河北省部分地区人巨细胞病毒激活感染的流行病学调查
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摘要
目的:自从Fabricant等以Marek病毒(一种禽类病毒)感染鸡而引起动脉粥样硬化以来,动脉粥样硬化的病毒病因学说受到越来越多学者的关注,人巨细胞病毒(Humancytomegalovirus,HCMV)被认为是与动脉粥样硬化关系最密切的一种病毒。本课题组的研究结果已证明临床HCMV的激活感染是动脉粥样硬化的独立危险因素之一,关于这一课题,国内外的许多学者从不同的角度进行了相关研究,有关HCMV感染与动脉粥样硬化间关系的实验室研究已有大量文献报道,但研究结果仍存在争议,而且实验室环境不能准确反映暴露于外部世界的真实条件,而流行病学则通过直接研究自然环境下的人群而避免了这类问题,实验室研究同流行病学调查的结合将对这一课题从不同的角度进行探讨。现有的流行病学资料多集中于孕妇、新生儿、献血员、器官移植者及免疫缺陷者(如多发性硬化、AIDS患者等),调查人群层面单一,不能反映整体人群HCMV的感染状况。HCMV-pp65是一种重要的晚期抗原,HCMV活动性感染时HCMV-pp65表达于外周血单核细胞、中性多形核白细胞和血管内皮细胞中,而潜伏感染时表达极低,现已成为国际公认的诊断HCMV活动性感染的标准方法之一。我们将在河北省11个行政区域内进行相关的流行病学调查,检测HCMV-pp65,并随访调查人群,进行前瞻性研究,观察其动脉粥样硬化性疾病尤其是脑梗死的发生情况,从流行病学角度探讨动脉粥样硬化与HCMV的关系,进一步探讨动脉粥样硬化的病因及相关危险因素,进而寻找防治缺血性脑血管病的新模式,这也是我们进行此次流行病学调查的主要目的。
方法:本研究采用免疫组织化学方法检测静脉血白细胞中的巨细胞病毒晚期抗原pp65,对河北省部分地区(包括石家庄市、藁城市、柳辛庄、赵县、高阳、蠡县、阜平、献县、赞皇、南皮、涉县、武邑、崇礼)人群巨细胞病毒的激活感染HCMV-pp65阳性率进行了流行病学调查,共1954例,其中男性781例,女性1173例,平均年龄(55.16±10.30)岁。各县、市按行政地域分成六个地区:石家庄地区、保定地区、沧州地区、邯郸地区、张家口地区和衡水地区。
利用microsoft excel建立数据库,将数据库资料导入为SAS数据集,利用SAS 6.12统计软件对所调查人群HCMV-pp65阳性率及其与地域、年龄、性别等相关因素进行统计学分析。计数资料采用x~2检验或校正的x~2检验,α=0.05。
结果:1对河北省13个县区的1954例调查对象抽取静脉血检测人巨细胞病毒晚期抗原pp65,免疫组化染色后,阴性细胞为均匀一致的蓝紫色,阳性细胞胞浆和(或)胞核为棕黄色,阳性细胞数大于1/50000判为pp65抗原阳性。
2河北省部分地区人群抽血检测人巨细胞病毒晚期抗原pp65,共1954例,其中农村1807例,城镇147例,平均年龄(55.16±10.30)岁,计算得出pp65阳性率17.14%。总体人群pp65阳性率在性别间差异无统计学意义,x~2=0.283,P＞0.05;年龄分组pp65阳性率差异有统计学意义,x~2=8.688,P＜0.05,以60-年龄组最高(20.74%),40-年龄组最低(14.11%);地区间pp65阳性率差异有统计学意义,x~2=55.246,P＜0.05,以保定地区最高(26.65%),依次为沧州(23.32%)、邯郸(22.22%)、张家口(19.57%)、衡水(11.95%)、石家庄(11.49%)。
3农村人群组1807例,平均年龄(55.87±10.19)岁,计算得出外周血pp65阳性率18.04%。农村人群pp65阳性率在性别间差异无统计学意义,x~2=1.948,P＞0.05;年龄分组pp65阳性率差异无统计学意义,x~2=6.824,P＞0.05;地区间pp65阳性率差异有统计学意义,x~2=44.386,P＜0.05,以保定地区最高(26.65%),依次为沧州(23.32%)、邯郸(22.22%)、张家口(19.57%)、石家庄(12.52%)、衡水(11.95%)。
4城镇人群组147例,平均年龄(46.87±7.54)岁,计算得出外周血pp65阳性率6.12%。城镇人群pp65阳性率在性别间差异无统计学意义,x~2=0.035,P＞0.05;年龄分组pp65阳性率差异无统计学意义,x~2=1.624,P＞0.05。
5农村与城镇人群外周血pp65阳性率比较差异有统计学意义,x~2=13.594,P＜0.05。
6平原地区与山区人群外周血pp65阳性率比较差异无统计学意义,x~2=2.396,P＞0.05。
结论:1河北省部分地区调查人群中HCMV-pp65阳性率为17.14%,说明普通人群中存在HCMV的激活感染;
2河北省各地区间存在HCMV-pp65阳性率的显著性差异;
3 HCMV-pp65阳性率性别间差异无统计学意义,但男性略高于女性;
4总体人群年龄分组HCMV-pp65阳性率区组间差异有统计学意义,而农村组和城镇组年龄分组差异均无统计学意义,但随年龄增加HCMV-pp65阳性率有上升趋势;
5农村与城镇人群HCMV-pp65阳性率比较差异有统计学意义,农村明显高于城镇;
6平原地区和山区HCMV-pp65阳性率无显著性差异;
7由研究结果推测所调查地区总体健康人群中HCMV的激活感染率应低于17.14%。
Objective:Increasing attention is being paid to the viral etiology of atherosclerosis(AS)for more and more scholars Since Fabricant inoculated Marekvirus to turkey and made it provoke atherosclerosis,and Human cytomegalovirus(HCMV) is thought to be the most possible etiological factor of atherosclerosis.We have proved that the active infection of HCMV was one of the risk factors of atherosclerosis in our previous study.Domestic and foreign scholars have been studying the topic in different aspects.There are many reports about the relationship between HCMV and atherosclerosis,but the findings are still in controversy.The surrounding of laboratory can not reflect the actual conditions exposed externally,while epidemiology avoids the shortcoming by studying the men exposed physical environment.The combination between laboratorial study and epidemiology will proof the topic in different directions.The present epidemiological datas are concentrated mostly