肿瘤坏死因子-α基因多态性与乙型肝炎病毒宫内感染易感性的关系

目的 探讨肿瘤坏死因子-α(TNF-α)基因-238位点G／A单核苷酸多态性与乙型肝炎病毒(HBV)宫内感染易感性的关系。方法 应用实时荧光定量聚合酶链反应技术检测HBV标志物阳性母亲所生45例HBV宫内感染儿童(Ⅰ组)、85例宫内未感染儿童(Ⅱ组)和126例对照组儿童TNF-α基因-238位点G／A单核苷酸多态性。结果 HBV宫内感染组TNF-α基因-238位点A等位基因频率显著高于HBV宫内未感染组(X^2=6．797，P=0．009)和对照组(X^2=9．513，P=0．002)，HBV宫内未感染组和对照组之间差异无显著性(X^2=0．047，P=0．828)。结论 TNF-α基因启动子区-238位点A等位基因与HBV宫内感染易感性相关，可作为检测其遗传易感性的标志之一。     

IL-1β和IL-1Ra基因单核苷酸多态性同溃疡性结肠炎的相关性

目的探讨白细胞介素113（IL-1β）和白细胞介素1受体结抗剂（IL-1Ra）基因单核苷酸多态性（SNP）与溃疡性结肠炎（UC）易感性的关系。方法应用聚合酶链式反应顺序特异性引物法（PCR—SSP），检测2005年5月至2006年8月在哈尔滨医科大学附属第一医院就诊的56例UC患者和44例同期健康体检者的IL-1β（-511T／C）位点、IL-1β（＋3962T／C）位点和IL-1Ra（11100C／T）位点的SNP，分析两组基因型频率和等位基因频率差异；并分析两组差异显著基因的单倍体分型以及基因型与表型的关系。结果（1）UC组IL-1β＋3962位点TC杂合子基因型频率及T等位基因频率明显高于对照组，差异有显著性（P=0．000，P=0．02）。OR值分析表明IL-1β＋3962位点为TC基因型的人群患UC的风险性是TT或CC基因型人群的2．4倍。（2）单倍体分型显示，含有IL-1β＋3962T等位基因（IL-1β511C3962T）的H1单倍型和含有野生型等位基因（IL-1β511C3962C）的H2单倍型在两组中频率的比较差异具有显著性。（3）IL-1β＋3962位点各基因型在UC患者不同病情轻重之间的分布比较以及不同发病部位之间的分布比较差异无显著性；（4）IL-1β-511位点和IL-1Ra 11100位点基因型频率和等位基因频率在两组人群中的分布差异无显著性。结论①IL-1β＋3962位点CT基因型频率及T等位基因频率增高可能与UC易感性有关，但与UC患者病情轻重及发病部位无关。②IL-1β保留511位点和IL-1RA 11100位点的SNP与UC易感性无关。     

HBsAg阳性孕产妇IL28B基因多态性与HBV宫内感染发生风险关联性分析

目的探究HBsAg阳性孕产妇白细胞介素28B(IL28B)基因多态性(SNP)与发生HBV宫内感染的关联性。方法选取单胎足月HBsAg阳性孕产妇为研究对象,并根据是否发生HBV宫内感染分为感染组(658例)与未感染组(1342例),另以542例正常孕妇为对照组。采用四引物扩增受阻突变体系聚合酶链反应(ARMS-PCR)检测IL28B rs8099917位点基因型,采用酶联免疫吸附法(ELISA)检测并比较IL28B rs8099917位点各基因型患者血清IL-17、IL-21、IL-4、转化生长因子-β1(TGF-β1)、γ干扰素(IFN-γ)水平,采用Logistic法分析IL28B rs8099917位点基因型与发生HBV宫内感染的关系。结果 IL28B rs8099917位点存在野生型纯合子TT型、突变杂合子TG型、突变纯合子GG型,且各组中IL28B基因型分布均符合Hardy-weinberg平衡定律。感染组G等位基因频率显著高于T等位基因频率(P0.05),而未感染组与对照组比较差异无统计学意义(P0.05);与未感染组、对照组比较,感染组血清IL-17、IL-21、TGF-β1、IL-4水平均显著升高(P0.05),其中TG与GG型显著高于TT型(P0.05),且GG型显著高于TG型(P0.05),而IFN-γ水平显著降低(P0.05),且GG型显著低于TG与TT型(P0.05),但未感染组与对照组比较差异无统计学意义(P0.05)。Logistic分析显示GG基因型为HBV宫内感染发生的危险因素。结论 HBsAg阳性孕产妇IL28B SNP与HBV宫内感染有关,GG基因型可增加HBV宫内感染发生风险。     

