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1.
人IL-4基因修饰增强瘤细胞特异性CTL杀伤活性机制初探   总被引:1,自引:0,他引:1  
目的 探讨IL-4基因修饰瘤苗增强细胞毒性T淋巴细胞(CTL)杀伤活性的机制。方法 通过逆转录病毒载体pL-IL-4-SN将人IL-4基因导入肝癌细胞系HepG2细胞,以IL-4基因修饰瘤苗和野生型瘤细胞作刺激细胞诱导CTL反应,通过流式细胞仪检查肿瘤细胞表面分子表达。结果 IL-4基因修饰诱导瘤细胞表达MHCⅡ类抗原、B7-1及ICAM-1等细胞表面分子,对MHCⅠ类抗原表达无影响,其瘤苗诱导的CTL杀伤活性为罢生型瘤细胞的7倍(P<0.01),加入抗IL-4单克隆抗体(McAb)可完全阻断IL-4诱导的细胞表面分子表达,IL-4基因修饰瘤苗诱导CTL反应时培养上清可测及大量IL-2产生,抗IL-4或抗细胞表面分子的McAb可降低IL-2产生及抑制CTL反应。结论 IL-4基因修饰可能是通过诱导MHCⅡ类抗原等表达分子表达,促进IL-2产生而增强CTL杀伤活性。  相似文献   

2.
Li Y  Mi C  Wu YZ  Yang SF  Yang ZQ 《中华病理学杂志》2004,33(6):546-549
目的 通过 genistein对人卵巢癌细胞系SKOV3 及其裸鼠移植瘤中表皮生长因子受体(EGFR)介导的肿瘤信号转导系统的影响 ,探讨其抑制增殖作用的机制。方法 应用免疫细胞化学链霉素抗生物素蛋白过氧化物酶 (SP)法检测c erbB 2蛋白的表达 ;Western印迹检测细胞c jun和c fos蛋白的表达 ;逆转录 聚合酶链反应 (RT PCR)检测c erbB 2 ,c raf 1,c jun和c fosmRNA的表达。结果  2 0 μmol/Lgenistein处理组c erbB 2、c raf 1及其下游基因c jun、c fosmRNA表达减弱。2 0 μmol/Lgenistein处理SKOV3 细胞 4 8h后 ,c erbB 2蛋白表达减弱 ,平均吸光度 (A)值减低 ,为0 4 2± 0 0 2 (P <0 0 5 )。Western印迹检测结果表明 :2 0 μmol/Lgenistein处理SKOV3 细胞 12~ 72h后 ,c jun、c fos蛋白表达水平逐渐减弱。结论 genistein下调SKOV3 中EGFR介导的肿瘤信号转导通路中两个关键基因c erbB 2和c raf 1之mRNA及蛋白及其下游核转录因子c jun和c fos的mRNA及蛋白的表达水平 ,提示genistein干预EGFR介导的肿瘤信号转导系统中主要信号分子的表达可能是其抑制卵巢癌增殖的分子基础。  相似文献   

3.
IL-4基因转染诱导肝母细胞瘤分化及抑制端粒酶活性   总被引:5,自引:0,他引:5  
目的 研究人白细胞介素4(human interleukin-4,hIL-4)基因转染对肝母细胞瘤细胞的诱导分化和对端粒酶活性的影响。方法 以逆转录病毒载体(PL-IL-4-SN)将hIL-4基因导入人肝母细胞瘤细胞系Hep G2细胞。台盼蓝拒梁,放射免疫测定,流式细胞仪细胞周期分析,原位杂交,PCR-ELISA等方法检测基因转染后细胞形态,甲胎蛋白合成,原癌基因的表达及端粒酶活性变化。  相似文献   