in pregnant women,newborn infants,blood donors,organ transplanting receptors,immunologic deficitors(as multiple sclerosis,AIDS and so on),which can not reflect the infecting state in the whole crowds.HCMV-pp65 is a favourable late antigen which can express in peripheral blood monouclear cells,nertrophile polymorphonuclear leucocytes,vascular endothelial cells when HCMV is in reactiveness while can not be detected when in latent state.Detecting HCMV-pp65 has been one of the achnowledged internationally standard methods of diagnosing HCMV infection in reactiveness.We will carry out epidemiological survey about HCMV-pp65 in 11 administrative areas of Hebei Province,return to visit the surveying crowds,carry out prospective study,observe the occurrence of diseases related with atherosclerosis especially cerebral infarction.We will investigate the relationship between HCMV and atherosclerosis on epidemiology,research furtherly the etiological factors and risk factors of atherosclerosis so that we can go in search of the novel mode of preventing and curing ischemic cerebrovascular disease, which is the major purpose of the epidemiological survey.
Method:The immunohistochemical method was applied to detect cytomegaloviral late-antigen pp65 in leucocyte of peripheral blood.The article analyzed the epidemiological survey of the positive rate of HCMV-pp65 in crowds in several territories of Hebei province(Shijiazhuang,Gaocheng, Liuxinzhuang,Zhaoxian,Gaoyang,Lixian,Fuping,Xianxian, Zanhuang,Nanpi,Shexian,Wuyi,Chongli).The total number of surveying group was 1954 consisted of 781 men and 1173 women,the mean age was(55.16±10.03)years old.All of the surveying counties or cities were divided to 6 administrative areas:Shijiazhuang territory,Baoding Territory,Cangzhou territory,Handan territory,Zhangjiakou territory and Hengshui territory.
Make data pool by microsoft excel,import the data pool into SAS data set,analyze the positive rate of HCMV-pp65 about territory,age,sex and so on by SAS 6.12 statistical software.Numeral data by x~2 test or corrected x~2 test,α=0.05.
Results:1 The immunohistochemical method was applied to detect cytomegaloviral late-antigen pp65 in leucocyte of peripheral blood from 1954 samples.Negative cells were in uniform violet while the kytoplasm and(or)nucleus of positive cells were in brown.The positive conclusion should be made if positive cells exceeded 1/50000.
2 The immunohistochemical method was applied to detect HCMV-pp65 in leucocyte of peripheral blood from 1954 samples included 1807 from countryside and 147 from town, the mean age was(55.16±10.03)years old.The total positive rate of HCMV-pp65 was 17.14%in global crowds.There was no statistical difference about the positive rate of HCMV-pp65 on sexes in global crowds,x~2=0.283,P＞0.05;There was statistical difference about the positive rate of HCMV-pp65 on ages in global crowds,x~2=8.688,P＜0.05,60-stage was the highest(20.74%)and 40-stage was the lowest(14.11%);There was statistical difference about the positive rate of HCMV-pp65 on territories in global crowds,x~2=55.246,P＜ 0.05,Baoding territory ranked highest(26.65%),followed by Cangzhou territory(23.32%),Handan territory(22.22%), Zhangjiakou(19.57%),Hengshui(11.95%)and Shijiazhuang (11.49%).