云南哈尼族彝族幽门螺杆菌感染人群胃癌易感基因研究

胃癌的发生是生物、环境、宿主等因素共同作用的结果．宿主遗传因素与幽门螺杆菌（H．pylori）感染后的不同临床结局有关。目的：筛选云南红河州哈尼族彝族Hpylori感染人群的胃癌易感基因,探讨不同基因型和等位基因与H．pylori感染宿主胃癌发病风险的相关性。方法：通过PubMed、CNKI和HapMap数据筛选出12个中国人群胃癌易感相关单核苷酸多态性（SNP）位点,以芯片技术对哈尼族彝族H．pylori感染慢性胃炎和胃癌患者的这些SNP位点进行分型。结果：IL-1β-3IC／T和IL-1β-511C/T位点存在完全连锁不平衡．其基因型（P=0．014）和等位基因频率（P=0．049）在胃癌和胃炎组中有显著差异,-511CT／-31CT（OR=2．256,95％CI：1．048～4．855）和-511TT/-31CC（OR=3．312,95％CI：1．462～7．502）基因型胃癌发病风险显著高于-511CC／-31TT基因型。COX-2．899C／G位点基因型频率在胃癌和胃炎组中有显著差异（P=0．033）,GG基因型胃癌发病风险显著高于CG基因型（OR=2．796,95％CI：1．053～7．423）。TNF—α-238A／G位点基因型频率在胃癌和胃炎组中有显著差异（P=0．037）．AA、AG基因型胃癌发病风险显著高于GG基因型（OR=2．600．95％CI：1．130～5．985）。结论：IL-1β-31C、IL-1β-511T等位基因和COX-2—899GG基因型可增高云南红河州哈尼族彝族Hpylori感染人群的胃癌发病风险,TNF-α-238GG基因型对上述人群的胃癌发生具有保护作用。     

ICAM-1基因多态性与HBV感染不同临床结局之间的关系

目的探讨细胞间黏附分子l（ICAM-1）基因多态性与HBV感染不同临床结局之间的相关性。方法应用病例．对照研究和聚合酶链反应-序列特异性引物法（PCR-SSP）检测118例慢性持续性HBV感染患者（包括无症状HBV携带者、慢性乙型肝炎、乙肝后肝硬化患者）和60例HBV急性自限性感染者的ICAM-1基因G241R（G／A）、K469E（A／G）两个位点的多态性，比较各组间基因型和等位基因频率，并对数据进行统计分析。结果①ICAM-l G241R（G／A）位点总GG基因型频率在HBV慢性持续性感染组高于急性自限性感染组，但差异无统计学意义（X^2=1．38，P〉0．05）。②ICAM-1 K469E（A／G）位点，进展性肝病组（慢性乙型肝炎和肝硬化）总KK基因型和总K等位基因的频率与无症状携带者组和自限性感染组相比显著增高（X^2=8．60，P〈0．05；X^2=5．07，P〈0、05），而在自限性感染和无症状携带者之间却无显著差异。结论携带ICAM-1 K469E KK基因型和K等位基因的患者容易进展成慢性乙型肝炎甚至肝硬化，可致慢性HBV感染患者病情进展。     

