大肠癌中Beclin1、LC3和mTOR的表达及意义

目的：探讨Beclin1、LC3和mTOR在大肠癌中的表达及意义。方法采用免疫组化EnVision法、Western blot和RT-PCR技术检测Beclin1、LC3和mTOR在大肠癌中的表达,并结合临床病理因素进行分析。结果 Beclin1、LC3和mTOR在大肠癌中的阳性率分别为90．50%、87．19%和46．28%,均明显高于癌旁组织( P<0．05),且LC3蛋白在中+低分化大肠癌中的表达(91．34%、89．58%)高于高分化大肠癌(77．61%),在有淋巴结转移组的表达(95．41%)高于无淋巴结转移组(80．45%), mTOR在有淋巴结转移组的表达(57．80%)高于无淋巴结转移组(35．33%)(P<0．05),Beclin1过表达与大肠癌分化程度和淋巴结转移均无关(P>0．05)。 LC3与Beclin1在大肠癌中表达呈正相关(rs =0．593,P<0．01),与mTOR表达呈负相关(rs =-0．165,P<0．01),Beclin1和mTOR表达之间无明显相关性(P>0．05)。 Kaplan-Meier生存分析显示,Beclin1和LC3均阳性、mTOR阴性、无淋巴结转移的大肠癌患者5年生存率高于Beclin1和LC3均阴性、mTOR阳性及有淋巴结转移的患者。多因素分析显示,LC3、mTOR和淋巴结转移是影响大肠癌预后的独立因素。 RT-PCR和Western blot检测结果显示：Beclin1、LC3和mTOR mRNA和蛋白表达水平均明显高于癌旁组织(P<0．05)。结论自噬相关基因Beclin1、LC3和mTOR的异常表达可能与大肠癌的发生、发展及预后相关;联合检测Beclin1、LC3和mTOR在大肠癌中的表达有助于评估进展程度和预后判断。     

食管鳞状细胞癌中Beclin1、LC3和mTOR的表达及其临床意义

目的探讨Beclin1、LC3和m TOR在食管鳞状细胞癌中的表达,并分析其临床意义。方法采用免疫组化En Vision法检测食管30例正常黏膜、32例低级别上皮内瘤变、34例高级别上皮内瘤变、35例早期癌及126例进展期癌中Beclin1、LC3和m TOR的表达,并分析其相关性及其与临床病理特征的关系。结果 Beclin1在进展期癌组中的表达高于其他四组(P0.005)。LC3在食管进展期癌组的表达高于正常黏膜组、低级别上皮内瘤变及早期癌组(P0.005)。m TOR在进展期癌组中的表达高于正常黏膜组、低级别上皮内瘤变及高级别上皮内瘤变组(P0.005)。Beclin1、LC3、m TOR表达与肿瘤TNM分期、淋巴结转移具有显著相关性(P0.05)。Beclin1与LC3、Beclin1与m TOR在食管进展期癌中的表达均呈正相关(P0.05),m TOR与LC3在高级别上皮内瘤变组及进展期癌中的表达呈正相关(P0.05)。结论在食管癌的发生、发展中,Beclin1作为抑癌基因激活自噬,导致肿瘤细胞过度自我消耗死亡;m TOR通过抑制自噬及促进血管生成,促进肿瘤生长。联合检测Beclin1、LC3和m TOR在食管癌中的表达,有助于评估进展程度和预后判断。     