3 The positive rate of HCMV-pp65 was 18.04%in rural crowds included 1807 samples,the mean age was (55.87±10.19)years old.There was no statistical difference about the positive rate of HCMV-pp65 on sexes in rural crowds, x~2=1.948,P＞0.05.There was no statistical difference about the positive rate of HCMV-pp65 on ages in rural crowds,x~2= 6.824,P＞0.05.There was statistical difference about the positive rate of HCMV-pp65 on territories in rural crowds,x~2= 44.386,P＜0.05,Baoding territory ranked highest(26.65%), followed by Cangzhou territory(23.32%),Handan territory (22.22%),Zhangjiakou(19.57%),Shijiazhuang(12.52%)and Hengshui(11.95%).
4 The positive rate of HCMV-pp65 was 6.12%in urban crowds included 147 samples,the mean age was(46.87±7.54) years old.There was no statistical difference about the positive rate of HCMV-pp65 on sexes in urban crowds,x~2=0.035,P＞0.05.There was no statistical difference about the positive rate of HCMV-pp65 on ages in urban crowds,x~2=1.624,P＞0.05.
5 There was statistical difference about the positive rate of HCMV-pp65 between rural crowds and urban crowds,x~2= 13.594,P＜0.05.
6 There was no statistical difference about the positive rate of HCMV-pp65 in crowds between plain area and mountain area,x~2=2.396,P＞0.05.
Conclusions:1 The positive rate of HCMV-pp65 was 17.14%in several territory of Hebei Provence which indicated there was activated infection of HCMV in common crowds;
2 There was statistical difference about the positive rate of HCMV-pp65 among territories;
3 There was no statistical difference about the positive rate of HCMV-pp65 on sexes but the positive rate of HCMV-pp65 was higher slightly in male than female;
4 There was statistical difference about the positive rate of HCMV-pp65 on ages in global crowds while there was no statistical difference on ages in rural crowds and urban crowds but a rising trend with growing ages;
5 There was statistical difference about the positive rate of HCMV-pp65 between rural crowds and urban crowds then it was higher obviously in rural crowds than in urban crowds;
6 There was no statistical difference about the positive rate of HCMV-pp65 in crowds between plain area and mountain area.
7 It could be inferred the active rate of HCMV in immunocompetent crowds should be lower than 17.14%.
方法:本研究采用免疫组织化学方法检测静脉血白细胞中的巨细胞病毒晚期抗原pp65,对河北省部分地区(包括石家庄市、藁城市、柳辛庄、赵县、高阳、蠡县、阜平、献县、赞皇、南皮、涉县、武邑、崇礼)人群巨细胞病毒的激活感染HCMV-pp65阳性率进行了流行病学调查,共1954例,其中男性781例,女性1173例,平均年龄(55.16±10.30)岁。各县、市按行政地域分成六个地区:石家庄地区、保定地区、沧州地区、邯郸地区、张家口地区和衡水地区。
利用microsoft excel建立数据库,将数据库资料导入为SAS数据集,利用SAS 6.12统计软件对所调查人群HCMV-pp65阳性率及其与地域、年龄、性别等相关因素进行统计学分析。计数资料采用x~2检验或校正的x~2检验,α=0.05。
结果:1对河北省13个县区的1954例调查对象抽取静脉血检测人巨细胞病毒晚期抗原pp65,免疫组化染色后,阴性细胞为均匀一致的蓝紫色,阳性细胞胞浆和(或)胞核为棕黄色,阳性细胞数大于1/50000判为pp65抗原阳性。
2河北省部分地区人群抽血检测人巨细胞病毒晚期抗原pp65,共1954例,其中农村1807例,城镇147例,平均年龄(55.16±10.30)岁,计算得出pp65阳性率17.14%。总体人群pp65阳性率在性别间差异无统计学意义,x~2=0.283,P＞0.05;年龄分组pp65阳性率差异有统计学意义,x~2=8.688,P＜0.05,以60-年龄组最高(20.74%),40-年龄组最低(14.11%);地区间pp65阳性率差异有统计学意义,x~2=55.246,P＜0.05,以保定地区最高(26.65%),依次为沧州(23.32%)、邯郸(22.22%)、张家口(19.57%)、衡水(11.95%)、石家庄(11.49%)。
3农村人群组1807例,平均年龄(55.87±10.19)岁,计算得出外周血pp65阳性率18.04%。农村人群pp65阳性率在性别间差异无统计学意义,x~2=1.948,P＞0.05;年龄分组pp65阳性率差异无统计学意义,x~2=6.824,P＞0.05;地区间pp65阳性率差异有统计学意义,x~2=44.386,P＜0.05,以保定地区最高(26.65%),依次为沧州(23.32%)、邯郸(22.22%)、张家口(19.57%)、石家庄(12.52%)、衡水(11.95%)。
4城镇人群组147例,平均年龄(46.87±7.54)岁,计算得出外周血pp65阳性率6.12%。城镇人群pp65阳性率在性别间差异无统计学意义,x~2=0.035,P＞0.05;年龄分组pp65阳性率差异无统计学意义,x~2=1.624,P＞0.05。
5农村与城镇人群外周血pp65阳性率比较差异有统计学意义,x~2=13.594,P＜0.05。
6平原地区与山区人群外周血pp65阳性率比较差异无统计学意义,x~2=2.396,P＞0.05。
结论:1河北省部分地区调查人群中HCMV-pp65阳性率为17.14%,说明普通人群中存在HCMV的激活感染;
2河北省各地区间存在HCMV-pp65阳性率的显著性差异;