Ⅱ类反式激活因子启动子Ⅳ区C-1350T和G-944C多态性与乙型肝炎肝硬化易感性的关系

目的探讨Ⅱ类反式激活因子（CIITA）启动子Ⅳ区1350和-944位点单核苷酸多态性（SNP）与乙型肝炎肝硬化易感性的关系。方法在191例慢性乙型肝炎、353例乙型肝炎肝硬化与125名无HBV感染的健康献血员人群中，应用序列特异性引物PCR技术对CIITA基因启动子Ⅳ区C1350T和G-944C位点进行基因分型研究。结果慢性乙型肝炎患者CC：37．2％、TG：42．2％、CG：18．9％，肝硬化患者CC：35．3％、TG：34．0％，CG：29．3％，肝硬化患者CC、TG单倍型频率较低，而CG单倍型频率显著升高，差异有统计学意义（CG比CC：x^2=8．274，df=1，P〈0．01；CG比TG：x2=15．027，df=1，P〈0．01）；两组患者间CC与TG单倍型频率比较，x^2=1．231，df=1，P〉0．05，差异无统计学意义。与慢性乙型肝炎患者（CC／CC：12．6％；TG／TG：18．3％；含CG的基因型：33．5％；不含CG的基因型：35．6％）相比，肝硬化人群中CC／CC（1组，19．6％）和含CG的基因型（3组，53．5％）频率显著升高，而TG／TG（2组，11．9％）和不含CG的基因型（4组，15．0％）频率显著降低（1组比2组，X2=7．176，df=1，P〈0．01；1组比4组，x^2=19．818，df=1，P〈0．01；3组比2组，x2=11．423，df=1，P〈0．01；3组比4组，x2=34．226，df=1，P〈0．01；1组比3组，x2=0．009，df=1，P〉0．05；2组比4组，x2=2．176，df=1，P〉0．05）。结论CIITA基因启动子Ⅳ区中1350和-944位点多态性与慢性HBV感染者肝硬化的易感性密切相关，携带含CG单倍型的基因型人群更容易发展为肝硬化。     

干扰素-γ基因+874位点及肿瘤坏死因子-α基因-238位点单核苷酸多态性与HBV宫内感染相关性研究

目的:研究IFN-γ+874位点T/A以及TNF-α-238位点G/A的单核苷酸多态性与HBV宫内感染的相关性。方法:采集HBV标记物单项或多项阳性孕妇的外周血,提取基因组DNA,根据新生儿是否感染HBV将孕妇分为宫内感染组和对照组。利用等位基因特异性PCR检测IFN-γ+874位点等位基因型,利用PCR-RFLP方法检测TNF-α-238位点等位基因型。结果:等位基因特异性PCR可以准确判断IFN-γ+874位点等位基因型,对照组IFN-γ+874位点等位基因频率A为0.562,T为0.438,而宫内感染组A为0.738,T为0.262,两组之间的差异具有统计学意义(χ2=4.38,P=0.036)。TNF-α-238位点等位基因型的检测可以使用PCR-RFLP方法,对照组TNF-α-238位点等位基因频率A为0.146,G为0.854,宫内感染组A为0.262,G为0.738,两组之间的差异无统计学意义(χ2=3.26,P=0.071)。结论:IFN-γ+874位点T/A等位基因与HBV宫内感染具有一定相关性,T等位基因对胎儿HBV宫内感染具有防护作用。TNF-α-238位点G/A等位基因型与HBV宫内感染的关系尚不明确。     

白细胞介素-1基因族多态性与脑梗死的关系

目的探讨白细胞介素（IL）-1α及IL-1β基因多态性与脑梗死的关系。方法用聚合酶链反应-限制性片段长度多态性技术对110例脑梗死患者（梗死组）和110例健康者（对照组）的IL-1α-889C／T、IL-1β＋3953C／T及IL-1β-511C／T的基因多态性进行分析。结果梗死组IL-1α-889C／T和IL-1β＋3953C／T基因型的分布频率与对照组比较差异均有显著性（P=0．035，P=0．023）；梗死组IL-1α-889T、IL-1β＋3953T等位基因频率分别为13．2％和5．9％，与对照组的5．9％、1．8％比较差异有显著性（P=0．009，P=0．026）；IL-1β-511C／T的基因型频率及等位基因频率两组比较差异无显著性（P=0．891，P=0．634）。结论脑梗死患者IL-1α-889T及IL-1β＋3953T等位基因频率增高，IL-1α-889C／T、IL-1β＋3953C／T基因多态性与脑梗死的发病有关。     

