypoxia mark, and expression of vascular endothelial growth factor(VEGF) mRNA and protein derived from epithelial cells were detected respectively by in situ hybridization and ELISA. RESULTS: 1. Under hypoxia, EPO mRNA was expressed intensely in epithelial cells from NP and IT, and there was no significant difference between both of them. This result suggested that EPO might be regarded as a hypoxic mark. 2. The ability of producing VEGF mRNA increased with cytokines stimulation, especially under hypoxia. Protein level of VEGF from epithelial cells of NP and IT increased with cytokines stimulation, especially in hypoxia and was time-dependent. CONCLUSION: Epithelial cells actively produce vast VEGF under hypoxia. The VEGF induced by hypoxia of the mucosa in middle meatus is of importance in the formation of nasal polyps(NP) in early stage, which may be the major cause of NP formation in middle meatus.     

精索静脉曲张患者精索静脉和外周血睾酮水平的对照研究

目的：探讨精索静脉血张患者血浆睾酮水平的变化及其机制。方法：对25例精索静脉曲张患者与22例腹股沟斜疝患者精索静脉和外周血睾酮水平进行对照研究。结果：精索静脉曲张组外周血睾酮浓度与腹股沟斜疝组无差别（P＞0．05），而精索静脉血睾酮浓度两组则有明显差异，精索静脉曲张组精索静脉血中睾酮浓度较腹股沟斜疝组低（P＜0．05）。结论：多种因素可影响外周血睾酮浓度，使其难以准确地反映睾丸分泌睾酮的实际水平，而精索静脉血中的睾酮浓度则能较为直接地反映睾丸的睾酮分泌能力。     

用两株McAb及BA—ELISA法检测肺癌患者血清中肺癌相关抗原

肿瘤患者血清中肿瘤相关抗原含量甚微,通常需要高度敏感的测定系统方能进行检测.生物素-亲和素系统(BSA)是近年来建立的一种生物反应放大系统,由于BSA亲合力高、特异性强反应迅速,故自70年代后期引入免疫技术以来,大大改善和丰富了免疫学试验,成为新的检测系统.本实验用生物素标记两株抗人肺癌McAb——Lc86aE4和Lc86aC5,建立了BA-ELISA方法,并对肺癌患者血清中肺癌相关抗原(lung carcinoma associated antigen,LAA)进行了检测,证实BA-ELISA法具有特异、敏感及重复性好等优点.