3 HCMV-pp65阳性率性别间差异无统计学意义,但男性略高于女性;
4总体人群年龄分组HCMV-pp65阳性率区组间差异有统计学意义,而农村组和城镇组年龄分组差异均无统计学意义,但随年龄增加HCMV-pp65阳性率有上升趋势;
5农村与城镇人群HCMV-pp65阳性率比较差异有统计学意义,农村明显高于城镇;
6平原地区和山区HCMV-pp65阳性率无显著性差异;
7由研究结果推测所调查地区总体健康人群中HCMV的激活感染率应低于17.14%。
Objective:Increasing attention is being paid to the viral etiology of atherosclerosis(AS)for more and more scholars Since Fabricant inoculated Marekvirus to turkey and made it provoke atherosclerosis,and Human cytomegalovirus(HCMV) is thought to be the most possible etiological factor of atherosclerosis.We have proved that the active infection of HCMV was one of the risk factors of atherosclerosis in our previous study.Domestic and foreign scholars have been studying the topic in different aspects.There are many reports about the relationship between HCMV and atherosclerosis,but the findings are still in controversy.The surrounding of laboratory can not reflect the actual conditions exposed externally,while epidemiology avoids the shortcoming by studying the men exposed physical environment.The combination between laboratorial study and epidemiology will proof the topic in different directions.The present epidemiological datas are concentrated mostly in pregnant women,newborn infants,blood donors,organ transplanting receptors,immunologic deficitors(as multiple sclerosis,AIDS and so on),which can not reflect the infecting state in the whole crowds.HCMV-pp65 is a favourable late antigen which can express in peripheral blood monouclear cells,nertrophile polymorphonuclear leucocytes,vascular endothelial cells when HCMV is in reactiveness while can not be detected when in latent state.Detecting HCMV-pp65 has been one of the achnowledged internationally standard methods of diagnosing HCMV infection in reactiveness.We will carry out epidemiological survey about HCMV-pp65 in 11 administrative areas of Hebei Province,return to visit the surveying crowds,carry out prospective study,observe the occurrence of diseases related with atherosclerosis especially cerebral infarction.We will investigate the relationship between HCMV and atherosclerosis on epidemiology,research furtherly the etiological factors and risk factors of atherosclerosis so that we can go in search of the novel mode of preventing and curing ischemic cerebrovascular disease, which is the major purpose of the epidemiological survey.
Method:The immunohistochemical method was applied to detect cytomegaloviral late-antigen pp65 in leucocyte of peripheral blood.The article analyzed the epidemiological survey of the positive rate of HCMV-pp65 in crowds in several territories of Hebei province(Shijiazhuang,Gaocheng, Liuxinzhuang,Zhaoxian,Gaoyang,Lixian,Fuping,Xianxian, Zanhuang,Nanpi,Shexian,Wuyi,Chongli).The total number of surveying group was 1954 consisted of 781 men and 1173 women,the mean age was(55.16±10.03)years old.All of the surveying counties or cities were divided to 6 administrative areas:Shijiazhuang territory,Baoding Territory,Cangzhou territory,Handan territory,Zhangjiakou territory and Hengshui territory.
Make data pool by microsoft excel,import the data pool into SAS data set,analyze the positive rate of HCMV-pp65 about territory,age,sex and so on by SAS 6.12 statistical software.Numeral data by x~2 test or corrected x~2 test,α=0.05.
Results:1 The immunohistochemical method was applied to detect cytomegaloviral late-antigen pp65 in leucocyte of peripheral blood from 1954 samples.Negative cells were in uniform violet while the kytoplasm and(or)nucleus of positive cells were in brown.The positive conclusion should be made if positive cells exceeded 1/50000.