白细胞介素10基因多态性与脑梗死的关系

目的探讨白细胞介素10（IL-10）基因多态性与脑梗死的关系。方法用聚合酶链反应一限制性片段长度多态性技术，对204例脑梗死患者（脑梗死组）和131名健康者（对照组）的IL-10-592C／A、IL-10-819C／T及IL-10．1082G／A，共3个位点的基因多态性进行分析。结果脑梗死组IL-10—1082G／A基因型的分布频率与对照组比较，差异有统计学意义（X^2=11．764，P=0．001）；IL-10-1082A等位基因频率为99．5％，对照组为95．8％，两组比较差异有统计学意义（P=0．001）；IL-10-592C／A和IL-10-819C／T的基因型分布频率及等位基因频率与对照组比较差异无统计学意义（P〉0．05）。结论IL-10—1082G／A基因多态性与脑梗死的发病有一定关系，其中A等位基因频率增高与脑梗死发病有关。     

白介素13基因多态性与哮喘发病易感性的关系

目的：探讨白介素13（IL-13）基因内含子区＋1923C/T多态性与哮喘发病易感性的关系。方法采用聚合酶链反应-限制性片段长度多态性技术对150例哮喘患者（哮喘组）和150例健康对照者（对照组） IL-13基因内含子区＋1923 C/T单核苷酸多态性进行检测,比较其基因型和等位基因分布频率。结果对照组IL-13基因内含子区＋1923 C/T基因型CC、CT和TT的分布频率分别为41．33％（62/150）、44．00％（66/150）和14．67％（22/150）,在哮喘组分别为21．33％（32/150）、41．33％（62/150）和37．34％（56/150）,两组各基因型分布频率比较差异有统计学意义（χ^2＝24．52,P＜0．01）。 CT、TT基因型者患哮喘的危险性高于CC基因型者（χ^2＝27．38,P＜0．01）。结论 IL-13基因内含子区＋1923 C/T多态性是影响哮喘发病的重要候选基因,T等位基因与哮喘易感性相关。     

Serum cytokine profile in patients with hepatitis B e antigen-negative chronic active hepatitis B and inactive hepatitis B virus carriers

An insufficient cellular immune response seems to be critical for the immunopathogenesis of chronic hepatitis B virus infection.We have previously demonstrated no differences of T-lymphocyte subsets in blood between inactive hepatitis B s antigen(HBsAg) carriers and patients with HBeAg-negative chronic active hepatitis B.This study investigated the peripheral blood cytokine profile in patients with HBeAg-negative chronic active hepatitis B infection(Group A,n = 21) and inactive HBsAg carriers(Group B,n = 13).Serum cytokines [interferon(IFN)-γ,tumor necrosis factor-α,interleukin(IL)-1b,IL-4,IL-12,IL-10,IL-2,IL-5,IL-8] were analyzed by using flow cytometry.Patients with chronic active disease presented with significantly decreased levels of IFN-γ and IL-10 compared to inac-tive carriers(P = 0.048 and P = 0.008,respectively).In HBeAg-negative chronic active hepatitis B patients,a significant negative correlation of IFN-γ levels with serum hepatitis B viral load was noted(P = 0.021).In conclusion,patients with HBeAg-negative chronic active hepatitis B and HBsAg inactive carriers display a different cytokine profile.Decreased Th1 response observed in patients with chronic active hepatitis B could be implicated in the persistence of virus replication and ongoing progression of liver disease.     

Penicillin susceptibility and macrolide-lincosamide-streptogramin B resistance in group B Streptococcus isolates from a Canadian hospital

BACKGROUND:

Intrapartum antibiotic prophylaxis (IAP) is recommended for pregnant women who test positive for group B Streptococcus (GBS) in their genitourinary tract to prevent GBS-induced neonatal sepsis. Penicillin G is used as the primary antibiotic, and clindamycin or erythromycin as the secondary, if allergies exist. Decreased susceptibility to penicillin G has occasionally been reported; however, clindamycin and erythromycin resistance is on the rise and is causing concern over the use of clindamycin and erythromycin IAP.

METHODS:

Antibiotic resistance was characterized phenotypically using a D-Test for erythromycin and clindamycin, while an E-Test (E-strip) was used for penicillin G. GBS was isolated from vaginal-rectal swabs and serologically confirmed using Prolex (Pro-Lab Diagnostics, Canada) streptococcal grouping reagents. Susceptibility testing of isolates was performed according to the Clinical Laboratory Standards Institute guidelines.