4.
探讨c junN terminal激酶 (JNK)在胆红素诱导人神经母细胞瘤SH SY5Y细胞凋亡信号转导中的作用。我们用 30 0 μmol LH2 O2 预处理SH SY5Y细胞 1h以激活JNK ,与经PBS预处理的对照组比较 ,流式细胞仪结果显示凋亡细胞百分比由 (37 4± 3 2 ) %降低到 (12 6± 2 6 ) %。为了进一步证实JNK的作用 ,在SH SY5Y细胞经H2 O2 预处理前 ,先经 2 0 μmol LJNK c jun AP1抑制剂curcumin作用 12h以抑制H2 O2 对JNK的激活 ,流式细胞仪结果显示凋亡细胞增高到 (42 8± 4 4 ) % ,curcumin完全抑制了短暂激活JNK所提供的保护作用。结果表明短暂激活JNK可能在胆红素诱导的SH SY5Y细胞凋亡中提供抗凋亡信号 ,提示激活JNK可保护神经细胞  相似文献   

5.
目的 :观察三七总皂甙是否能诱导人白血病细胞株HL 60细胞凋亡及相关基因的关系。方法 :取 2 0 0~ 1 60 0ug/ml三七总皂甙处理HL 60细胞 ,光镜下观察细胞形态 ;MTT法测细胞生长抑制率 ;流式细胞仪检测细胞周期 ;免疫组化法检测 p5 3 ,bcl 2凋亡相关基因的表达 ,采用真彩色图像分析仪定量分析免疫组化的结果 ;其结果表明 2 0 0~ 1 60 0ug/ml三七总皂甙可抑制HL 60细胞生长 ,抑制率随着剂量的增加而增加。流式细胞仪检测凋亡峰随药物浓度增大而增加。80 0 ,1 60 0ug/毫升三七总皂甙可使 p5 3基因表达上调 ,bcl 2表达明显下降 ,这两种基…  相似文献   

6.
子宫颈癌中癌基因产物c—Fos、c—Jun的表达及意义   总被引:3,自引:0,他引:3  
目的 :探讨癌基因c fos、c jun表达产物与子宫颈癌的发生 ,发展及预后的关系。方法 :用免疫组化SABC法 ,以兔抗c fos、c jun抗体标记 6 0例子宫颈癌和 30例子宫颈上皮不典型增生 ,观察其分化程度和组织学类型 ,子宫颈癌的表达及阳性率比较。结果 :c fos、c jun阳性反应见于不典型增生上皮和子宫颈癌组织 ,不典型增生上皮c fos、c jun阳性率分别为 70 0 %和 5 0 0 %癌组织为 5 6 6 %和 4 8 3% ;在子宫颈癌表达的阳性率与癌组织分化程度和组织学类型有关 (P <0 .0 5 )。结论 :提示c fos、c jun过量表达可发生在不典型增生的子宫颈上皮和子宫颈癌组织  相似文献   

7.
目的 探讨体外用细胞因子诱导实体瘤细胞生成具有树突状细胞样的抗原提呈功能。方法 以人肝母细胞瘤为研究模型 ,用人胰岛素样生长因子 (IGF 1)、人重组粒细胞单核细胞集落刺激因子 (GM CSF)、人重组白细胞介素 4 (IL 4 )及肿瘤坏死因子α(TNF α)诱导培养瘤细胞 2周 ,用流式细胞仪及MTT法检测诱导前后瘤细胞表型及抗原提呈功能。结果 用细胞因子处理瘤细胞后 ,树突状细胞样的特异性标志CD1a和CD83表达阳性率显著上调 ;MHCⅡ、B7 1、B7 2、ICAM 1和CD4 0表达水平显著增加。同时 ,瘤细胞能显著刺激同种异体淋巴细胞增殖 ,促进IL 12的产生 ,明显提高细胞毒性T淋巴细胞 (CTL)对瘤细胞的杀伤活性。结论 初步实验结果提示 ,体外用IGF 1、GM CSF、IL 4及TNF α等细胞因子能诱导肝母细胞瘤细胞生成具有树突状细胞样特征的抗原提呈细胞。  相似文献   