2 The immunohistochemical method was applied to detect HCMV-pp65 in leucocyte of peripheral blood from 1954 samples included 1807 from countryside and 147 from town, the mean age was(55.16±10.03)years old.The total positive rate of HCMV-pp65 was 17.14%in global crowds.There was no statistical difference about the positive rate of HCMV-pp65 on sexes in global crowds,x~2=0.283,P＞0.05;There was statistical difference about the positive rate of HCMV-pp65 on ages in global crowds,x~2=8.688,P＜0.05,60-stage was the highest(20.74%)and 40-stage was the lowest(14.11%);There was statistical difference about the positive rate of HCMV-pp65 on territories in global crowds,x~2=55.246,P＜ 0.05,Baoding territory ranked highest(26.65%),followed by Cangzhou territory(23.32%),Handan territory(22.22%), Zhangjiakou(19.57%),Hengshui(11.95%)and Shijiazhuang (11.49%).
3 The positive rate of HCMV-pp65 was 18.04%in rural crowds included 1807 samples,the mean age was (55.87±10.19)years old.There was no statistical difference about the positive rate of HCMV-pp65 on sexes in rural crowds, x~2=1.948,P＞0.05.There was no statistical difference about the positive rate of HCMV-pp65 on ages in rural crowds,x~2= 6.824,P＞0.05.There was statistical difference about the positive rate of HCMV-pp65 on territories in rural crowds,x~2= 44.386,P＜0.05,Baoding territory ranked highest(26.65%), followed by Cangzhou territory(23.32%),Handan territory (22.22%),Zhangjiakou(19.57%),Shijiazhuang(12.52%)and Hengshui(11.95%).
4 The positive rate of HCMV-pp65 was 6.12%in urban crowds included 147 samples,the mean age was(46.87±7.54) years old.There was no statistical difference about the positive rate of HCMV-pp65 on sexes in urban crowds,x~2=0.035,P＞0.05.There was no statistical difference about the positive rate of HCMV-pp65 on ages in urban crowds,x~2=1.624,P＞0.05.
5 There was statistical difference about the positive rate of HCMV-pp65 between rural crowds and urban crowds,x~2= 13.594,P＜0.05.
6 There was no statistical difference about the positive rate of HCMV-pp65 in crowds between plain area and mountain area,x~2=2.396,P＞0.05.
Conclusions:1 The positive rate of HCMV-pp65 was 17.14%in several territory of Hebei Provence which indicated there was activated infection of HCMV in common crowds;
2 There was statistical difference about the positive rate of HCMV-pp65 among territories;
3 There was no statistical difference about the positive rate of HCMV-pp65 on sexes but the positive rate of HCMV-pp65 was higher slightly in male than female;
4 There was statistical difference about the positive rate of HCMV-pp65 on ages in global crowds while there was no statistical difference on ages in rural crowds and urban crowds but a rising trend with growing ages;
5 There was statistical difference about the positive rate of HCMV-pp65 between rural crowds and urban crowds then it was higher obviously in rural crowds than in urban crowds;
6 There was no statistical difference about the positive rate of HCMV-pp65 in crowds between plain area and mountain area.
7 It could be inferred the active rate of HCMV in immunocompetent crowds should be lower than 17.14%.
引文
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7 Emery VC. Cytomegalovirus and the aging population. Drugs Aging, 2001, 18, :927-933
8 Yoshiaki Yamagishi, Hiromi Miyagawa, Kazuko Wada, et al. CMV DNA detection in dried blood spots for diagnosing congenital CMV infection in Japan. Jorunal of Med Virology, 2006 78 :923-925
9 Gerna G, Baldanti F, Torsellini M, et al. Evaluation of cytomegalovirus DNA aemia versus pp65-antigenaemia cutoff for guiding preemptive therapy in transplant recipients: a randomized study. Antivir Ther, 2007, 12, :63-72
10 Kim CK, Song JH, Kim SM, et al. Clinical usefulness of human cytomegalovirus antigenemia assay after kidney transplantation. Transplantation, 2003, 75, :2151-2155