RESULTS:

All 158 isolates were penicillin G sensitive. Inducible macrolide-lincosamide-streptogramin B (MLSB) resistance was observed in 13.9% of isolates. Constitutive MLSB resistance was observed in 12.7% of isolates. M phenotype resistance was observed in 6.3% of isolates. In total, erythromycin resistance was present in 32.9% of the GBS isolates, while clindamycin resistance was present in 26.6%.

DISCUSSION:

The sampled GBS population showed no sign of reduced penicillin susceptibility, with all being well under susceptible minimum inhibitory concentration values. These data are congruent with the large body of evidence showing that penicillin G remains the most reliable clinical antibiotic for IAP. Clindamycin and erythromycin resistance was higher than expected, contributing to a growing body of evidence that suggests the re-evaluation of clindamycin and erythromycin IAP is warranted.     

Hepatitis B prevalence in emergency physicians

The seriousness of hepatitis B (HBV) as an occupational hazard to health care workers is well documented. The prevalence of serologic markers for this disease in the general US population is less than 5%, but in medical and dental workers it is significantly higher: 16% in general dentists, 28% in surgeons, 23% in anesthesia personnel, and 30% in emergency department nurses. This study, done under the auspices of the American College of Emergency Physicians (ACEP), focused on the prevalence of HBV markers in emergency physicians. Twenty-five percent of the 1983 ACEP Scientific Assembly attendees participated in the serosurvey. Physicians already vaccinated against hepatitis B were excluded. The majority of participants (58%) were community emergency physicians between 30 and 39 years of age who had six or more years in emergency medicine. A total of 94% of the physicians indicated no prior history of hepatitis, and of these 13.1% had serologic markers for HBV. Including the 10 physicians with both HBV markers and history of hepatitis, the overall prevalence for markers in this study was 15.5%. This prevalence was five times greater than the general population. Emergency physicians should be considered a high-risk group for HBV infection.     

Lamivudine plus low-dose hepatitis B immunoglobulin to prevent recurrent hepatitis B following liver transplantation

BACKGROUND AND AIMS: High-dose intravenous hepatitis B immunoglobulin (HBIG) may prevent recurrent hepatitis B virus (HBV) infection, but the cost has limited its widespread use in countries with endemic HBV infection. We report on long-term safety and efficacy of an alternative strategy of very low doses (400-800 IU/month) of intramuscular (IM) HBIG plus lamivudine. METHODS: Australian and New Zealand patients who received low-dose HBIG plus lamivudine following liver transplantation for HBV-related end-stage liver disease were studied. Prior to transplantation, patients with detectable serum HBV DNA received lamivudine 100 mg daily. Posttransplantation, all patients received lamivudine 100 mg daily plus IM HBIG 400 or 800 IU daily for 1 week then monthly thereafter. Serum HBV DNA levels were measured prior to lamivudine, at transplantation, and at 12 months posttransplantation. Serum titers of antibody to HBV surface antigen were measured at 1, 3, and 12 months posttransplantation. RESULTS: Between February 1996 and October 2004, 147 patients received low-dose HBIG plus lamivudine. Thirty-one percent were hepatitis B e antigen positive, and 85% were HBV DNA+ prior to transplantation. The median duration of pretransplantation lamivudine was 92 days (range, 1-1775). Median follow-up posttransplantation was 1860 days. Kaplan-Meier patient survival was 92% at 1 year and 88% at 5 years. The actuarial risk of HBV recurrence was 1% at 1 year and 4% at 5 years. Baseline HBV DNA titer was associated with HBV recurrence. CONCLUSION: Low-dose IM HBIG plus lamivudine provides safe and effective long-term prophylaxis against recurrent HBV at <10% the cost of the high-dose regimen.     

Hepatitis B virus reactivation with rituximab-containing regimen

Rituximab is recognized as a useful drug for the treatment of B-cell non-Hodgkin’s lymphoma and its use has been extended to such diseases as idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, chronic rheumatoid arthritis and ANCA-associated vasculitides. One serious complication associated with its use is the reactivation of hepatitis B virus and the search for methods to prevent this occurrence has resulted in the rapid accumulation of knowledge. In this review, we discuss case analyses from our department and other groups and outline the current knowledge on the topic and the remaining issues.