Beclin 1、LC3-II及P62蛋白在上皮性卵巢癌中的表达及意义

目的探讨上皮性卵巢癌中Beclin、LC3-Ⅱ及P62蛋白的表达及临床意义。方法选取2011年6月—2013年3月我院手术切除并经病理学检查确诊的上皮性卵巢癌标本50例为实验组,同期手术切除正常卵巢组织20例作为对照,通过免疫组织化学sP法,检测标本中Beclin1、LC3．Ⅱ及P62蛋白的表达情况,并结合临床病理资料进行分析。结果在上皮性卵巢癌组织中,Beclin 1、LC3-Ⅱ蛋白的阳性表达率分别为46．00％（23／50）和42．00％（21／50）,低于正常卵巢组织的95．00％（19／20）和85．00％（17／20）;而P62蛋白的阳性表达率为72．00％（36／50）,高于正常卵巢组织的10．00％（2／20）,差异均具有统计学意义（P值均〈0．05）。在上皮性卵巢癌组织中,Beclin1、LC3-Ⅱ蛋白的表达与FIGO分期、病理分级具有相关性（P〈0．05）,而P62蛋白的表达与FIGO分期具有相关性（P〈0．05）。Beclinl蛋白和LC3-Ⅱ蛋白在上皮性卵巢癌组织中的表达呈正相关（P〈0．01）,P62蛋白的表达与Beclin1、LC3-Ⅱ蛋白均呈负相关（P〈0．01）。结论在上皮性卵巢癌组织中,Beclin1、LC3-Ⅱ和P62蛋白的异常表达,可导致自噬体形成减少和自噬功能减弱;可能与卵巢癌的发生、发展和预后不良有关。     

自噬相关基因Beclin1和LC3在卵巢浆液性癌中的表达及临床意义

目的检测Beclin1和LC3在卵巢浆液性癌(ovarian serous carcinoma,OSC)中的表达,探讨两者与OSC临床病理特征及预后的关系。方法采用免疫组化Max Vision两步法检测63例OSC和20卵巢浆液性囊腺瘤组织中Beclin1和LC3蛋白的表达,分析两者与OSC临床病理特征及预后的关系。应用RT-PCR和Western blot法检测10例新鲜OSC组织和相应癌旁组织中Beclin1和LC3 mRNA和蛋白的表达。结果在OSC组织中Beclin1和LC3蛋白阳性率(36.51%、33.33%)均低于卵巢浆液性囊腺瘤组织(65.00%、60.00%),差异有统计学意义(P=0.025,P=0.034)。Beclin1蛋白表达与临床FIGO分期和病理分级有关(P=0.001,P=0.001),与患者年龄、发病部位、肿瘤大小及有无盆腔淋巴结转移无关(P0.05)。LC3蛋白表达与临床FIGO分期和盆腔淋巴结转移有关(P=0.013,P=0.041),与患者年龄、发病部位、肿瘤大小和病理分级均无关(P0.05)。Beclin1和LC3在OSC中的表达呈显著正相关(r_s=0.373,P=0.03)。10例新鲜OSC组织中Beclin1和LC3 mRNA的相对表达量(0.581±0.091、0.650±0.090)低于癌旁组织,两者比较差异有统计学意义(t=8.083,t=6.614;P=0.016,P=0.022)。新鲜OSC组织中Beclin1和LC3蛋白的相对表达量明显低于癌旁组织,两者比较差异有统计学意义(P0.05)。Kaplan-Meier生存分析表明,Beclin1和LC3表达与OSC患者预后相关(P=0.028 3,P=0.018 5)。结论自噬相关基因Beclin1和LC3在OSC组织中的表达下降,导致自噬功能减弱,可能与OSC的发生、发展和预后不良相关。     

TNF-α诱导B16细胞自体吞噬的作用研究

目的 研究肿瘤坏死因子a(TNF-a)诱导小鼠黑色素瘤B16细胞自体吞噬和自噬性死亡的作用.方法体外培养小鼠黑色素瘤B16细胞,TN F-a(20ng/ml)处理后不同时间点(12、24h)分别收取细胞,相差显微镜观察TNF-α处理前后B16细胞的生存状态,透射电子显微镜(TEM)观察TNF-a处理前后B16细胞内双层膜结构自体吞噬泡的情况,反转录聚合酶链式反应(RT-PCR)、蛋白免疫印迹分析自噬标记物微管相关蛋白1轻链3(LC3]和Beclin1以及自噬相关基因(Atg)Atg5、Atg7、Atg12表达的变化,以LC3-Ⅱ/LC3-Ⅰ的比值作为自噬活性的指标,以Beclin1作为自噬性死亡的指标.结果TNF-a处理B16细胞24 h后自体吞噬泡数量增多.与对照组相比,TNF-α持续作用可以诱导自噬标记物LC3-Ⅱ和自噬性死亡标记物Beclin1蛋白表达增高,并且呈时间依赖性;同时自噬相关基因Atg5、Atg7 、Atg12 mRNA的表达在TNF-a处理12、24h后显著增高.结论TNF-α除了可以诱导B16细胞凋亡,还可诱导B16细胞发生自体吞噬并导致自噬性死亡.     