11 Holland CA, Ma Y, Moscicki B, et al. Seroprevalence and risk factors of hepatitis B, hepatitis C, and human cytomegalovirus among HIV-infected and high-risk uninfected adolescents: findings of the REACH Study Adolescent Medicine HIV/AIDS Research Network. Sex Transm Dis, 2000, 27, :296-303
12 Spano LC, Gatti J, Nascimento JP, et al. Prevalence of human cytomegalovirus infection in pregnant and non-pregnant women.J Infect,2004,48,:213-220
13 叶冬青,黄芬,胡兆平,等.合肥地区职业献血员巨细胞病毒感染状况调查.临床输血与检验,1999,1:7-9
14 马道新,于修平,薛付忠,等.山东省人巨细胞病毒感染的流行病学调查及其相关因素研究.山东大学学报(医学版),2005,43:574-577
15 朱见文,何俊瑛,高玉林,等.短暂性脑缺血发作患者中人巨细胞病毒-pp65抗原检测.临床荟萃,2006,21:340-341
16 何俊瑛,高玉林,王永祥,等.进展性卒中与稳定性卒中巨细胞病毒抗原血症检测的临床意义.脑与神经疾病杂志,2004,12:280-282
17 肖丹,刘颖祺,李丽云,等.对92例健康献血员巨细胞病毒感染的监测报告.中国公共卫生,1997,13:726
18 Abarca K,Vial PA,Zamorano J,et al.Seroprevalance of cytomegalovirus and toxoplasma gondii in healthy subjects under 30 years old in Santiago chile.Rev Med Chil,I997,125:531-538
19 Gratacap CB,Morand P,Dutertre N.Cytomegalovirus infection in pregnant women seroepidemiological prospective study in 1018 women in Isere.J Gynecol Obstet Biol Reprod Paris,1998,27:161-166
20 胡兆平,宋海波,冉玲,等.安徽省合肥地区献血员的血清流行病学调查.疾病控制杂志,1997,1:112-114
21 Mustakangas P,Sama S,Ammala P,et al.Human cytomegalovirus seroprevalence in three socioeconomically different urban areas during the first trimester:a population-based cohort study.Int J Epidemiol,2000,29,:587-591
1 The TH, van den Berg AP, Harmsen MC, et al. The cytomegalovirus antigenemia assay: a plea for stand ardization. Scand J Infect Dis Suppl, 1995, 99: 25-29
2 Fabricant CG, Krook L, Gillespie JH. Virus-induced cholesterol crystals. Science, 1973, 181, 566-567
3 Span A. The effect of cytomegalovirus infection on the adherence of polymorphonuclear lerkocytes to endothelial cells. Eur J Clin Invest, 1989, 19: 542
4 Etingin OR, Silverstein RL, Powell BB, et al. Identification of a monocyte receptor on herpesvirus infected endothelial cells. Proc Natl Acad Sci U S A, 1991, 88: 7200-7203
5 Wright JF, Kurosky A. An endothelial cell surface form of annexin II binds cytomegalovirus. Biochem Biophys Res Commun, 1994, 198: 983-989
6 Bodaghi B, Slobbe Van, Drunen ME. Entry of human cytomegalovirus into retinal pigment epithelial and endothelial cells by endocytosis. Invest Ophthalmol Vis Sci, 1999, 40: 2598-2607
7 Bentz GL, Jarquin Pardo M, Chan G, et al. Human cytomegalovirus (HCMV) infection of endothelial cells promotes naive monocyte extravasation and transfer of productive virus to enhance hematogenous dissemination of HCMV. J Virol, 2006, 80: 11539-11555
8 Knight DA, Briggs BR, BennettCR. Attenuation of cytomegalovirus induced endothelial intercellular adhesion molecule-1 mRNA/protein expression and T lymphocyte adhension by a 2'-O-methoxyethyl antisense oligonucleotide. Transplantation, 2000, 69: 417-426
9 Basta G, Lazzerini G, Massaro M, et al. Advanced glycation end products activate endothelium through signa transduction receptor RAGE:a mechanism for amplifiction of inflammatory responses. Circulation, 2002,105: 816-822
10 Bierhaus A, Schiekofer S, Schwaninger M, et al. Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB. Diabetes, 2001, 50: 2792-2808
11 Speir E. Cytomegalovirus gene regulation by reactive oxygen species. Agents in atherosclerosis. Ann N Y Acad Sci, 2000, 899: 363-374
12 Leinonen M, Saikku P. Evidence for infectious agents in cardiovascular disease and atherosclerosis. Lancet Infect Dis, 2002,2:11-17
13 Zhu J. Antibodies to HSP60 are associated with the presence and severity of coronary artery disease: evidence for an autoimmune component of atherogenesis. Circulation, 2001, 103: 1071-1075
14 Bason C. Interaction of antibodies against cytomegalovirus with heat shock protein 60 in pathogenesis of atherosclerosis. Lancet, 2003, 362: 1971-1977
15 Borland G, Cushley W. Positioning the immune system: unexpected roles for a6-integrins. Immunology, 2004, 111: 381-383
