Parental smoking and the risk of childhood asthma.

Data from two random population surveys are used to assess the relationship between parental smoking and the prevalence of asthma in children aged 0-17. Data from a 1977 Midwestern urbanized county indicate that, if mothers smoked, the prevalence of parent reported asthma increased from 5.0 per cent to 7.7 per cent (estimated relative risk of 1.5), and the prevalence of functionally impairing asthma increased from 1.1 per cent to 2.2 per cent (relative risk of 2.0). In a more rural Eastern county in 1980, a lower overall prevalence of asthma was noted. However, similar estimated relative risks of asthma (1.8) and functionally impairing asthma (2.4) were found to be associated with maternal smoking. Inconsistent relationships were found between the estimated prevalence of asthma and paternal smoking. When multivariate controls were introduced, the relationships between maternal smoking and asthma persisted. Estimated attributable risks indicate that between 18 per cent and 34 per cent of the asthma reported in these samples can be attributed to maternal smoking. Implications of these findings for primary care physicians are discussed.     

妊娠期糖尿病患者血清TNF-α浓度与空腹血糖水平的相关性研究

1829年Astley Cooper首次报道乳腺结核病例。1860年Lan—Ceraux首先以病理检查诊断此病。1868年Culaeo从患者脓液中分离出结核杆菌并动物接种成功。乳腺结核为乳腺组织的慢性特异性感染，多见于南非和印度，约占乳腺疾病的4．5％，国内报道为2．8％，欧美乳腺结核发病率为0．5％-1．0％。由于其在临床上少见，临床表现多样，缺乏特异性，且各种检测方法各有局限，误诊率可为57％-80％，因此其诊断与治疗值得进一步探讨。     

Parental smoking and the risk of childhood leukemia

Cigarette smoke has been linked to adult myeloid leukemia; however, the association between parental smoking and childhood leukemia remains unclear. Parental smoking and the risk of childhood leukemia were examined in the Northern California Childhood Leukemia Study, a case-control study, between 1995 and 2002. The present analysis included 327 acute childhood leukemia cases (281 acute lymphoblastic leukemia (ALL) and 46 acute myeloid leukemia (AML)) and 416 controls matched on age, sex, maternal race, and Hispanic ethnicity. Maternal smoking was not associated with an increased risk of either ALL or AML. Paternal preconception smoking was significantly associated with an increased risk of AML (odds ratio = 3.84, 95% confidence interval: 1.04, 14.17); an increased risk for ALL was suggestive for paternal preconception smoking (odds ratio = 1.32, 95% confidence interval: 0.86, 2.04). Greater risks of ALL were observed compared with the risk associated with paternal preconception smoking alone, when paternal preconception smoking was combined with maternal postnatal smoking (p(interaction) = 0.004) or postnatal passive smoking exposure (p(interaction) = 0.004). These results strongly suggest that exposure to paternal preconception smoking alone or in combination with postnatal passive smoking may be important in the risk of childhood leukemia.     

肿瘤坏死因子-α基因多态性与早产

肿瘤坏死因子-α是一种具有多种生物学活性的多功能细胞因子,其编码基因具有多态性,这些多态性可以从转录水平上影响肿瘤坏死因子-α的表达,并与个体对疾病的易感性、发展、预后相关。研究表明早产患者羊水、血清、组织中肿瘤坏死因子-α表达量显著升高。该文就肿瘤坏死因子-α基因多态性与早产的相关性作以综述。     

被动吸烟与儿童哮喘关系的Meta分析

目的:探讨被动吸烟与儿童哮喘的关系。方法:采用ReviewManager4·2分析软件,对国内外15篇有关被动吸烟与儿童哮喘关系的病例对照结果进行了随机效应模型的Meta分析。结果:被动吸烟与儿童哮喘的发生关联明显(Z=4·93,P<0·00001),合并OR值为1·51,OR95%CI为1·28~1·77。结论:被动吸烟是儿童哮喘发生的一个危险因素。     