8.
p16INK4A和 p15INK4B对人肝癌细胞增殖和凋亡影响的研究   总被引:8,自引:0,他引:8  
目的 为探讨抑癌基因 p16 INK4 A和 p15 INK4 B对 Rb基因状态不同的人肝癌细胞系增殖和凋亡的影响。方法 在分析细胞系遗传背景鉴定基础上采用脂质体将构建的 p XJ- p16、p XJ- p15重组质粒转染人肝癌细胞系 BEL74 0 2 (p16 / p15 Rb )和 SMMC772 1(p16 / p15 / Rb- )。应用 PCR、RNA斑点印迹、MTT、集落形成、流式细胞仪等技术检测外源性 p16和 p15基因、m RNA表达及其对肝癌细胞增殖、凋亡的影响。结果 经转染的 BEL74 0 2 - p16 ,BEL74 0 2 - p15细胞 ,分别存在外源性 p16、p15基因 ,在含外源基因细胞中相应的 m RNA表达增强 ;BEL74 0 2 - p15细胞生长速度、集落形成率显著低于对照细胞 BEL 74 0 2 (P<0 .0 1) ;细胞周期分析观察到与亲本细胞比较 ,BEL 74 0 2 - p15的 G1期细胞由 37.7%增高到 4 3.6 % ,S期细胞由 2 2 %下降到 13% (P<0 .0 5 ) ,并出现 G1亚峰 (凋亡峰 )。与此相反 ,BEL74 0 2 - p16细胞增殖未见抑制 ,细胞周期分布无明显差异 ,集落形成率也未见减少。此外 ,SMMC772 1- p16细胞增殖也无抑制。结论 外源性 p15 INK4 B具有抑制人肝癌细胞生长 ,诱导细胞凋亡的作用 ,其作用不受内源性p15影响。而 p16 INK4 A对肝癌细胞生长抑制的作用可能依赖于 RB途径的完整性。  相似文献   

9.
白色念珠菌诱导小鼠胸腺细胞凋亡的基因调控   总被引:1,自引:0,他引:1  
目的 探讨白色念珠菌诱导小鼠胸腺细胞凋亡过程中的基因调控作用。方法 经小鼠尾静脉注射白色念珠菌后 ,采用FCM技术测定胸腺凋亡细胞上 5个凋亡相关基因 ( p5 3,bax ,bcl 2 ,fas和c myc)产物的水平在不同时间组的变化。结果 p5 3和bax两个基因产物的水平明显增加 ;而bcl 2 ,fas和c myc基因产物的水平无明显改变。 结论 白色念珠菌诱导小鼠胸腺细胞凋亡 ,可能是经由基因调控的转录途径机制而发生 ,p5 3和bax基因在此过程起重要作用  相似文献   

10.
RNAi沉默WT1基因对人肝癌细胞HepG2的影响   总被引:1,自引:1,他引:0  
目的:探讨利用RNA干扰沉默WT1基因对人肝癌细胞HepG2细胞生长,凋亡的影响,为肝癌的基因治疗提供理论依据。方法:利用脂质体将siRNA真核表达载体转入HepG2细胞中,并检测转染效率;利用免疫细胞化学染色方法检测HepG2细胞中WT1蛋白水平的表达,测定基因沉默效果;用MTT法测定HepG2细胞生长曲线;电镜下观察细胞凋亡形态,流式细胞仪检测凋亡率。结果:利用脂质体为载体将siRNA真核表达载体转染HepG2细胞,转染率达70%以上,转染后细胞中WT1蛋白表达水平下降;RNA干扰沉默WT1基因可抑制细胞增殖,促进细胞凋亡。结论:靶向WT1的序列特异性siRNA可显著抑制WT1基因的表达;下调HepG2细胞WT1基因表达可抑制细胞增殖,促进细胞凋亡。  相似文献   

11.
Renal dysplasia and asplenia in two sibs   总被引:2,自引:0,他引:2  
A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.  相似文献   

12.
Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc2 (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.  相似文献   

13.
About 1900, modern food selection and processing caused widespread epidemics of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a panhypovitaminosis B, i.e., a mixture of substrate beriberi and substrate pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse endemic disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for primates. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.  相似文献   

14.
15.
There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.  相似文献   

16.
Newton H 《Medical history》2011,55(2):153-182
Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.  相似文献   

17.
Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.  相似文献   

18.
The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.  相似文献   

19.
HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.  相似文献   

20.
There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.  相似文献   

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