急性脑血管病肿瘤坏死因子-α的临床研究

目的：探讨肿瘤坏死因子-α（TNF-α）在急性脑血管病（ACVD）中的作用及其变化的临床意义。方法：选取95例ACVD患者，并设性别及年龄相匹配的血清对照组（20例）及脑脊液对照组（10例）。应用酶联免疫吸附法（ELISA）于发病后第1、3、7、14d测定血清和脑脊液中TNF-α。结果：①三种脑血管病患者血清TNF-α动态变化存在差异，脑出血和脑梗死组的峰值单间为发病后第3d，而蛛网膜下腔出血（SAH）组为第1d。②脑梗死患者血清TNF-α水平与梗死面积、神经功能缺损程度及病情恶化与否相关。③SAH组于发病后第1d、3d、7d脑脊液TNF-α值高于血清，14d时降至对照组水平并与血清无差异。结论：①脑梗死患者血清TNF-α的动态观察，可为临床预测梗死灶大小、神经功能缺损程度及病情恶化与否提供依据。②发病早期的脑梗死患者若CT未能显示病灶时，血清TNF-α的明显升高有助于临床诊断和治疗。③SAH患者脑脊液中TNF-α水平明显高于血清，进一步提示脑内神经组织可产生TNF-α。脑脊液中TNF-α的持续明显升高可能与SAH后脑血管痉挛有关。④TNF-α参与了ACVD的炎性反应过程，早期抑制TNF产生及抗炎性反应的治疗可能具有潜在的临床价值。     

Multidrug transport in human glioblastoma cells is inhibited by transforming growth factors type beta 1, beta 2, and beta 1.2

The transforming growth factors type beta 1, beta 2, and beta 1.2 suppress multidrug transport in human pat-1 glioblastoma cells and even in cells that strongly over-express mdr genes and are resistant to inhibition of multidrug transport by chemosensitizers. Thus, inhibition of multidrug transport by cytokines might be a new approach to increase cellular accumulation of chemotherapeutic agents in multidrug resistant glial tumor cells. Interestingly, a member of the more distantly related decapentaplegic subgroup of transforming growth factors, the bone morphogenetic protein BMP 2, did not inhibit multidrug transport.     

Sources of stress in Australian adolescents: factor structure and stability over time

Adolescent stress is an emerging area of importance in considerations of the health of young people. Exposure to stress predicts a range of both physical and mental health problems in adolescents and relates, as well, to the initiation of important health risk behaviours. Yet the measurement of stress in adolescents has been as fraught with methodological difficulty as it has been for adults. This paper examines the Adolescent Stress Questionnaire (ASQ) which was developed specifically to address the domain of stressors specific to adolescent experience and looks at three cohorts of responses to this questionnaire over time (1995, 1998 and 2001). It assesses the stability of the original 7‐factor structure of the ASQ over time, and while confirmatory factor analysis indicates that stability to be acceptable, it also suggests that either adolescent stressors themselves, or the language by which they are reported, vary sufficiently over time to warrant the refinement of the instrument. Copyright © 2002 John Wiley & Sons, Ltd.     

bFGF对人毛囊黑素细胞增殖、活化和黑素合成作用的研究

目的　研究碱性成纤维细胞生长因子 (bFGF)对人毛囊黑素细胞 (Hairfolloclemelanocyte ,HFM )增殖活化和黑素合成的影响。方法　体外培养正常人HFM ,观察不同浓度bFGF(0 3～ 1 2ng ml)对HFM形态、增殖、酪氨酸酶活性和黑素含量的影响。结果　bFGF处理HFM 7d后 ,HFM树突增多延长 ,酪氨酸酶活性和黑素含量增加显著高于对照组 (P <0 0 1) ,以 0 6ng ml组为著。结论　bFGF能诱导HFM增殖、酪氨酸酶活性和黑素合成增加     

抑制脑血栓形成的硫代磷酸酯脱氧寡核苷酸的亲和性研究

目的为抑制脑血栓形成,合成与TF基因启动子区切应力反应元件(SSRE)形成三链DNA的硫代磷酸酯寡核苷酸(TFO)。方法设计TFO序列14条,采用固相亚磷酰胺三酯固相法合成TFO。硫代磷酸酯修饰在TFO的3'末端进行。应用电泳迁移分析(EMSA)观察寡核苷酸和硫代脱氧寡核苷酸的亲和性。结果在设计合成的14条寡核苷酸中,与靶序列能形成三链DNA的TFO只有T21GTa、T14GTa和T15GTa,其Kd值分别为3.6×10-10、1.0×10-9和1.0×10-8(M),经硫代磷酸酯修饰后分别为:2.3×10-9、3.8×10-9和1.5×10-8。结论硫代磷酸酯修饰的T21GTa-ps、T14GTa-ps和T15GTa-ps能够与TF基因启动子SSRE的3个位点形成三链DNA。     

Ischemic rat brain extracts induce human marrow stromal cell growth factor production

Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain.     