The associations between childhood asthma and atopy, and parental asthma, hay fever and smoking

Summary. The aim of this analysis was to examine the degree to which a life time prevalence of asthma in a 7-year-old child is statistically associated with atopic conditions of the child, and with parental asthma, hay fever and smoking. In 1968, 8585 children who were born in 1961 and who were attending school in Tasmania were surveyed. This comprised 99% of the eligible population. The prevalence of a history of asthma in the 7-year-olds was 16.2% (males 19.0%, females 13.2%). Multiple logistic regression analysis showed that a history of asthma in a 7-year-old was associated with the child being male (odds ratio [OR] 1.56; 99% confidence interval 1.30–1.86), having a history of hay fever (3.86; 3.12–4.78), eczema (2.04; 1.63–2.55), hives (1.34; 1.09–1.65) or allergy to foods or medicines (1.70; 1.26–2.30), the child's mother or father having a history of asthma (2.63; 2.08–3.31 or 2.52; 1.99–3.19, respectively), and the mother being a smoker (1.26; 1.05–1.51). Parental hay fever and paternal smoking were not independently associated with childhood asthma. The strength of association between childhood asthma and parental asthma was independent of the sex of either the parent or the child, and of atopic conditions in the child. In the 133 children for whom both parents were asthmatic, 65 (49%) had a history of asthma. These findings, based on a population survey, are consistent, not only with a childhood history of asthma being strongly associated with atopy, but also with the existence of strong unmeasured determinants common to family members, the effects of which are not mediated via atopy. The risk for asthma being independent of both the sex of the child and of the parent, is consistent with a genetic aetiology for susceptibility to asthma.     

重型肝炎肝性脑病患者血氨和肿瘤坏死因子-α的相关性研究

目的 研究重型肝炎肝性脑病患者血氨和TNF-α的相关性.方法 采用ELISA法检测60例重型肝炎患者血清TNF-α含量,用酶法测定静脉血氨值.结果 在肝性脑病0级(15例)患者中血氨和TNF-α分别是(39.1±6.5)μmol/L和(72.34±7.25)ng/L,Ⅰ级(10例)分别是(55.3±9.2)μmol/L和(91.25±10.16)ng/L,Ⅱ级(16例)分别是(82.5±12.5)μmol/L和(128.25±13.45)ng/L,Ⅲ级(13例)分别是(124.6±21.3)μmol/L和(155.38±19.76)ng/L,Ⅳ级(6例)分别是(198.3±36.7)μmol/L和(186.39±23.54)ng/L.血氨和TNF-α之间具有显著的相关性(r=0.68.P＜0.01),并且血氨和TNF-α与肝性脑病的严重程度具有明显的相关性(r=0.91,P＜0.01和r=0.85.P＜0.01).结论 重型肝炎肝性脑病患者血氨和TNF-α具有显著的相关性,TNF-α可能参与肝性脑病的发病机制.     

Maternal smoking in pregnancy, fetal development, and childhood asthma

OBJECTIVES: We examined the relationships among maternal smoking in pregnancy, fetal development, and the risk of asthma in childhood. METHODS: We conducted a population-based cohort study, where all 58 841 singleton births were followed for 7 years using nationwide registries. RESULTS: Maternal smoking increased the risk of asthma (adjusted odds ratio = 1.35; 95% confidence interval = 1.13, 1.62 for high exposure). Low birthweight and preterm delivery increased the risk of asthma at the age of 7, whereas being small for gestational age did not. CONCLUSIONS: Maternal smoking in pregnancy increases the risk of asthma during the first 7 years of life, and only a small fraction of the effect seems to be mediated through fetal growth.     