16 Lunardi C, Bason C, Corrocher R. Induction of endothelial cell damage by HCMV molecular mimicry. Trends Immunol, 2005, 26: 19-24
17 Kilmartin B, Reen D.J. HSP60 induces self-tolerance to repeated HSP60 stimulation and cross-tolerance to other proinflammatory stimuli. Eur. J. Immunol, 2004, 34: 2041-2051
18 Patrone M, Secchi M, Fiorina L, et al. Human cytomegalovirus UL130 protein promotes endothelial cell infection through a producer cell modification of the virion. J Virol, 2005, 79:8361-8373
19 Gerna GE, Percivalle, F. Human cytomegalovirus replicates abortively in polymorphonuclear leukocytes after transfer from infected endothelial cells via transient microfusion events. J. Virol, 2000, 74: 5629-5638
20 Hahn G, Revello MG, Patrone M, et al. Human cytomegalovirus UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. J Virol, 2004, 78: 10023-10033
21 Rue CA, Jarvis MA, Knoche AJ, et al. A cyclooxygenase-2 homologue encoded by rhesus cytomegalovirus is a determinant for endothelial cell tropism. J Virol, 2004, 78: 12529-12536
22 Rahbar A, Soderberg-Naucler C. Human cytomegalovirus infection of endothelial cells triggers platelet adhesion and aggregation.J Virol,2005,79:2211-2220
23 黄晨,张怀荣,王晓明,等.人巨细胞病毒感染对人脐静脉内皮细胞周期和凋亡的影响.中国临床康复,2005,9:56-58
2 Griffiths PD.Molecular biology and immunology of cytomegalovirus.Biochem J,1987,241:313
3 The TH,van den Berg AP,Harmsen MC,et al.The cytomegalovirus antigenemia assay:a plea for stand ardization.Scand J Infect Dis Suppl,1995,99:25-29
4 Voisard R,Krugers T,Reinhardt B,et al.HCMV-infection in a human arterial organ culture model:effects on cell proliferation and neointimal hyperplasia.BMC Microbiol,2007,7:68
5 Shen YH,Zhang L,Utama B,et al.Human cytomegalovirus inhibits Akt-mediated eNOS activation through upregulating PTEN(phosphatase and tensin homolog deleted on chromosome 10).Cardiovasc Res,2006,69,2:502-511
6 Fateh Moghadam S, Bocksch W, Wessely R, et al. Cytomegalovirus infection status predicts progression of heart-transplant vasculopathy. Transplantation, 2003, 76, :1470-1474
7 Emery VC. Cytomegalovirus and the aging population. Drugs Aging, 2001, 18, :927-933
8 Yoshiaki Yamagishi, Hiromi Miyagawa, Kazuko Wada, et al. CMV DNA detection in dried blood spots for diagnosing congenital CMV infection in Japan. Jorunal of Med Virology, 2006 78 :923-925
9 Gerna G, Baldanti F, Torsellini M, et al. Evaluation of cytomegalovirus DNA aemia versus pp65-antigenaemia cutoff for guiding preemptive therapy in transplant recipients: a randomized study. Antivir Ther, 2007, 12, :63-72
10 Kim CK, Song JH, Kim SM, et al. Clinical usefulness of human cytomegalovirus antigenemia assay after kidney transplantation. Transplantation, 2003, 75, :2151-2155
11 Holland CA, Ma Y, Moscicki B, et al. Seroprevalence and risk factors of hepatitis B, hepatitis C, and human cytomegalovirus among HIV-infected and high-risk uninfected adolescents: findings of the REACH Study Adolescent Medicine HIV/AIDS Research Network. Sex Transm Dis, 2000, 27, :296-303
12 Spano LC, Gatti J, Nascimento JP, et al. Prevalence of human cytomegalovirus infection in pregnant and non-pregnant women.J Infect,2004,48,:213-220
13 叶冬青,黄芬,胡兆平,等.合肥地区职业献血员巨细胞病毒感染状况调查.临床输血与检验,1999,1:7-9
14 马道新,于修平,薛付忠,等.山东省人巨细胞病毒感染的流行病学调查及其相关因素研究.山东大学学报(医学版),2005,43:574-577
15 朱见文,何俊瑛,高玉林,等.短暂性脑缺血发作患者中人巨细胞病毒-pp65抗原检测.临床荟萃,2006,21:340-341
16 何俊瑛,高玉林,王永祥,等.进展性卒中与稳定性卒中巨细胞病毒抗原血症检测的临床意义.脑与神经疾病杂志,2004,12:280-282
17 肖丹,刘颖祺,李丽云,等.对92例健康献血员巨细胞病毒感染的监测报告.中国公共卫生,1997,13:726
18 Abarca K,Vial PA,Zamorano J,et al.Seroprevalance of cytomegalovirus and toxoplasma gondii in healthy subjects under 30 years old in Santiago chile.Rev Med Chil,I997,125:531-538
19 Gratacap CB,Morand P,Dutertre N.Cytomegalovirus infection in pregnant women seroepidemiological prospective study in 1018 women in Isere.J Gynecol Obstet Biol Reprod Paris,1998,27:161-166
20 胡兆平,宋海波,冉玲,等.安徽省合肥地区献血员的血清流行病学调查.疾病控制杂志,1997,1:112-114
