细胞间黏附分子-1在实验性自身免疫性脑脊髓炎大鼠中表达的动态变化及作用

目的探讨细胞间黏附分子-1(ICAM-1)在实验性自身免疫性脑脊髓炎(EAE)大鼠中表达的动态变化及其作用。方法分别取免疫后第4、6、8、10、12、14、16、18、20天EAE大鼠脑和脊髓制成石蜡切片,行HE染色和ICAM-1半定量免疫组化分析。结果免疫后第8天ICAM-1表达即出现明显上调,早于临床症状的发生;随免疫后时间的延长,ICAM-1表达呈逐渐增高后缓慢下降的变化趋势,并且与EAE大鼠病情评分呈显著正相关(r=0.57,P=0.003)。结论ICAM-1的表达上调可能在EAE发病中具重要作用。     

A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

人精子体外氧化损伤对线粒体tRNA~(LeuUUR)基因的影响

目的:探讨活性氧(ROS)对人类精子线粒体tRNALeuUUR基因的氧化损伤。方法:采用Percoll梯度离心法筛选具有正常生理功能的精子,作为正常精子模型,并分为损伤组20例和对照组20例,分别加入次黄嘌呤-黄嘌呤氧化酶体系或不予处理,37℃有氧环境中孵育60min。分别提取精子DNA,以Fpg酶切损伤碱基并采用接头介导PCR(LM-PCR)检测线粒体tRNALeuUUR基因的氧化损伤。采用Rhodamine(Rh123)荧光探针标记精子,通过流式细胞仪检测线粒体膜电位,观察精子的功能。结果:与对照组相比,损伤组精子孵育后线粒体膜电位明显降低[(116.27±11.72)%vs(64.00±4.88)%,P<0.05]。Fpg酶切和LM-PCR显示精子线粒体tRNALeuUUR基因损伤。结论:ROS可能通过对精子线粒体tRNALeuUUR基因氧化损伤而影响精子功能(线粒体膜电位明显降低),从而引起不育。     

Cause-specific and total mortality in the Canterbury (New Zealand) insulin-treated Diabetic Registry population: a 15-year follow-up study.

AIMS: To establish all-cause and cause-specific death rates, and risk factors for mortality in insulin-treated diabetic individuals living in the province of Canterbury, New Zealand. METHODS: Insulin-treated diabetic subjects (n = 995) on the Canterbury Diabetes Registry were followed up over 15 years and vital status determined. Death rates were standardized and hazard regression was used to model the effects of demographic covariates on relative survival time. RESULTS: There were 419 deaths in 11 226.3 person-years of follow-up with a standardized mortality ratio (SMR) of 2.0 (95% confidence interval (CI) 1.8-2.2). Relative mortality was greatest for the group aged 0-29 years (SMR 3.0 (95% CI 2.4-3.7)). After controlling for diabetes duration and gender, a 10-year increment in age of onset was associated with a 33% decrease in relative hazard (95% CI 29-36%), indicating that excess mortality due to diabetes declines with rising age of onset. After controlling for age of onset and gender, each 10-year increment in duration of diabetes is associated with a 26% decrease in relative hazard (95% CI 24-29%), indicating that with longer survival the mortality hazard approaches the general population hazard. Relative mortalities were increased for cardiovascular, renal and respiratory disease, but not malignancy. Relative mortality from acute metabolic complications was increased in the subgroup with age of onset of diabetes < 30 years and requiring insulin within 1 year of diagnosis. CONCLUSIONS: Mortality rates are high for insulin-treated diabetic individuals relative to the general population.     

Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation

Campath-1H (alemtuzumab) induction was used for renal transplantation in combination with sirolimus as immunosuppression. We previously reported a high (28%) rate of early rejection with this regimen, and now report 3-year outcomes. Twenty-nine patients were recipients of either deceased donor or non-HLA (Human Leukocyte Antigen) identical living donor primary renal allografts. Clinical parameters including infection, malignancy, kidney function, and kidney histology were followed prospectively for 3 years. Three-year cumulative graft and patient survival were 96% and 100%, respectively. Twenty patients were maintained on steroid-free immunosuppressive regimens, and 15 patients were maintained on monotherapy for immunosuppression (12 on sirolimus). No serious infectious complications were observed and two patients developed basal cell skin cancer. The 3-year results of our initial pilot study demonstrate good graft (96%) and patient (100%) outcomes. Campath-1H induction has yielded a high proportion of patients maintained on immunosuppressive monotherapy (57%) without serious infectious- and no malignancy-related complications. The reported regimen yielded novel insights into both Campath-1H and sirolimus therapy in renal transplantation. Because of the higher incidence of early rejection, we recommend a modified strategy of immunosuppression including a brief course of a calcineurin inhibitor.     