肿瘤坏死因子-a及其Ⅱ型受体基因多态性与矽肺

目的探讨肿瘤坏死因子-a(TNF-a)及其Ⅱ型受体(TNFRⅡ)基因多态性在矽肺发病遗传易感性中的作用及其与二氧化硅暴露的交互作用.方法选择259例矽肺患者和341例矽尘接触者(对照)为研究对象,对其职业史、尘肺病史、既往病史等进行问卷调查;拍摄其高仟伏X射线后前位胸片,根据尘肺病诊断标准进行诊断和分期;采集每个研究对象的外周静脉血,应用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术检测其TNF-a及TNFRⅡ基因多态性.结果在成组或11配对分析中,矽肺患者和矽尘接触者两组间TNF-a基因-308位点G/A+A/A基因型和TNFRⅡ196位点T/G+G/G基因型分布频率的差异均无统计学意义(P＞0.05).当接尘工龄＜15年时,G/A+A/A基因型携带者发生矽肺的危险性是G/G基因型的6.74倍,95%CI1.01～44.99.结论TNF-α和TNFRⅡ基因多态性在汉族人群矽肺发病的遗传易感性中不起主要作用.TNF-α基因-308位点基因多态性在矽肺发病过程中与接尘工龄存在交互作用,当累积接尘量较低时,G/A+A/A基因型携带者发生矽肺的危险性较G/G基因型明显增加.     

燃煤型室内空气污染物与儿童哮喘易感基因的关系研究

目的了解贵州省贵定县哮喘儿童居室内燃煤型空气污染物(PM4、SO2、CO)的暴露水平和哮喘儿童中β2肾上腺素能受体(β2-AR)基因第16、27位点以及血管紧张素转移酶(ACE)基因的分布频率,揭示燃煤型空气污染物和哮喘易感基因的交互作用与儿童哮喘发病风险的关系。方法采用单纯病例研究的流行病学方法,通过PCR方法检测231个哮喘患儿的β2肾上腺素能受体(β2-AR)基因第16、27位点多态性和血管紧张素转移酶(ACE)基因插入/缺失(I/D)多态性以及哮喘儿童家庭居室内空气中PM4、SO2、CO的浓度,计算两种哮喘易感基因多态性的分布频率,并判断PM4、SO2、CO与β2-AR基因第16、27位点多态性以及血管紧张素转移酶(ACE)基因插入/缺失(I/D)多态性在儿童哮喘的发生中是否存在相乘模型的交互作用。结果哮喘儿童的燃煤型空气污染物暴露率为87.4%(202人);β2-AR基因16位点Arg/Arg纯合子、Gly/Gly纯合子、Arg/Gly杂合子在哮喘儿童中的分布频率分别为13.9%、13.4%和72.7%;27位点Gln/Gln纯合子、Glu/Glu纯合子、Gln/Glu杂合子的频率分别为13.9%、4.3%和81.8%,ACE基因Ⅱ、DD和ID基因型的频率分别为49.3%、20.0%和30.7%。PM4、SO2、CO和β2-AR基因多态性以及ACE基因多态性在儿童哮喘的发生中存在相乘模型的交互作用(均P<0.05)。结论当地乡村燃煤型室内空气污染问题较为突出;三种哮喘易感基因多态性的频率分布在当地有一定特殊性;煤型空气污染物(PM4、SO2、CO)与β2-AR基因16位点Gly/Gly基因型和ACE基因DD基因型的交互作用可能增加儿童哮喘发生的危险性。     