Beclin 1、LC3-Ⅱ及P62蛋白在上皮性卵巢癌中的表达及意义

目的 探讨上皮性卵巢癌中Beclin 1、LC3-Ⅱ及P62蛋白的表达及临床意义。方法 选取2011年6月—2013年3月我院手术切除并经病理学检查确诊的上皮性卵巢癌标本50例为实验组,同期手术切除正常卵巢组织20例作为对照,通过免疫组织化学SP法,检测标本中Beclin 1、LC3-Ⅱ及P62蛋白的表达情况,并结合临床病理资料进行分析。结果 在上皮性卵巢癌组织中,Beclin 1、LC3-Ⅱ蛋白的阳性表达率分别为46.00%(23/50)和42.00%(21/50),低于正常卵巢组织的95.00%(19/20)和85.00%(17/20);而P62蛋白的阳性表达率为72.00%(36/50),高于正常卵巢组织的10.00%(2/20),差异均具有统计学意义(P值均＜0.05)。在上皮性卵巢癌组织中,Beclin 1、LC3-Ⅱ蛋白的表达与FIGO分期、病理分级具有相关性(P＜0.05),而P62蛋白的表达与FIGO分期具有相关性(P＜0.05)。Beclin 1蛋白和LC3-Ⅱ蛋白在上皮性卵巢癌组织中的表达呈正相关(P＜0.01),P62蛋白的表达与Beclin 1、LC3-Ⅱ蛋白均呈负相关(P＜0.01)。 结论 在上皮性卵巢癌组织中,Beclin 1、LC3-Ⅱ和P62蛋白的异常表达,可导致自噬体形成减少和自噬功能减弱;可能与卵巢癌的发生、发展和预后不良有关。     

地塞米松诱导的危重病性肌病大鼠骨骼肌Beclin1、LC3的表达

目的 　观察地塞米松对大鼠危重病性肌病（CIM）比目鱼肌细胞自噬相关因子Beclin1和LC3表达的影响,探讨地塞米松诱导的大鼠危重病性肌病的可能机制。 方法　将健康SD大鼠分为对照组和实验组;实验组又分为7,9,11d 3个时相点（n=10）。实验组采用5mg/kg地塞米松连续腹腔注射,每天1次,对照组腹腔注射等量的生理盐水。采用足迹法判定肌功能缺损情况。利用免疫组化和Western blot检测比目鱼肌细胞自噬相关因子Beclin1和LC3的表达情况。 结果　与对照组相比,实验组大鼠出现不同程度肌肉功能缺损症状,以11d时大鼠缺损程度最为严重。Western blot结果显示,对照组或可见微弱的Beclin1、LC3阳性表达,随着时间延长,实验组可见明显的Beclin1、LC3阳性表达,以11d时相点表达最为明显。免疫组化结果也证实了同一趋势。 结论　地塞米松诱导的大鼠CIM可能通过激活Beclin1和LC3的表达从而发挥对细胞自噬的调节作用。     

