甲状腺乳头腺瘤中EGFR,nm—23—H1和p53蛋白的表达

目的：探讨ＥＧＦＲ、ｎｍ２３－Ｈ１及ｐ５３蛋白在甲状腺乳头状腺癌中的表达及其与淋巴结转移的关系。方法：应用免疫组化ＡＢＣ法检测３６例有颈淋巴结转移的甲状腺乳头状腺瘤的原发灶与转移灶和４０例无转移的甲状腺乳头状腺癌中ＥＧＦＲ、ｎｍ２３－Ｈ１和ｐ５３蛋白的表达。结果：７６例甲状腺乳头状腺癌的ＥＧＦＲ、ｎｍ２３－Ｈ１及ｐ５３蛋白的阳性表达率分别为５５．３％、６０．５％和１１．８％；但有转移的甲状腺乳头状     

c-erbB-2、p53、bcl-2和nm23-H1在肺癌中的表达

目的：探讨ｃｅｒｂＢ２、ｐ５３、ｂｃｌ２和ｎｍ２３Ｈ１基因在肺癌发生发展过程中的作用。方法：用免疫组化ＡＢＣ法对原发性肺癌组织中４种基因的表达和突变进行检测。结果：５８例肺癌中,３１例（５３４５％）ｐ５３过度表达,１８例（３１０３％）ｂｃｌ２过度表达。ｃｅｒｂＢ２与ｎｍ２３Ｈ１在１０例小细胞肺癌（ＳＣＬＣ）中未见表达。而在４８例非小细胞肺癌（ＮＳＣＬＣｓ）中两者过度表达率均为５０％。ｃｅｒｂＢ２与ｎｍ２３Ｈ１表达呈正相关（Ｐ＜００５）。腺癌ｎｍ２３Ｈ１的表达明显高于鳞癌（Ｐ＜００５）。ｐ５３、ｂｃｌ２蛋白表达在肺癌分化程度中呈负相关（Ｐ＜００５）。ｎｍ２３Ｈ１、ｐ５３和ｂｃｌ２的表达与患者的生存率有关（Ｐ＜００５）。结论：ｃｅｒｂＢ２、ｐ５３、ｂｃｌ２和ｎｍ２３Ｈ１基因蛋白产物的检测对肺癌患者的诊治和预后评估有积极意义。     

nm23-H1、p53、PCNA表达与大肠癌浸润转移的关系

目的：研究大肠癌中ｎｍ２３－Ｈ１、ｐ５３、ＰＣＮＡ的表达与浸润转移的关系。方法：应用ＬＳＡＢ免疫组织化学方法检测７４例大肠癌中ｎｍ２３－Ｈ１、ｐ５３、ＰＣＮＡ和Ⅳ型原的表达。结果：大肠癌中ｎｍ２３－Ｈ１、ｐ５３和ＰＣＮＡ的阳性率分别为７１．６％、５２．７％和８１．１％。大肠癌中ｎｍ２３－Ｈ１低表达与淋巴结转移有关（Ｐ＜０．０２５），ｎｍ２３－Ｈ１的表达在Ⅳ型胶原表达不同的肠癌中无明显差异（Ｐ＞０．０５）；ｐ５３和ＰＣＮＡ过表达与浸润程度和淋巴结转移有关（Ｐ＜０．０５），ｐ５３和ＰＣＮＡ的表达在Ⅳ型胶原表达不同的肠癌中有非常显著的差异（Ｐ＜０．００５）；大肠癌中ｐ５３过表达与ｎｍ２３－Ｈ１低表达有关（Ｐ＜０．０１）。结论：实验结果揭示ｐ５３基因突变对于ｎｍ２３－Ｈ１基因的失活有一定影响，其作用机制有待深入研究。ｎｍ２３－Ｈ１低表达可能仅在大肠癌转移过程中发挥作用，ｐ５３过表达可在大肠癌浸润转移过程及细胞增殖中起重要作用。     

