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Inflammatory response to coronary artery bypass surgery: Does the heme-oxygenase-1 gene microsatellite polymorphism play a role?

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Chinese Medical Journal 2005年第15期118卷 1285-1290页

作者： LI Ping Jules Sanders Emma Hawe David Brull hugh montgomery Steve Humphries Cardiovascular Department Second Affiliated Hospital of Jiangxi Medical College Nanchang 330006 China Centre for Cardiovascular Genetics British Heart Foundation Laboratories Department of Medicine Royal Free ＆ University College London Medical School Rayne Building 5 University Street London WC1E 6JF UK

Background Heme-oxygenase 1 （HO-1） is a rate-limiting enzyme in the degradation of heme to bilirubin, ferritin and carbon monoxide （CO） and may have significant anti-inflammatory function. The HO-1 gene promoter region shows microsatellite polymorphism with different （GT）n repeats, reported to differently induce gene expression, with the short allele associated with higher gene expression. We measured the acute inflammatory response using coronary artery bypass surgery （CABG） as a well-characterized and uniform stimulus and examined the correlation between levels of IL-6, C-reactive protein （CRP） and fibrinogen and their relationship to HO-1 genotype. Methods Two hundred and seventy-five consecutive patients undergoing CABG were genotyped for the HO-1 promoter polymorphism using PCR and automated DNA capillary sequencer. IL-6, CRP and fibrinogen were measured at baseline and 6, 24, 48, 72, 96 and 120 hours after CABG. Results Complete IL-6, CRP and fibrinogen measures were available in 220 patients. Before surgery IL-6 levels showed a strong correlation with CRP and fibrinogen （ r = 0. 48, P 〈 0. 0001 ; r = 0. 41, P 〈 0. 0001 respectively）, with a significant correlation between CRP and fibrinogen （r=0. 61, P 〈 0. 0001 ）. All three acute phase reactants showed a significant increase after CABG. After surgery, peak IL-6 was strongly correlated with peak CRP （r=0. 34, P =0.0009） but not with peak fibrinogen （r=0. 15, P =0. 13 ）, while peak CRP and peak fibrinogen were significantly correlated （r = 0. 15, P 〈 0. 0001 ）. HO-1 allelic repeats ranged from 22- 42, with （GT）25 and （GT）32 being the two most common alleles, and subsequently divided into three groups according to previous published work：〈 30 （GT） n were designated as S （short） , 30 - 37 （GT） n as M （middle） and long repeats with 〉 37 （GT） n as L （long） ; allele frequency 0. 35, 0. 58 and 0.07 respectively. Baseline CRP differed by genotype： those carrying at least one long allele having higher CRP than those

关键词： heine oxygenase polymorphism inflammation bypass surgery

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血红素氧化酶1基因多态和冠状动脉旁路移植后的炎症反应

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中国组织工程研究与临床康复 2009年第22期13卷 4261-4265页

作者：李萍 Jules Sanders Emma Hawe David Brull Jutta Palmen Jayshree Achary hugh montgomery Steve E.Humphries 南昌大学第二附属医院心血管内科江西省南昌市330006 英国伦敦大学学院心血管遗传病学中心

背景:血红素氧化酶1是降解血红素生成胆红素、亚铁及一氧化碳过程的限速酶,具有重要的抗炎功能,其启动子部位GT重复序列的多态性可使该基因表达的水平不同,重复序列较短者基因转录活性较高。目的:观察冠状动脉旁路移植术后炎性标记物白... 详细信息