白藜芦醇对血清剥夺诱导大鼠皮层神经元自噬的影响

目的:研究白藜芦醇(RSV)对血清剥夺诱导大鼠神经元自噬的影响及分子机制。方法:将原代培养的大鼠皮层神经元分为对照组(control)、血清剥夺组(SD)、RSV处理组(RSV)和RSV联合组SIRT1抑制剂EX527处理组(RSV+EX 527),利用乳酸脱氢酶(LDH)检测试剂盒检测细胞活性,免疫荧光染色检测沉默信息调节因子2相关酶1(SIRT1)的表达变化、Western Blot检测自噬相关蛋白LC3和Beclin1的表达水平变化。结果:与正常对照组相比,血清剥夺引起细胞活性下降、SIRT1表达下降,LC3-Ⅱ/LC3-Ⅰ比例减少,Beclin1表达降低(P 0. 05);经过RSV处理后,细胞活性增加(P 0. 05),大鼠神经元SIRT1表达增加,LC3-Ⅱ/LC3-Ⅰ比例增加,Beclin1表达增加;使用EX 527处理后,RSV的神经保护作用受到抑制。结论:RSV通过激活SIRT1活性促进大鼠皮层神经元自噬。     

食管鳞状细胞癌中Beclin1表达及其对增殖的影响

目的探讨Beclin1在食管鳞状细胞癌(esophagus squamous cell carcinoma,ESCC)中的表达及意义,分析其过表达对人ESCC细胞株TE1体外生长活性的影响。方法分别采用免疫组化SP法和RT-PCR技术检测57例ESCC及癌旁正常食管黏膜组织中Beclin1蛋白及mRNA的表达;利用基因转染、RT-PCR及Western blot法观察外源性Beclin1过表达对ESCC细胞株TE1的影响;MTT法分析外源性Beclin1过表达对TE1细胞增殖的影响;流式细胞仪(flow cytometry,FCM)检测转染后肿瘤细胞的细胞周期和凋亡;在荧光显微镜下观察转染后肿瘤细胞的自噬。结果免疫组化染色结果示,在ESCC中Beclin1蛋白的阳性率为29.82%(17/57),明显低于癌旁正常食管黏膜组织100%(57/57)(P<0.00),Beclin1蛋白的表达与ESCC患者的分化程度(χ2=6.158,P=0.046)、淋巴结转移(χ2=5.664,P=0.017)有关;与患者性别、年龄、肿瘤大小、浸润深度无关;RT-PCR检测结果示,在ESCC中Beclin1 mRNA的表达量(0.168±0.038)明显低于癌旁正常食管黏膜组织(0.280±0.052)(P<0.00)。pCMV6-Entry-Beclin1脂质体法转染TE1细胞后,在mRNA和蛋白水平Beclin1的表达均高于TE1PE组及TE1组。在TE1细胞中过表达Beclin1后可抑制肿瘤细胞的体外生长,抑制率为57.21%。FCM检测pCMV6-Entry-Beclin1转染后G1期细胞明显增多,S期细胞明显减少,细胞增殖受到抑制;凋亡率为5.91%,高于TE1PE组和TE1组(P<0.05)。在荧光显微镜下见TE1Beclin1组中MDC标记的自噬囊泡数量明显增加。结论自噬相关基因Beclin1 mRNA及蛋白在ESCC中表达下调,自噬活性的降低可能与ESCC的发生、发展及侵袭转移有关;Beclin1过表达可抑制人ESCC细胞株TE1的增殖,并诱导其自噬和凋亡,利用自噬基因Beclin1对ESCC基因治疗也许具有可行性。     