亚临床甲状腺功能减退症患者血清C反应蛋白、肿瘤坏死因子-α及动脉粥样硬化关系的研究

目的 探讨亚临床甲状腺功能减退症(亚临床甲减)患者血清C反应蛋白(CRP)、肿瘤坏死因子β (TNF-α)及动脉粥样硬化的关系.方法 75例亚临床甲减患者根据促甲状腺激素(TSH)水平分为两组:轻度亚临床甲减(TSH 5.5～10.0 mU/L)组42例,重度亚临床甲减(TSH＞ 10.0mU/L)组33例;另选取健康体检者或志愿者30例作为对照组.所有受检者均检测三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、TSH、游离甲状腺素(FT4)、游离三碘甲腺原氨酸(FT3)、CRP 以及TNF-β,并测量颈动脉内膜-中层厚度(CIMT).结果 轻度亚临床甲减组、重度亚临床甲减组、对照组CIMT分别为(0.88±0.20)、(1.12±0.21)、(0.62±0.21)mm,轻度亚临床甲减组、重度亚临床甲减组CIMT均高于对照组,重度亚临床甲减组CIMT高于轻度亚临床甲减组,差异均有统计学意义(P＜0.01).三组 CRP、TNF-α比较差异无统计学意义(P＞0.05).轻度亚临床甲减组、重度亚临床甲减组 LDL-CC[( 3.22±0.37)、(3.49±0.38)mmol/L]均高于对照组[(2.48±0.41 )mmol/L],差异有统计学意义(P＜0.01);对照组、轻度亚临床甲减组 HDL-C、TG比较差异无统计学意义(P＞0.05);与对照组、轻度亚临床甲减组比较,重度亚临床甲减组HDL-C降低[(0.92±0.10)mmol/L比(1.21±0.14)、( 1.17±0.11) mmol/L],TG 增高[(1.50±0.49) mmol/L比(1.11±0.53)、(1.27±0.47) mmol/L],差异有统计学意义(P＜0.01或＜0.05).TG、LDL-C、TSH、CRP、TNF-α与CIMT 呈正相关(r=0.52、0.37、0.48、0.39、0.45,P＜0.05或＜0.01);FT4与CIMT 呈负相关(r=-0.24,P＜0.05);HDL-C与CIMT无相关性(r=0.06,P＞0.05).结论 亚临床甲减患者存在血脂代谢紊乱等多种异常,其发生动脉粥样硬化危险性增高,但炎性反应可能不是亚临床甲减并发动脉粥样硬化的主要因素.     

Ethanol increases tumor necrosis factor-alpha receptor-1 (TNF-R1) levels in hepatic, intestinal, and cardiac cells.

Chronic ethanol consumption leads to cell injury in virtually every tissue. Tumor necrosis factor-alpha (TNF-alpha) constitutes a major factor in the development of alcohol-induced liver injury. In alcohol-dependent subjects, elevated levels of plasma TNF-alpha are strongly predictive of mortality. Binding of TNF-alpha to TNF-alpha receptor-1 (TNF-R1) activates death domain pathways, leading to necrosis and apoptosis in most tissues, and it also increases the expression of intercellular adhesion molecules (i.e., ICAM-1), which promote inflammation. We determined whether ethanol exposure leads to increases in cellular TNF-R1. We incubated HepG2 human hepatoma cells and H4-II-E-C3 rat hepatoma cells with 25, 50, and 100 mM ethanol for various intervals of time up to 48 h. Human colonic adenocarcinoma cells (Caco-2 cells) and neonatal rat primary cardiomyocytes were also incubated with different concentrations of ethanol. Levels of TNF-R1 were measured either by a sandwich enzyme-linked immunosorbent assay (ELISA) method or by determining the extracellular transmembrane domain of TNF-R1 by an intact-cell ELISA method. Ethanol exposure for 48 h increased TNF-R1 levels in human hepatoma cells in a dose-dependent manner. Levels increased significantly by 164% at 50 mM and by 240% at 100 mM ethanol. Effects were time dependent and did not reach a plateau at 48 h. Similar increases in TNF-R1 were also observed in rat hepatoma cells (90% at 50 mM and 230% at 100 mM ethanol). Under similar conditions, Caco-2 cells showed a significant 80% increase in TNF-R1 levels at 200 mM ethanol, a concentration found in intestine. Neonatal rat primary cardiomyocytes showed TNF-R1 increases of 36% at 50 mM and 44% at 100 mM ethanol. These results indicate that exposure of different cell types to pharmacologic concentrations of ethanol increases TNF-R1 levels and may augment TNF-alpha-mediated cell injury in different tissues.     

Longitudinal study of parental smoking habits and development of asthma in early childhood

Objective

This study examined the association between parental smoking habits and the development of asthma in early childhood by using representative samples.