p53和nm23联合表达对食管鳞癌淋巴结转移的影响

目的：探讨ｐ５３ 和ｎｍ２３ 表达作为食管鳞癌转移标志物的实用价值。方法：采用免疫组化方法检测８５ 例原发性食管鳞癌中ｐ５３ 和ｎｍ２３ 蛋白表达。结果：６３－５３ ％ （５４／８５） 肿瘤呈ｐ５３ 阳性表达,ｐ５３ 阳性表达与肿瘤淋巴结转移和ＴＮＭ 分期有关（Ｐ值均为０－００１）。４０ ％（３４／８５） 肿瘤为ｎｍ２３ 低表达。ｎｍ２３ 低表达与肿瘤浸润深度、淋巴结转移、ＴＮＭ 分期有关（ Ｐ值分别为０－０３２、０－００１、０－００１） 。单因素分析显示：ｐ５３ 和ｎｍ２３ 表达为影响淋巴结转移的主要因素（ ＯＲ值分别为６－９８４ 和０－０８７,Ｐ＜０－００１）。多因素分析显示：ｎｍ２３ 表达是影响淋巴结转移的一个独立因素（珘ｂ＝ － ０－８４８１ , ＯＲ＝ ０－１８１, Ｐ＝ ０－０００１） 。ｐ５３阳性肿瘤具有高度淋巴结转移的倾向（珘ｂ＝ ０－３１５０, ＯＲ＝２－２８４,Ｐ＝ ０－０５６５）,其它临床病理学参数与淋巴结转移之间未见明显关系（Ｐ＞ ０－０５） 。ｐ５３ 和ｎｍ２３ 异常表达之间呈负相关（ｒｓ＝ － ０－３８４９ ,Ｐ＝ ０－０００３）,在促进肿瘤的进展和转移过程中起联合作用。结论：ｐ５３ 和ｎｍ２３ 联合表达对判断食管鳞癌患者     

大肠癌表皮生长因子受体和p53蛋白表达与临床病理特征和预后的关系

为了研究大肠癌表皮生长因子受体（ＥＧＦＲ）和ｐ５３蛋白表达与病理特征和预后的关系，应用免疫组化检测ＥＧＦＲ和ｐ５３在６１例大肠癌中的表达。结果提示：正常大肠粘膜未发现ＥＧＦＲ和ｐ５３阳性表达，而两者在大肠癌均有较高表达（７７．０４％和５５．７５％）。ＥＧＦＲ表达与大肠癌Ｄｕｋｅｓ分期有关（Ｐ＜０．０５）。ｐ５３表达与大肠癌分化程度及Ｄｕｋｅｓ分期有关（Ｐ＜０．０５）。大肠癌生存率随ＥＧＦＲ和ｐ５３表达增高而降低，其中两者４年生存率＞６５％表达组均明显低于＜２５％组（Ｐ＜０．０５），ＥＧＦＲ－ＬＩ和ｐ５３－ＬＩ与生存期均有明显负相关。结果表明：ＥＧＦＲ和ｐ５３表达与大肠癌的进展程度有关，该两项指标对大肠癌临床诊治和预后的评估有重要价值。     

p53、ras p21、c-erbB-2和nm23在肺癌组织中的表达

目的：探讨癌基因与肺癌临床病理特征及预后的关系。方法：应用免疫组化ＳＰ法对５８ 例肺癌行ｐ５３、ｒａｓｐ２１、ｃｅｒｂＢ２和ｎｍ２３ 的检测。结果：癌组织中阳性反应检出率分别为４６－６％ 、２４－１ ％ 、５０－０ ％ 和５３－４ ％ ,腺癌和差分化癌ｒａｓ ｐ２１ 、ｃｅｒｂＢ２表达高于鳞癌和分化好的癌（ Ｐ＜ ０－０５） ,术后长期生存患者ｒａｓｐ２１ 、ｃｅｒｂＢ２ 表达低于短期死亡患者（Ｐ＜ ０－０５ ,Ｐ＜ ０－０１）,吸烟患者ｒａｓ ｐ２１ 表达高于不吸烟患者（Ｐ＜ ０－０５） ,淋巴结癌转移阴性组ｎｍ２３ 表达高于淋巴结癌转移阳性组（ Ｐ＜ ０－０１）,ｐ５３ 与ｒａｓ ｐ２１、ｃｅｒｂＢ２ 阳性表达具有协同性（ Ｐ＜ ０－０５） 。结论：肺癌发生发展和转移与ｒａｓｐ２１ 、ｃｅｒｂＢ２ 的激活和ｐ５３ 、ｎｍ２３ 的失活密切相关,部分基因的改变存在协同性,ｒａｓ ｐ２１ 基因的激活与吸烟有关,ｒａｓ ｐ２１、ｃｅｒｂＢ２ 的检测对判断肺癌预后有价值。     