口腔癌患者中 SOX9、 Beclin1 的表达与预后转归的关系

目的 探讨口腔癌患者中性别决定基因盒 9 ( sex-determining region Y box 9, SOX9)、 自噬基因 (Beclin1) 的表达与预后转归的关系。 方法 选取 2017 年 5 月至 2018 年 5 月河北省保定市第一中心医院口 腔科收治的 38 例口腔癌患者, 取其口腔癌组织标本 38 份和癌旁组织标本 30 份, 检测患者口腔癌组织中 SOX9、 Beclin1 的表达情况。 分析 SOX9、 Beclin1 阳性表达与临床病理因素的关系, 采用 COX 分析影响口腔 癌预后转归的危险因素, 分析 SOX9、 Beclin1 与预后转归的关系。 结果 口腔癌组织中 SOX9 和 Beclin1 阳 性表达率显著高于癌旁正常组织 (P< 0. 05), SOX9、 Beclin1 阳性表达与年龄、 性别无关 (P > 0. 05), 与 肿瘤分期、 分化程度和淋巴转移相关 (P< 0. 05)。 对口腔癌预后影响因素采取 Cox 逐步回归分析, 结果显 示肿瘤分期、 淋巴转移、 SOX9、 Beclin1 是影响口腔癌患者预后转归的独立危险因素 (P< 0. 05)。 SOX9 阳 性及阴性表达患者无进展生存期分别为 10 ~ 18 月 [平均 (12. 5 ± 2. 4) 月]、 14 ~ 23 月 [平均 (17. 5 ± 3. 1) 月]; Beclin1 阳性及阴性表达患者无进展生存期分别为 11 ~ 18 月 [平均 (13. 7 ± 2. 4) 月]、 13 ~ 22 月 [平均 (15. 7 ± 3. 1) 月]。 SOX9、 Beclin1 阳性表达患者无进展生存期显著低于阴性表达患者 (c²=7.969、3.315,P＜0.05）。结论 口腔癌患者中 SOX9、 Beclin1 呈阳性表达, 其表达与预后转归密切相关, 口腔癌患者 SOX9、 Beclin1 表达越高预后转归越差。     

先兆子痫患者HLA-DQA1、-DQB、-DPA1基因多态性

目的：探讨人类白细胞抗原HLA-DQA1、-DQB1、-DPA1基因多态性与先兆子痫发病的关系。方法：采用序列特异性引物技术（PCR-SSP） 对46例先兆子痫患者和105例正常孕妇及其新生儿进行HLA-DQ-DPA1等位基因分型。结果：所有标本共检出11种HLA-DQA1基因表型、16种HLA-DQB1基因表型、6种HLA-DPA1基因表型。先兆子痫患者HLA-DQB1＊0301基因频率高于正常孕妇，差异有显著性（Pc=0．032，RR=2．43，AR=0．30），其余各基因表型频率两组比较差异均无显著性。结论：HLA-DQB1＊0301基因可能是一种先兆子痫发病的易感基因。     

Comprehensive sequence analysis of HLA-DQA1 and -DQB1 alleles and characterization of DRB1-QAP-DQA1-DQB1 haplotypes

It is well known that both chain and β chain of HLA-DQ are highly polymorphic. However the polymorphisms outside the hypervariable region were not fully examined so far. To further clarify the polymorphisms in DQ genes, we determined the nucleotide sequences of full length cDNA, spanning from the leader sequence to the stop codon, from 15 DQA1 alleles and 15 DQB1 alleles. We identified several new DQ alleles which had identical exon 2 sequence and were different in other exons. On the basis of the sequence analyses, a comprehensive PCR-based oligotyping system for DQA1 gene was established. We then characterized DRB1-QAP(DQA1 promoter)-DQA1-DQB1 haplotypes of B-lymphoblastoid cell lines homozygous for HLA and healthy unrelated Japanese and Norwegian populations. It was revealed that DQA1 alleles, which were identical in exon 2 but different in other exons, showed close linkage disequilibrium with diferent characteristic DRB1, QAP and DQB1 alleles. These results suggest that DR-DQ haplotypes have been generated in the early stage of molecular evolution.     