背景:血红素氧化酶1是降解血红素生成胆红素、亚铁及一氧化碳过程的限速酶,具有重要的抗炎功能,其启动子部位GT重复序列的多态性可使该基因表达的水平不同,重复序列较短者基因转录活性较高。目的:观察冠状动脉旁路移植术后炎性标记物白细胞介素6,C-反应蛋白及纤维蛋白原的水平及其相关性,探讨血红素氧化酶1基因变量对它们的影响。设计、时间及地点:观察性试验,于2003年在英国伦敦大学学院心血管遗传病学中心完成。对象:220例符合入选条件的行冠状动脉旁路移植术的患者,男179例,女41例,年龄(63.34±9.64)岁。方法:PCR方法和DNA测序仪分析其血红素氧化酶1基因启动子部位GT重复序列的长短;于手术前及术后6,24,48,72,96,120h分别测白细胞介素6、C-反应蛋白和纤维蛋白原水平。主要观察指标:血红素氧化酶1基因启动子部位GT重复序列的长短;手术前及术后不同时间白细胞介素6、C-反应蛋白和纤维蛋白原水平。结果:术前白细胞介素6水平与C-反应蛋白及纤维蛋白原值显著相关(r=0.48,P<0.0001;r=0.41,P<0.0001),术后3者均显著升高,白细胞介素6峰质量浓度与C-反应蛋白峰质量浓度显著相关(r=0.34,P=0.0009),但与纤维蛋白原峰值无明显相关性(r=0.15,P=0.13)。术前C-反应蛋白值在血红素氧化酶1各基因组间存在明显差异,长GT重复序列者比短GT重复序列携带者高[(3.76±0.79),(2.07±0.17)mg/L,P=0.013];术后则各基因型组间水平相似。结论:炎症标志物的水平间存在相关性,血红素氧化酶1基因多态只与术前的基础C-反应蛋白和纤维蛋白原值有关,提示其可能只影响疾病的慢性炎症状态,从而影响炎性疾病的发生,而非急性炎症反应。

关键词：血红素氧化酶1 基因多态炎症反应冠状动脉旁路移植术

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气候变化：医务人员面临的挑战--以某种方式传递负面消息以激发正面响应

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英国医学杂志中文版 2014年第1期17卷 6-7页

作者： Anthony Costello hugh montgomery Nick Watts 周平(译) Institute for Clobal Health University College London WC1N 1EHUK 中国医学科学院医学信息研究所

政府问气候变化专门委员会（Intergovernmental Panel on Climate Change）得出的主要结论令人堪忧，忧虑的不仅在于环境问题，而且在于公共健康问题。全球变暖是显而易见的，且自20世纪50年代开始，我们观察到了过去数十年，甚至数千... 详细信息

政府问气候变化专门委员会（Intergovernmental Panel on Climate Change）得出的主要结论令人堪忧，忧虑的不仅在于环境问题，而且在于公共健康问题。全球变暖是显而易见的，且自20世纪50年代开始，我们观察到了过去数十年，甚至数千年来都从未出现过的气候变化。

关键词：气候变化医务人员激发消息传递环境问题健康问题全球变暖

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冠状动脉旁路术后的炎症反应:血红素氧化酶-1基因多态的影响

冠状动脉旁路术后的炎症反应:血红素氧化酶-1基因多态的影响

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中华医学会心血管病分会第八次全国心血管病学术会议

作者：李萍 Jules Sanders Emma Hawe Jutta Palmen David Brull Sukhbir Dhamrait Jayshree Acharya hugh montgomery Steve Humphries 江医二附院心内科 Centre for Cardiovascular Genetics BHF laboratories University College London

目的血红素氧化酶-1(HO-1)是降解血红素生成胆红素、亚铁及一氧化碳过程的限速酶,具有重要的抗炎功能,其启动子部位GT重复序列的多态性可使该基因表达的水平不同,重复序列较短者基因转录活性较高。本研究观察冠状动脉旁路术(CABG)后炎...

目的血红素氧化酶-1(HO-1)是降解血红素生成胆红素、亚铁及一氧化碳过程的限速酶,具有重要的抗炎功能,其启动子部位GT重复序列的多态性可使该基因表达的水平不同,重复序列较短者基因转录活性较高。本研究观察冠状动脉旁路术(CABG)后炎性标记物白介素6(IL-6),C反应蛋白(CRP)及纤维蛋白原(fibrinogen,Fb)的水平及其相关性,并探讨基因变量对它们的影响。方法220名符合入选条件的行CABG术的患者,用PCR方法和DNA测序仪分析他们HO-1基因启动子部位GT重复序列的长短;于手术前及术后6、24、48、72、96和120小时分别测IL-6、CRP和Fb值。结果术前IL-6水平与CRP及Fb值明显相关(分别为(r=0.48,P<0.0001;r=0.41,P<0.0001),术后三者均显著升高,IL-6峰浓度与CRP峰浓度有很强的相关性(r=0.34,P=0.0009),但与Fb峰值相关性欠佳(r=0.15,P=0.13)。术前CRP值在HO-1各基因组间存在明显差异,长GT重复序列者CRP值比短GT重复序列携带者高(3.76±0.79比2.07±0.17,P=0.013);术后则各基因型组间水平相似。结论炎症标志物的水平间存在相关性,HO-1基因多态只与术前的基础CRP和Fb值有关,提示它可能只影响疾病过程的慢性炎症状态,从而可能影响炎性疾病的发生,而非急性炎症反应。