Methods

The survey subjects included all of the 53,575 babies born in Japan during the periods January 10-17 and July 10-17, 2001. The families of the subjects were asked to complete questionnaires that were delivered by post at 6 months, 1 year 6 months, 2 years 6 months, 3 years 6 months, and 4 years 6 months postpartum. The first survey contained questions regarding the smoking habits of the parents. The second to fifth surveys asked if the child had needed medical attention for the treatment of asthma.

Results

Data from 36,888 subjects (collection rate: 68.9%) were analyzed. The 4-year cumulative incidence of asthma was 12.0%. Maternal indoor smoking significantly increased the risk of asthma development in children, 4-year risk 14.4% vs. 11.7%, risk ratio = 1.24, 95% CI: 1.11 to 1.38. No statistically significant association was found between paternal smoking and asthma development in children.

Conclusions

In order to prevent the development of asthma in early childhood, it is necessary to formulate measures to stop or discourage maternal smoking.     

Prevalence of asthma and wheeze in relation to passive smoking in Japanese children

PURPOSE: Evidence remains inconclusive as to whether environmental tobacco smoke is a risk factor for allergic disorders in childhood. The present large-scale cross-sectional study examined the relationship between passive smoking at home and the prevalence of allergic disorders in Japanese schoolchildren. METHODS: Study subjects were 23,044 children aged 6 to 15 years in Okinawa. Outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Adjustment was made for sex, age, region of residence, number of siblings, paternal and maternal history of asthma, atopic eczema, or allergic rhinitis, as well as paternal and maternal educational level. RESULTS: The prevalence of wheeze, asthma, atopic eczema, and allergic rhinoconjunctivitis in the previous 12 months was 10.7%, 7.6%, 6.8%, and 7.7%, respectively. Current heavy passive smoking and 7.0 or more pack-years of smoking in the household were independently related to an increased prevalence of wheeze and asthma, especially in children 6 to 10 years of age and children with a positive parental allergic history. There was no dose-response relationship between pack-years of smoking in the household and atopic eczema or allergic rhinoconjunctivitis. CONCLUSIONS: Our findings suggested that environmental tobacco smoke might be associated with an increased prevalence of wheeze and asthma in Japanese children.     

Genetic polymorphisms of tumor necrosis factor-alpha modify the association between dietary polyunsaturated fatty acids and fasting HDL-cholesterol and apo A-I concentrations

BACKGROUND: Heterogeneity in circulating lipid concentrations in response to dietary polyunsaturated fatty acids (PUFAs) may be due, in part, to genetic variations. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that can induce hyperlipidemia and is known to be modulated by dietary PUFAs. OBJECTIVE: The objective was to determine whether TNF-alpha genotypes modify the association between dietary PUFA intake and serum lipid concentrations. DESIGN: The study involved 53 men and 56 women aged 42-75 y with type 2 diabetes. Dietary intakes were assessed with the use of a 3-d food record, and blood samples were collected to determine fasting serum lipids. DNA was isolated from blood for genotyping by polymerase chain reaction-restriction fragment length polymorphism for the TNF-alpha -238G-->A and -308G-->A polymorphisms. RESULTS: PUFA intake was positively associated with serum HDL cholesterol in carriers of the -238A allele (beta = 0.06 +/- 0.03 mmol/L per 1% of energy from PUFAs; P = 0.03), but negatively associated in those with the -238GG genotype (beta = -0.03 +/- 0.01, P = 0.03) (P = 0.004 for interaction). PUFA intake was inversely associated with HDL cholesterol in carriers of the -308A allele (beta = -0.07 +/- 0.02, P = 0.002), but not in those with the -308GG genotype (beta = 0.02 +/- 0.02, P = 0.13) (P = 0.001 for interaction). A stronger gene x diet interaction was observed when the polymorphisms at the 2 positions (-238/-308) were combined (P = 0.0003). Similar effects were observed for apolipoprotein A-I, but not with other dietary fatty acids and serum lipids. CONCLUSION: TNF-alpha genotypes modify the relation between dietary PUFA intake and HDL-cholesterol concentrations. These findings suggest that genetic variations affecting inflammation may explain some of the inconsistencies between previous studies relating PUFA intake and circulating HDL.     