HLA-DRB1, -DQA1, -DQB1 and DPB1 susceptibility alleles in Cameroonian type 1 diabetes patients and controls

It is known that certain combinations of alleles within the human leucocyte antigen (HLA) complex are associated with susceptibility or resistance to type 1 diabetes. Variable associations of DR and DQ with type 1 diabetes are documented in Caucasians but rarely in African populations; however, the role of HLA-DP genes in type 1 diabetes remains uncertain. In order to investigate the HLA class II associations with type 1 diabetes in Cameroonians, we used sequence-specific oligonucleotide probing (SSOP) to identify DRB1, DQA1, DQB1 and DPB1 alleles in 10 unrelated C-peptide negative patients with type 1 diabetes and 90 controls from a homogeneous population of rural Cameroon. We found a significantly higher frequency of the alleles DRB1*03 (χ² = 17.9; P = 0.001), DRB1*1301 (χ² = 37.4; P < 0.0001), DQA1*0301 (χ² = 18.5; P = 0.001) and DQB1*0201 (χ² = 37.4; P < 0.001) in diabetes patients compared to the control group. The most frequent alleles in the control population were DQA1*01, DQB1*0602 and DRB1*15. The DRB1*04 allele was not significantly associated with type I diabetes in our study population. We observed no significant difference between patients and controls in DPB1 allele frequency. In conclusion, the data in Cameroonian diabetes patients suggest the existence of HLA class II predisposing and specific protective markers, but do not support previous reports of a primary association between HLA-DP polymorphism and development of type I diabetes .     

先兆子痫患者HLA-DQA1、-DQB1、-DPA1基因多态性

目的:探讨人类白细胞抗原HLA-DQ-A1、DQB1、DPA1基因多态性与先兆子痫发病的关系。方法:采用序列特异性引物技术(PCRSSP)对46例先兆子痫患者和105例正常孕妇及其新生儿进行HLA-DQ-DPA1等位基因分型。结果:所有标本共检出11种HLADQA1基因表型、16种HLADQB1基因表型、6种HLADPA1基因表型。先兆子痫患者HLA-DQ-B10301基因频率高于正常孕妇,差异有显著性(Pc=0.032,RR=2.43,AR=0.30),其余各基因表型频率两组比较差异均无显著性。结论:HLADQB10301基因可能是一种先兆子痫发病的易感基因。     

Allelism between pso1-1 and rev3-1 mutants and between pso2-1 and snm1 mutants in Saccharomyces cerevisiaee

Summary In the yeast Saccharomyces cerevisiae, allelism between the psol-1 and the rev3-1 mutants on the one hand and the pso2-1 and snm1 mutants on the other, is demonstrated by the comparison of phenotypes, complementation tests and meiotic segregation analysis.     

Glutathione-s-transferase M1 and T1 polymorphisms and associations with type 1 diabetes age-at-onset

Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic beta cell destruction involving auto-reactive T-cells, pro-inflammatory cytokines, reactive oxygen species (ROS) and loss of insulin. Monozygotic twin studies show a 20–60% concordance with T1D indicating there may be an environmental component to the disease. Glutathione (GSH) is the major endogenous antioxidant produced by the cell. GSH participates directly in the neutralization of free radicals and plays a role in the immune response. Glutathione-s-transferases (GSTs) conjugate GSH to free-radicals or xenobiotics. GST activity depletes GSH levels and may either detoxify or enhance the toxicity of a compound. Glutathione-s-transferase mu 1 (GSTM1) and glutathione-s-transferase theta 1 (GSTT1) have polymorphic homozygous deletion (null) genotypes resulting in complete absence of enzyme activity. GSTM1 and GSTT1 null genotypes in Caucasian populations have frequencies of approximately 40–60% and 15–20%, respectively. GST null genotypes have been associated with susceptibility to cancer and protection against chronic pancreatitis. The aim of this study was to investigate associations with GSTM1 and GSTT1 polymorphisms in a group T1D patients and control subjects 0–35 years old who participated in the Combined Swedish Childhood Diabetes Registry and Diabetes Incidence Study (1986–1988). Results show that the presence of the GSTM1 and not the null genotype (OR, 2.13 95% CI, 1.23–3.70, p-value, 0.007, Bonferroni corrected p-value, 0.035) may be a susceptibility factor in T1D 14–20 years old. These results suggest that the GSTM1 null genotype is associated with T1D protection and T1D age-at-onset and that susceptibility to T1D may involve GST conjugation.     