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冠脉旁路搭桥术后的炎症反应:HO-1基因多态的影响

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介入放射学杂志 2003年第S1期12卷 169-页

作者：李萍 Jules Sanders Emma Hawe Jutta Palmen David Brull Sukhbir Dhamrait Jayshree Acharya hugh montgomery Steve Humphries 江西医学院第二附属医院心内科 330006

目的　观察冠状动脉旁路 (CABG)手术为刺激手段 ,研究术后炎性标记物白介素 6 (IL 6 ) ,C反应蛋白 (CRP)及纤维蛋白原 (fibrinogen ,Fb)的水平及其相关性 ,并探讨基因变量对它们的影响。方法　 2 2 0名符合入选条件的行CABG术的患者 ,用... 详细信息

目的　观察冠状动脉旁路 (CABG)手术为刺激手段 ,研究术后炎性标记物白介素 6 (IL 6 ) ,C反应蛋白 (CRP)及纤维蛋白原 (fibrinogen ,Fb)的水平及其相关性 ,并探讨基因变量对它们的影响。方法　 2 2 0名符合入选条件的行CABG术的患者 ,用PCR和DNA测序仪分析其HO 1基因启动子部位GT重复序列的长短 ;于手术前及术后 6 ,2 4 ,4 8,72 ,96和 12 0h分别测IL 6 ,CRP和Fb值。结果　术前CRP及Fb值与IL 6水平明显相关 (分别为r =0 .4 8,P <0 .0 0 0 1;r =0 .4 1,P <0 .0 0 0 1) ,术前三者均显著升高 ,CRP峰浓度与IL 6峰浓度有很强的相关性 (r =0 .34,P =0 .0 0 0 9) ,但后者的Fb峰值无关 (r=0 .15 ,P =0 .13)。基础CRP值在HO 1各基因组间存在明显差异 ,携带较长GT重复序列者较之非长GT重复序列携带者 ,CRP值较高 (3.76± 0 .79和 2 .0 7± 0 .17,P =0 .0 13) ;术后则各基因型组间水平相似。结论　炎症标志物的水平间存在相关性 ,HO 1基因多态只与术前基础的CRP和Fb值有关 ,提示它可能只影响疾病过程的慢性炎症状态 ,从而可能影响炎性疾病的发生 ,而非急性炎症反应。

关键词： CRP 术前 HO-1 基因多态 CABG

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Finite element analysis of small-scale hot compression testing

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Journal of Materials Science & Technology 2021年第17期76卷 174-188页

作者： Patryk Jedrasiak hugh Shercliff Department of Engineering University of CambridgeTrumpington StCambridgeCB21PZUK

This paper models hot compression testing using a dilatometer in loading *** small-scale tests provide a high throughput at low cost,but are susceptible to inhomogeneity due to friction and temperature gradients.A novel method is presented for correcting the true stress-strain constitutive response over the full range of temperatures,strain-rates and *** nominal response from the tests is used to predict the offset in the stress-strain curves due to inhomogeneity,and this stress offsetΔσis applied piecewise to the data,correcting the constitutive response in one iteration.A key new feature is the smoothing and fitting of the flow stress data as a function of temperature and strain-rate,at multiple discrete *** corrected model then provides quantitative prediction of the spatial and temporal variation in strain-rate and strain throughout the sample,needed to correlate the local deformation conditions with the microstructure and texture *** study uses a detailed series of 144 hot compression tests of a Zr-Nb *** this is an important wrought nuclear alloy in its own right,it also serves here as a test case for modelling the dilatometer for hot testing of high temperature alloys,particularly those with dualα-βphase microstructures(such as titanium alloys).