p53、EGFR和Ki-67抗原在子宫恶性中胚叶混合瘤中的表达

目的：研究子宫恶性中胚叶混合瘤ｐ５３、ＥＧＦＲ和Ｋｉ－６７抗原的表达及与肿瘤临床分期、组织学分级和预后的关系。方法：用免疫组化Ｓ－Ｐ法对２１例子宫恶性中胚叶混合瘤的存档资料作染色观察。结果：ｐ５３、ＥＧＦＲ和Ｋｉ－６７抗原的阳性表达率分别为６１．９％、６１．９％和７１．４％。临床分期Ⅱ～Ⅳ期肿瘤（１０／１２）的ｐ５３阳性表达率明显高于Ⅰ期肿瘤（３／９）（Ｐ＜０．０５）、肿瘤癌性成分Ⅱ级的ｐ５３阳性表达高于Ⅰ期（Ｐ＜０．０５）。６例在１年内死亡的病例，其中５例ｐ５３阳性染色，而５例生存２年以上的肿瘤ｐ５３免疫染色全部阴性，两组比较（Ｐ＜０．０５）。肉瘤成分Ⅲ级的ＥＧＦＲ阳性率高于Ⅱ级（Ｐ＜０．０５），除此而外，ＥＧＦＲ和Ｋｉ－６７的表达和肿瘤分期、预后均无相关性。结论：肿瘤的ｐ５３表达具有预后意义     

胃癌p53、nm23和EGF-R蛋白表达与临床病理特征的关系

目的：探讨ｐ５３、ｎｍ２３和ＥＧＦ－Ｒ蛋白表达与胃癌临床病理特征的关系。方法：运用免疫组织化学方法研究５７例胃癌、２０例异型增生和２０例肠上皮化生和１０例正常胃粘膜ｐ５３、ｎｍ２３和ＥＧＦ－Ｒ蛋白的表达。结果：正常胃粘膜三种蛋白均阴性，肠上皮化生ｐ５３和ｎｍ２３均未表达，而ＥＧＦ－Ｒ阳性率为５％。异型增生和胃癌组织中ｐ５３阳性率分别为１５％和５４．４％；ｎｍ２３阳性率分别为５％和６３．２％；ＥＧＦ     

大肠癌表皮生长因子受体和p53蛋白表达与临床病理特？…

为了研究大肠癌表皮生长因子受体（ＥＧＦＲ）和ｐ５３蛋白表达与病理特征和预后的关系，应用免疫组化检测ＥＧＦＲ和ｐ５３在６１例大肠癌中的表达，结果提示：正常大肠粘膜未发现ＥＧＦＲ和ｐ５３阳性表达，而两者在大肠癌均有较高表达（７７．０４％和５５．７５％）。ＥＧＦＲ表达与大肠癌Ｄｕｋｅｓ分期有关（Ｐ〈０．０５）。ｐ５３表达与大肠癌分化程度及Ｄｕｋｅｓ分期有关（Ｐ〈０．０５）。大肠癌生存率随ＥＧＦＲ和ｐ５３     

转化生长因子β1、表皮生长因子受体表达与非小细胞肺癌淋巴结转移及预后的关系

目的：探讨转化生长因子β１（ＴＧＦβ１）、表皮生长因子受体（ＥＧＦＲ）在非小细胞肺癌中的表达及意义。方法：应用免疫组化法检测了１２１例非小细胞肺癌标本中ＴＧＦβ１、ＥＧＦＲ的表达。结果：ＴＧＦβ１在肺癌中的阳性表达分为间质型和胞浆型,总阳性表达率为７７．７％。ＴＧＦβ１的阳性表达类型与肺癌的淋巴结转移及预后有关,淋巴结转移阳性组ＴＧＦβ１的单一间质阳性表达率显著低于淋巴结阴性组,而单一胞浆阳性表达率高于淋巴结阴性组;半年内死亡组的ＴＧＦβ１单一间质阳性表达率低于５年以上生存组,而间质胞浆均阳性的表达率及单一胞浆阳性表达率则高于５年以上生存组（Ｐ均＜０．０５）。ＥＧＦＲ阳性表达率为４３．８％,其表达与淋巴结转移无关;与患者预后关系明显,ＥＧＦＲ阳性表达者预后差（Ｐ＜０．０５）。结论：ＴＧＦβ１、ＥＧＦＲ表达与肺癌恶性生物学行为关系明显,是评估患者预后的有效参数     