Interleukin-1, Interleukin-1 Receptors and Interleukin-1 Receptor Antagonist

IL-1 (IL-1α or IL-1β) is the prototypic “multifunctional” cytokine. Unlike the lymphocyte and colony stimulating growth factors, IL-1 affects nearly every cell type, and often in concert with other cytokines or small mediator molecules. Although some lymphocyte and colony stimulating growth factors may be therapeutically useful, IL-1 is a highly inflammatory cytokine and the margin between clinical benefit and unacceptable toxicity in humans is exceedingly narrow. In contrast, agents that reduce the production and/or activity of IL-1 are likely to have an impact on clinical medicine. In support of this concept, there is growing evidence that the production and activity of IL-1, particularly IL-1β, are tightly regulated events as if nature has placed specific “road blocks” to reduce the response to IL-1 during disease. In addition to controlling gene expression, synthesis and secretion, this regulation extends to surface receptors, soluble receptors and a receptor antagonist. Investigators have studied how production of the different members of the IL-1 family is controlled, the various biological activities of IL-1, the distinct and various functions of the IL-1 receptor (IL-1R) family and the complexity of intracellular signaling. Mice deficient in IL-1β, IL-1β converting enzyme (ICE) and IL-1R type I have also been studied. Humans have been injected with IL-1 (either IL-1α or IL-1β) for enhancing bone marrow recovery and for cancer treatment. The IL-1 specific receptor antagonist (IL-IRa) has also been tested in clinical trials.     

Aspirin-induced asthma and HLA-DRB1 and HLA-DPB1 genotypes

Background Aspirin-induced asthma (AIA) affects one in 10 individuals with adult-onset asthma. It is not known if aspirin sensitivity is due to immune mechanisms or to interference with biochemical pathways. Objective The study aimed to test for possible involvement of the genes of the Major Histocompatibility Complex (MHC) in AIA. Methods HLA-DPB1 and HLA-DRB1 genotyping was carried out by DNA methods in 59 patients with positive challenge tests for AIA and in 48 normal and 57 asthmatic controls Results The DPB 1*0301 frequency was increased in AIA patients when compared with normal controls (19.5% vs 5.2%, Odds Ratio = 4.4, 95% Confidence Interval (CI) 1.6–12.1, P= 0.002), and compared with asthmatic controls (4.4%, OR = 5.3, 95%CI= 1.9–14.4, P= 0.0001). The frequency of DPB 1*0401 in AIA subjects was decreased when compared with normal controls (28.8% vs 49.0%, OR = 0.42, 95%CI = 0.24–0.74, P= 0.003) and asthmatic controls (45.6%, OR = 0.48, 95%CI = 0.28–0.83, P= 0.008). The results remained significant when corrected for multiple comparisons. There were no significant HLA-DRB 1 associations with AIA. Conclusion The presence of an HLA association suggests that immune recognition of an unknown antigen may be part of the aetiology of AIA.     

NDE1 and NDEL1: Multimerisation,alternate splicing and DISC1 interaction

Nuclear Distribution Factor E Homolog 1 (NDE1) and NDE-Like 1 (NDEL1) are highly homologous mammalian proteins. However, whereas NDEL1 is well studied, there is remarkably little known about NDE1. We demonstrate the presence of multiple isoforms of both NDE1 and NDEL1 in the brain, showing that NDE1 binds directly to multiple isoforms of Disrupted in Schizophrenia 1 (DISC1), and to itself. We also show that NDE1 can complex with NDEL1. Together these results predict a high degree of complexity of DISC1-mediated regulation of neuronal activity.     

AhR途径,CYP1A1、CYP1B1,雌激素代谢及作用过程中的调节

多环芳烃和多卤化烃是环境中广泛分布的有害物质,可通过与细胞芳烃受体结合,从而影响外来化合物代谢酶系如细胞色素氧化酶P450 1A1、1B1的表达,并通过这些酶的催化作用调控雌激素的代谢及作用,进而部分决定了雌激素对机体的作用效应。上述复杂的过程可受到多种因素的影响。