转铁蛋白和肿瘤坏死因子-α的联合检测在肺结核化疗中的应用研究

目的 通过转铁蛋白(TRF)和肿瘤坏死因子-α(TNF-α)的联合检测,指导铁剂辅助的抗结核化疗,并对其应用价值进行研究.方法 肺结核患者随机均分为A和B两组,A组进行正规抗结核化疗,B组进行铁剂辅助的抗结核化疗,监测其疗效和TRF和TNF-α水平的变化.结果 在治疗各时间段,B组病灶显著吸收率、空洞闭合率显著高于A组(P＜0.05),痰菌涂片转阴率略高于A组(P＞0.05),TRF水平显著低于A组(P＜0.05),TNF-α水平略低于A组(P＞0.05).结论 TRF和TNF-α的联合检测可以帮助了解机体的铁代谢和抗结核免疫状况,铁剂辅助的抗结核化疗可帮助改善肺结核患者细胞免疫功能,提高临床治疗效果.     

皖籍汉族人寻常型银屑病患者TNF-α基因多态性分析

目的　探讨TNF α基因多态性与皖籍汉族人寻常型银屑病的相关性。方法　采用PCR RFLP方法 ,检测皖籍汉族人 6 5例早发型 (Ⅰ型 )银屑病、2 2例迟发型 (Ⅱ型 )银屑病及 1 2 8例健康人TNFα- 2 38多态性。结果　早发型银屑病患者携带TNFα - 2 38.2 (TNF G/A基因型 )频率较对照组明显增高 (2 6 .2 %vs 1 0 .9% ) ,二者差异有显著性 (OR =2 .88,Pc<0 .0 5 ) ;而迟发型银屑病患者携带该基因型频率则与对照组差异无显著性 (9.1 %vs 1 0 .9% ,OR =0 .81 ,Pc>0 .0 5 )。但早发型银屑病男女患者携带TNFα- 2 38.2频率与相应对照组差异均无显著性 (Pc>0 .0 5 )。结论　TNFα- 2 38.2频率与皖籍汉族人寻常型银屑病发病类型明显关联 ,提示TNF α基因多态性可能为汉族人银屑病易感因子之一。     

Tumour necrosis factor-alpha (TNF-alpha) in patients who have asbestosis and develop cancer.

OBJECTIVES--Concentrations of tumour necrosis factor-alpha (TNF-alpha) were assayed by radioimmunoassay in serum samples collected between 1981 and 1987 from 111 patients with asbestosis who were at a high risk of cancer. Follow up of these patients until 1993 showed that 38 had developed cancer (27 lung, three mesotheliomas, and eight diverse malignancies). RESULTS--The mean serum concentrations of TNF-alpha given in fmol/100 microliters serum in all the cases with cancer (14.1) and the cases with lung cancer (13.6) were significantly higher (P < 0.05) than the mean concentrations in the exposed controls (10.5). A positive increase was considered to be any value that was > 2 SDs above the mean of the exposed controls. 22% (six of 27) of the cases with lung cancer were positive compared with 4% (three of 73) of the exposed controls, a significant difference (P < 0.001). The serum concentrations of TNF-alpha correlated moderately with cancer (r = 0.3), lung cancer (r = 0.3), and Neu oncoproteins and epidermal growth factor receptor (EGFR) (r = 0.3, 0.5 respectively). Also, there was a significant correlation between development of cancer and severity or progression of asbestosis. There was no correlation between the concentrations of TNF-alpha and severity or progression of asbestosis. CONCLUSIONS--These results showed high concentrations of TNF-alpha in the patients who had cancer. TNF-alpha may offer an auxiliary method in early diagnosis of cancers related to asbestosis.