RAS蛋白在胶质瘤中的表达及其对胶质瘤细胞生长的影响

目的 探讨RAS蛋白在胶质瘤中的表达及其对人脑胶质瘤细胞生长的影响.方法 用免疫组化染色法检测RAS蛋白在正常脑组织及各级别胶质瘤组织中的表达水平,并采用四甲基偶氮唑盐微量酶反应比色法和流式细胞技术检测降低RAS活性后U251细胞的增殖和凋亡情况;用Western印迹法检测ERK和AKT信号通路.结果 胶质瘤组织中RAS的表达随胶质瘤恶性程度增高而增强.抑制RAS 蛋白活性后,RAS信号通路的下游分子ERK和AKT蛋白磷酸化水平降低;U251胶质瘤细胞生长受抑制,细胞生长阻滞在G1期且凋亡增加.结论 RAS蛋白在胶质瘤中高表达,抑制其活性可下调ERK和AKT 信号通路,进而调控细胞的生长.     

Isolation of human C-reactive protein and serum amyloid P component

Procedures are described for the isolation in high yield of consistent, highly purified preparations of human C-reactive protein (CRP) and serum amyloid P component (SAP). CRP was obtained from malignant ascitic and pleural fluids by calcium-dependent affinity chromatography on pneumococcal C-polysaccharide covalently coupled to cyanogen bromide-activated Sepharose. It was then gel filtered on Ultrogel AcA44 (acrylamideagarose beads) in the presence of calcium ions, combining molecular sieve chromatography with removal of contaminating SAP by its affinity for agarose. Residual trace contaminants were removed by immunoabsorption with anti-normal human serum and anti-SAP antibodies insolubilised on Sepharose and/or by absorption with Sepharose-Con A to remove glycoproteins and Blue-Sepharose to remove albumin. After a final gel filtration step on Sephacryl S-300 35–44% of the initial CRP was recovered in pure from according to biochemical and immunochemical criteria. SAP was isolated from normal serum by calcium-dependent affinity chromatography on unsubstituted Sepharose beads, followed by solid-phase immunoabsorption of contaminants and finally gel filtration on Sephacryl S-300. At least 50% of the SAP in the starting material was recovered in pure form according to biochemical and immuunochemical criteria. Ready availability of such preparations facilitates biochemical, biophysical and particularly biological studies of these plasma proteins.     

The concentration of the C-type lectin, mannan-binding protein, in human plasma increases during an acute phase response.

Two ELISAs for estimating mannan-binding protein (MBP) were constructed and the concentration of MBP in plasma was followed in patients undergoing major surgery and in patients having a malarial attack. In both cases increases of MBP in the plasma were observed. The relative increase and the kinetics varied from person to person. The concentration of MBP increased between 1.5- and three-fold following surgery. In some patients an increase was seen at day 1 whereas in others the increase was not observed until days 3-9. In the malaria patients an increased level of MBP was maintained during 30 days of treatment with chloroquine. The relative increase in MBP was independent of the presurgery or premalaria levels.     