21 Mustakangas P,Sama S,Ammala P,et al.Human cytomegalovirus seroprevalence in three socioeconomically different urban areas during the first trimester:a population-based cohort study.Int J Epidemiol,2000,29,:587-591
1 The TH, van den Berg AP, Harmsen MC, et al. The cytomegalovirus antigenemia assay: a plea for stand ardization. Scand J Infect Dis Suppl, 1995, 99: 25-29
2 Fabricant CG, Krook L, Gillespie JH. Virus-induced cholesterol crystals. Science, 1973, 181, 566-567
3 Span A. The effect of cytomegalovirus infection on the adherence of polymorphonuclear lerkocytes to endothelial cells. Eur J Clin Invest, 1989, 19: 542
4 Etingin OR, Silverstein RL, Powell BB, et al. Identification of a monocyte receptor on herpesvirus infected endothelial cells. Proc Natl Acad Sci U S A, 1991, 88: 7200-7203
5 Wright JF, Kurosky A. An endothelial cell surface form of annexin II binds cytomegalovirus. Biochem Biophys Res Commun, 1994, 198: 983-989
6 Bodaghi B, Slobbe Van, Drunen ME. Entry of human cytomegalovirus into retinal pigment epithelial and endothelial cells by endocytosis. Invest Ophthalmol Vis Sci, 1999, 40: 2598-2607
7 Bentz GL, Jarquin Pardo M, Chan G, et al. Human cytomegalovirus (HCMV) infection of endothelial cells promotes naive monocyte extravasation and transfer of productive virus to enhance hematogenous dissemination of HCMV. J Virol, 2006, 80: 11539-11555
8 Knight DA, Briggs BR, BennettCR. Attenuation of cytomegalovirus induced endothelial intercellular adhesion molecule-1 mRNA/protein expression and T lymphocyte adhension by a 2'-O-methoxyethyl antisense oligonucleotide. Transplantation, 2000, 69: 417-426
9 Basta G, Lazzerini G, Massaro M, et al. Advanced glycation end products activate endothelium through signa transduction receptor RAGE:a mechanism for amplifiction of inflammatory responses. Circulation, 2002,105: 816-822
10 Bierhaus A, Schiekofer S, Schwaninger M, et al. Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB. Diabetes, 2001, 50: 2792-2808
11 Speir E. Cytomegalovirus gene regulation by reactive oxygen species. Agents in atherosclerosis. Ann N Y Acad Sci, 2000, 899: 363-374
12 Leinonen M, Saikku P. Evidence for infectious agents in cardiovascular disease and atherosclerosis. Lancet Infect Dis, 2002,2:11-17
13 Zhu J. Antibodies to HSP60 are associated with the presence and severity of coronary artery disease: evidence for an autoimmune component of atherogenesis. Circulation, 2001, 103: 1071-1075
14 Bason C. Interaction of antibodies against cytomegalovirus with heat shock protein 60 in pathogenesis of atherosclerosis. Lancet, 2003, 362: 1971-1977
15 Borland G, Cushley W. Positioning the immune system: unexpected roles for a6-integrins. Immunology, 2004, 111: 381-383
16 Lunardi C, Bason C, Corrocher R. Induction of endothelial cell damage by HCMV molecular mimicry. Trends Immunol, 2005, 26: 19-24
17 Kilmartin B, Reen D.J. HSP60 induces self-tolerance to repeated HSP60 stimulation and cross-tolerance to other proinflammatory stimuli. Eur. J. Immunol, 2004, 34: 2041-2051
18 Patrone M, Secchi M, Fiorina L, et al. Human cytomegalovirus UL130 protein promotes endothelial cell infection through a producer cell modification of the virion. J Virol, 2005, 79:8361-8373
19 Gerna GE, Percivalle, F. Human cytomegalovirus replicates abortively in polymorphonuclear leukocytes after transfer from infected endothelial cells via transient microfusion events. J. Virol, 2000, 74: 5629-5638
20 Hahn G, Revello MG, Patrone M, et al. Human cytomegalovirus UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. J Virol, 2004, 78: 10023-10033
21 Rue CA, Jarvis MA, Knoche AJ, et al. A cyclooxygenase-2 homologue encoded by rhesus cytomegalovirus is a determinant for endothelial cell tropism. J Virol, 2004, 78: 12529-12536
22 Rahbar A, Soderberg-Naucler C. Human cytomegalovirus infection of endothelial cells triggers platelet adhesion and aggregation.J Virol,2005,79:2211-2220
23 黄晨,张怀荣,王晓明,等.人巨细胞病毒感染对人脐静脉内皮细胞周期和凋亡的影响.中国临床康复,2005,9:56-58