荆州市成人体检血脂及载脂蛋白状况调查与分析

目的:调查荆州市部分成年人体检的血脂和载脂蛋白的水平,为临床血脂研究与心血管病防治提供参考。方法:以2003年至2005年来我院体检的1656名成年人为研究对象,检测其血清中胆固醇(TC)、甘油三酯(TG)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)的含量。结果:TC、TG值随年龄增加而增高,女性比男性增高更明显。男性ApoA1和ApoB值在各年龄段基本一致,女性则是随年龄增加而上升。但在60岁以后又下降。老年前期、老年人血脂异常率较高且比较接近。结论:脂类代谢与年龄密切相关,中老年人尤其是女性血脂异常明显增加,表明动脉粥祥硬化性心血管病的风险明显增高。     

表皮生长因子对牛眼小梁细胞c—fos基因表达的诱导

目的研究表皮生长因子（ｅｐｉｄｅｒｍａｌｇｒｏｗｔｈｆａｃｔｏｒ，ＥＧＦ）对小梁细胞的作用。方法应用分子杂交技术研究ＥＧＦ对体外培养的牛眼小梁细胞ｃ－ｆｏｓ基因表达的诱导和３Ｈ胸腺核苷酸（３Ｈ－ｔｈｙｍｉｄｉｎｅｉｎｃｏｒｐａｒａｔｉｏｎ，３Ｈ－ＴｄＲ）掺入法观察细胞ＤＮＡ的合成。结果小梁细胞的３Ｈ－ＴｄＲ掺入率随着ＥＧＦ浓度不同而变化，浓度为２０～１５０ｎｇ／ｍｌ时，细胞掺入率随浓度增加升高（Ｐ＜０．０１）。与对照组相比，ＥＧＦ刺激停止生长的小梁细胞０．５小时后，ｃ－ｆｏｓ基因开始表达，１小时后达高峰，至２小时后消失。不同浓度ＥＧＦ刺激小梁细胞１小时后，ｃ－ｆｏｓ基因表达呈浓度依赖性。结论实验结果表明ＥＧＦ刺激小梁细胞增殖或进入生长状态，可能与ｃ－ｆｏｓ基因产物的信号传递作用有关。     

Regulation of fibroblast-induced collagen gel contraction by interleukin-1β

Fibroblasts incorporated within collagen gels induce a cell-mediated contraction of the gel to form a three-dimensional, tissue-like structure by a mechanism thought to mimic wound contraction in vivo . In this study a gel contraction model was used to investigate the ability of fibroblasts derived from adult gingiva, adult skin and fetal skin to organise a collagen matrix. In addition the effects of interleukin-1β (IL-1β) on the contraction process was also investigated. Over the concentration range 5-50 U/ml, IL-1β induced a statistically significant inhibition of gel contraction in all fibroblast cell types ( P <0.05), although fetal fibroblasts appeared least responsive and gingival fibroblasts most responsive to the inhibitory effects of this cytokine. Comparison of gel contraction by the different fibroblast strains indicated that fetal and gingival fibroblasts shared similar contraction kinetics. For the adult skin fibroblasts, three of five strains studied showed significantly diminished levels of gel contraction compared to fetal and gingival cells. This apparent difference in fibroblast phenotype may, at least in part, explain the fetal-like wound healing pattern seen in the oral mucosa.     

“Vinylogs” and “Acetylenylogs” of β-Adrenergic Agents

Vinylogous (Groups III and V ) and acetylenologous (Group IV ) analogs of the classical β-adrenergic agents — stimulants and blockers — were prepared in order to evaluate the effect of degree of saturation, position of unsaturation and rigidity of the chain linking the aromatic ring and the amino containing functional group on biological activity. Derivatives from Group III , which represent 4-aryl-3-butenyl-2-ol-amine analogs of Group II , retained β₁-adrenoceptor antagonist activity albeit substantially less potent (50–200-fold) than that possessed by their aryloxy counterparts. Consistent with the SAR for Group II compounds, substitution at position 2 of the aromatic ring yielded the most potent antagonists ( 5a, 5d, 5g ), with K_B's ranging from 73–93 nM while 3,4-dichloro substitution ( 5e ) markedly reduced antagonist potency (K_B = 2,400 nM). Agonist activity was also noted for 5b and 5d , suggesting that these compounds may be best classified as partial agonists. Representatives from Groups IV and V were inactive as antagonists at the β₁-adrenoceptor confirming the importance of the spatial relationship between the hydroxyl and the amino nitrogen.     

nm23-H1基因转染对人胆管癌细胞系QBC939体外浸润能力的影响

目的：探讨nm23-H1基因转染对人胆管癌细胞系QBC939体外浸润能力的影响。方法：将含有全长nm23-H1 cDNA的真核表达载体通过脂腩体法转染人胆管癌细胞系。结果：转染成功的QBC939细胞，其nm23-Hl基因的mRNA、蛋白表达明显增加，转染nm23-H1基因的胆管癌细胞体外浸润能力下降，穿越matrigel的细胞数明显低于亲本QBC939细胞，代表浸润能力的IV型胶原酶（MMP-9）分泌量下降。结论：nm23-Hl基因可以抑制胆管癌细胞的体外浸润能力。