Binding of mannan-binding protein to various bacterial pathogens of meningitis

Mannan-binding protein (MBP), a calcium-dependent plasma lectin, may play a role in the innate defence against microorganisms. After binding lo carbohydrate structures at the bacterial surface, MBP activates the classical pathway of the complement system. To investigate the binding capacity of MBP to various bacteria associated with meningitis, an assay was developed to study the binding of MBP to bacteria grown in a semisynthetic fluid culture medium. Salmonella montevideo (containing a mannose-rich lipopolysaccharide (EPS)), used as a positive control strain, showed binding of radiolabelled MBP at a level of 80% compared with binding of MBP to zymosan. Binding of labelled MBP to Salm. montevideo was time-dependent, temperature-dependent and saturable. The binding, was inhibited by unlabelled MBP., by mannose and by N-acetyl-o-glucosamine. Among bacterial pathogens often found to cause meningitis, a wide range of MBP binding capacities could be determined. The encapsulated Neisseria meningitidis (representatives from 11 serogroups other than group A were included: n = 22), N. mucosa (n = 1), Haemophilus influenzae type b (n = 10) and Streptococcus agalactiae (n = 5) had a low MBP binding capacity of 21.7% (95% confidence interval (Cl) 3.3–40.1%). Escherichia coli K1 (n =11). Strep, suis (n = 5), Strep, pneumoniae (n = 10) and N. meningitidis scrogroup A (n = 2) showed intermediate MBP binding capacity of 58.4% (95% Cl 40.0–76.8%). A third group consisting of non-encapsulated Listeria monocytogenes (n = 11), non-encapsulated H. influenzae (n = 2), non-encapsulated N. meningitidis (n = 2), N. cinera (n = 1) and N. subflava (n = 1) strains had a high MBP binding capacity of 87.5% (95% CI 62.5–12.5%). The majority of encapsulated pathogens causing bacterial meningitis seem to have a rather low MBP binding capacity.     

β淀粉样蛋白对大鼠学习记忆功能及tau蛋白异常磷酸化的影响

为了探讨β淀粉样蛋白对大鼠学习记忆功能和tau蛋白异常磷酸化的影响,本文在海马注射Aβ25-35建立阿尔茨海黙病(AD)大鼠模型的基础上,通过行为学检测、HE染色、免疫组化和免疫蛋白印迹技术对动物的学习能力、组织的病理改变和tau(pS202)、tau(pT231)和tau-5的表达情况进行了分析。在行为学检测中,Aβ注射组大鼠在穿梭箱实验中的主动回避次数和被动回避次数减少,失败次数增多,而在Morris水迷宫测试中的逃避潜伏期和游泳距离延长。HE染色显示Aβ注射组大鼠海马CA1、CA3、齿状回的神经细胞数目减少;而免疫组化和免疫印迹结果显示注射组tau(pS202)阳性细胞明显增加,tau(pS202)、tau(pT231)和tau-5蛋白表达增加。以上结果提示海马内注射Aβ25-35可引起大鼠学习记忆功能下降,可能与神经细胞减少,tau蛋白异常磷酸化增多有关。     

Lack of binding between cryoimmunoglobulins, immunoglobulins and fibronectin: implications for immune complex vasculitis

Immune-complex-mediated vasculitis is a frequent complication of rheumatoid arthritis and systemic lupus erythematosus. The mechanism of deposition of immune complexes within the vessel wall in these diseases remains unknown, but probably involves other proteins. Fibronectin is a likely candidate since it possesses the ability to bind to collagen, endothelial cells, and possibly immunoglobulins and immune complexes. In this study, the binding of fibronectin to IgG and IgM cryoglobulins, cold soluble IgM, IgG, IgG subclasses and IgG fragments was investigated in the solution phase. Static light scattering, fluorescence anisotropy, fluorescence intensity, and PEG precipitation studies were used to investigate binding under different conditions of temperature and ionic strength. These studies failed to demonstrate significant binding between fibronectin and IgM, IgG, IgG subclasses and IgG fragments under the conditions studied. These findings argue against solution phase binding of fibronectin and immunoglobulins contributing to immune complex vasculitis. The possibility of important surface interactions between these proteins has not been ruled out.     