不稳定型心绞痛患者内皮素及血管性假血友病因子的改变

目的 观察不稳定型心绞痛 (Unstableanginapectoris,UAP)患者内皮素 (Endothelin,ET)及血管性假血友病因子 (vonWillebrandfactor,vWF)的变化。方法 不稳定型心绞痛患者34例、正常人21名分别在清晨采血测定ET及vWF值。 结果 不稳定型心绞痛患者ET(129.3±26.4) pg/ml及vWF(185.4±32.4) %值明显高于正常人(85.2±39.6)pg/ml及(142.1±42.0) % ,两者之间不具有显著相关性 (r=0.15,P>0.05)。结论 ET及vWF的改变可能参与了不稳定型心绞痛的病理生理过程。     

SA脂质体介导GFP／bFGF基因在豚鼠耳蜗中的表达

目的 :观察天然碱性脂 (Stearylamine,SA)脂质体介导绿色荧光蛋白 /碱性成纤维细胞生长因子(GFP/bFGF)基因于不同时间段豚鼠耳蜗中的表达 ,为进一步研究耳聋的基因治疗提供实验基础。方法 :取豚鼠 1 6只 ,分成 4组 ,每组 4只。其中 3只右耳圆窗内注入SA -GFP/bFGF复合物 ,1只同法注入生理盐水作为对照。分别于术后第 2、7、1 4、2 1天取材。在荧光显微镜下观察GFP的表达 ,用免疫组化法检测bFGF的转导情况。结果 :荧光显微镜下见双侧耳蜗于术后第 2天开始部分细胞发出绿色荧光 ,第 7天达到高峰 ,支持细胞及内外毛细胞均显荧光 ,细胞轮廓清晰 ;第 1 4天开始减弱 ,第 2 1天消失。免疫组化染色显示 ,除血管纹外 ,耳蜗各回Corti器、螺旋韧带、螺旋缘及螺旋神经节细胞均有高浓度的表达产物 ,对照动物呈阴性表达。结论 :SA脂质体介导的GFP/bFGF基因单耳给药双侧耳蜗均有高效表达 ,为进一步研究基因治疗耳聋提供了可能。     

Chronic treatment with scopolamine and physostigmine changes nerve growth factor (NGF) receptor density and NGF content in rat brain

Nerve growth factor (NGF) and NGF receptors were measured in cortex and hippocampus of rats treated with drugs affecting cholinergic neurotransmission. High (K_d= 0.045nM) and low (K_d= 21nM) affinity¹²⁵I-NGF binding sites were present in both cortical and hippocampal membranes with hippocampus containing higher numbers of both sites than cortex. Chronic treatment of rats with the muscarinic receptor antagonist scopolamine (5 mg/kg, twice daily) decreased the density of high- and low-affinity sites by 50–90% in cortical and hippocampal membranes. These changes were seen after 7 days, but not 3 days, of scopolamine treatment. Chronic infusion of physostigmine (1 mg/kg/day) using minipumps increased the number of high- and low-affinity sites in cortex 3- and 6-fold, respectively. The changes in receptor-binding parameters induced by physostigmine were transient as they were evident after 3 days of treatment, but returned to control levels after 7 days. NGF content in cortex and hippocampus was reduced by about 50% following 7, but not 3, days of chronic physostigmine infusion. In contrast, scopolamine treatment failed to change NGF levels in the cholinergic neuronal target regions but it decreased NGF content in the septal area. The content of NGF mRNA in the cortex measured by Northern blot analysis failed to change following either scopolamine or physostigmine treatment. The results suggest that levels of NGF and NGF receptors in the target regions of cholinergic neurons are regulated by the extent of cholinergic neurotransmitter activity.     

Is neighbourhood deprivation a risk factor for gestational diabetes mellitus?

AIMS: To assess the relationship between neighbourhood deprivation and the rate of gestational diabetes mellitus (GDM) using routinely collected data from a clinical information system, in Plymouth, UK. METHODS: Between 1 January 1996 and 31 December 1997, 3933 women residing within the Plymouth Primary Care Trust (PCT) were screened for GDM using indices of neighbourhood deprivation and prevalence of GDM. Areas (n = 43) were classified according to the Townsend index, measuring material deprivation. Pregnant women with and without GDM were compared. RESULTS: The prevalence of GDM was 1.7%[95%, confidence interval (CI) 1.20, 2.11]. The prevalence of GDM ranged from 1.05% (95% CI 0.60, 1.70) in the most deprived to 2.10% (95%, CI 1.34, 3.13), in the least deprived neighbourhood. Crude rates decreased by 50%[relative prevalence (RP) (95% CI) 0.50 (0.27, 0.94); P = 0.06] amongst those living in the most-deprived compared with those living in the least-deprived areas. Using a stepwise binary logistic regression model, older age at delivery significantly increased the risk of developing GDM. [RP (95%, CI) 1.09, (1.04, 1.13)]. Townsend deprivation score had no significant independent association with GDM when other covariates were considered. CONCLUSION: These data suggest that the neighbourhood context in which women live has no impact on the risk of GDM. Diabet.