上皮钙黏蛋白、波形蛋白和Snail蛋白表型在乳腺浸润性导管癌中表达的相关性及其与预后的关系

目的 检测上皮钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)和Snail蛋白在乳腺浸润性导管癌中的表达情况与乳腺癌病理特征的关系及其与浸润性导管癌预后的关系.方法 采用Envision免疫组织化学方法对89例乳腺浸润性导管癌组织中的上E-cadhenn,Vimentin和Snail蛋白表达情况进行检测并分析表达程度与临床病理特征之间的关系;统计分析采用卡方检验、Fisher精确概率法检验Spearman等级相关检验、配对计数资料检验、Kaplan-Meier法进行单因素生存分析,Cox比例风险模型进行生存的多因素分析.结果 E-cadherin、Vimentin和Snail蛋白在浸润性导管癌组织中的阳性表达率分别为、47.1％、53.9％和55.0％,三者呈负相关,(P=0.003);E-cadherin、Vimentin和Snail蛋白的表达与临床TNM分期有关(P ＜0.005).浸润性导管癌中Snail蛋白、Vimentin表达明显增高,Snail蛋白与淋巴结转移有关(P =0.029);Vimentin与淋巴结转移、雌激素状态有关(P =0.006,P＜0.001);E-cadherin表达明显降低,与孕激素状态有关(P =0.030);分子分型结果显示,管腔A型、HER-2阳性型组的Vimentin、Snail蛋白阳性表达率低于基地细胞样型组(P =0.012),而E-cadherin表达率则高于基地细胞样型组(P =0.004).Cox分析发现,E-cadherin低表达和Vimentin的过度表达与患者总生存期(P =0.019、P=0.045)及患者无病生存期(P =0.032、P=0.024)显著相关,但Snail蛋白的表达与总生存期及无病生存期无相关性(P =0.879、P=0.835).结论 E-cadhern、Vimentin和Snail蛋白在乳腺浸润性导管癌的发生、发展、侵袭及转移中起重要作用,对认识乳腺癌的生物学特性以及对指导乳腺癌的诊疗及预后具有重要意义.     

Eosinophil cationic protein and eosinophil protein X in the nasal lavage of children during the first 4 weeks of life. SPACE Collaborative Study Team

Eosinophil cationic protein (ECP) and eosinophil protein X (EPX) are well established as markers of eosinophil activation. We analyzed ECP and EPX concentrations in nasal lavage fluids (NALF) of 378 neonates during their first 4 weeks of life. Inclusion criteria were a positive history of parental allergy and a positive skin prick test or specific IgE (RAST class > or = 2) against at least one out of a panel of common aeroallergens in one or both parents. Twenty-four infants with no history of parental allergy were used as controls. A volume of 2 ml of 0.9% saline was instilled into each nostril and immediately recovered by a suction device. ECP and EPX were analyzed by radioimmunoassay. In 65 samples of three consecutive lavages, EPX was detected in nine samples (13.8%) in the control group, whereas it was detected in 197/360 samples (54.7%) in the study population. The corresponding figures for ECP were 17/65 (26.2%) in the control group and 173/365 (47.4%) in the study group. Both proteins showed a skewed distribution (median/5-95th percentiles for ECP: 0 microg/l [0-69.4] and EPX: 6.6 microg/l [0-73.2]). The differences between the control group and the study group were statistically significant, regardless of the allergic disease of the parents. In children of allergic parents, activation proteins of the eosinophil granulocyte are released on the nasal mucosal surface in about 50% of the studied population at the age of 4 weeks. This early onset of eosinophil activation in the nasal respiratory epithelium may reflect a genetic predisposition to allergy or early exposure to allergens.     

La蛋白质家族与肿瘤关系

La蛋白相关家族(La-related proteins,LARPs)包括LARP1、LARP1b、LARP3,(Genuine La)、LARP4a、LARP4b、LARP6和LARP7.LARPs结构包含中度保守的RNA识别模体(RNA recognition motif,RRM)和多个其他结构、运输元件,可定位于不同的亚细胞部位与RNA相互作用,在细胞转录和翻译等方面发挥重要的作用.人LARPs最初是在系统性红斑狼疮和Sjogren's综合征患者的血清内发现的自体抗原,目前随着研究深入普遍认为LARPs作为一种RNA分子伴侣参与RNA代谢能发挥多种生物学功能.此前国内有学者研究验证LARPs能稳定乙型肝炎病毒(hepatitis B virus,HBV)的mRNA,帮助其在肝细胞中复制与翻译,在乙型肝炎进展中具有重要作用.近年发现,LARPs在多种恶性肿瘤如子宫颈癌、乳腺癌、肝癌和前列腺癌等的细胞增殖、分化、迁移、血管形成的调节等方面起重要作用.而恶性肿瘤的发生与演进是由环境与遗传因素相互作用而导致的许多基因突变,实际上基因突变产生的编码蛋白质执行细胞生命活动,因而LARPs在肿瘤中扮演的分子角色将可能在肿瘤的诊断与治疗中提供潜在的新靶点、新策略和新途径.