关键词： Finite element analysis Process modelling Hot compression testing Upsetting Zr alloys Ti alloys

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Stress-augmented thermal activation:Tribology feels the force

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Friction 2018年第1期6卷 1-31页

作者： hugh SPIKES Tribology Group Department of Mechanical EngineeringImperial College

In stress-augmented thermal activation, the activation energy barrier that controls the rate of atomic and molecular processes is reduced by the application of stress, with the result that the rate of these processes increases exponentially with applied stress. This concept has particular relevance to Tribology, and since its development in the early twentieth century, it has been applied to develop important models of plastic flow, sliding friction, rheology, wear, and tribochemistry. This paper reviews the development of stress-augmented thermal activation and its application to all of these areas of Tribology. The strengths and limitations of the approach are then discussed and future directions considered. From the scientific point of view, the concept of stress-augmented thermal activation is important since it enables the development of models that describe macroscale tribological performance, such as friction coefficient or tribofilm formation, in terms of the structure and behaviour of individual atoms and molecules. This both helps us understand these processes at a fundamental level and also provides tools for the informed design of lubricants and surfaces.

关键词： stress activation stress augmented thermal activation mechanochemistry friction EHD friction wear Eyring

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Masirah-the other Oman ophiolite:A better analogue for mid-ocean ridge processes?

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Geoscience Frontiers 2017年第6期8卷 1253-1262页

作者： hugh Rollinson Geoscience University of DerbyKedleston RoadDerby DE22 1GBUK

Oman has two ophiolites-the better known late Cretaceous northern Oman(or Semail)ophiolite and the lesser known and smaller,Jurassic Masirah ophiolite located on the eastern coast of the country adjacent to the Indian Ocean.A number of geological,geochronological and geochemical lines of evidence strongly suggest that the northern Oman ophiolite did not form at a mid-ocean ridge but rather in a supra-subduction zone setting by fast spreading during subduction *** contrast the Masirah ophiolite is structurally part of a series of ophiolite nappes which are rooted in the Indian Ocean *** are significant geochemical differences between the Masirah and northern Oman ophiolites and none of the supra-subduction features typical of the northern Oman ophiolite are found at *** Masirah is MORB,although in detail it contains both enriched and depleted MORB reflecting a complex source for the lavas and *** enrichment of this source predates the formation of the *** condensed crustal section on Masirah(ca.2 km)contains a very thin gabbro sequence and is thought to reflect its genesis from a cool mantle source associated with the early stages of sea-floor spreading during the early separation of eastern and western *** data suggest that the Masirah ophiolite is a suitable analogue for an ophiolite created at a mid-ocean ridge,whereas the northern Oman ophiolite is *** stratigraphic history of the Masirah ophiolite shows that it remained a part of the oceanic crust for ca.80 *** chemical variability and enrichment of the Masirah lavas is similar to that found elsewhere in Indian Ocean basalts and may simply reflect a similar provenance rather than a feature fundamental to the formation of the ophiolite.

关键词： Oman Ophiolite Suprasubduction Sea-floor spreading Masirah

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Limitations in assessment of mucosal healing in inflammatory bowel disease

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World Journal of Gastroenterology 2010年第1期16卷 15-20页

作者： hugh James Freeman Department of Medicine University of British Columbia

An emerging parameter to define the effectiveness of new therapeutic agents in clinical trials,and by extension,for use in day-to-day clinical practice has been labeled mucosal *** has been hypothesized that complete healing of the intestinal mucosa in inflammatory bowel diseases should result in reduced disease complications,reduced hospitalization and reduced surgical *** implication,the natural history of inflammatory bowel disease might then be altered. Measurement of mucosal healing,however,is largely observational,requiring repeated invasive endoscopic examinations,sometimes with mucosal *** indirect imaging methods may play a role in this assessment along with other surrogate markers,including intestinal *** measurements may have significant limitations that prohibit precise correlation with symptom-based disease activity indices in clinical *** likely reflects the dynamic nature of this evolving and individualized inflammatory process that tends to be focused,but not limited,to the mucosa of the intestinal tract.

关键词： Intestinal mucosa Digestive system endoscopy Clinical trials

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Surveillance for colitis-associated colon neoplasia

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World Journal of Gastroenterology 2010年第37期16卷 4646-4651页

作者： hugh James Freeman Department of Medicine University of British Columbia

The risk of developing colon cancer is increased in colitis patients, particularly if the disease is extensive and its duration long-standing. Endoscopic guidelines have been developed with the goal of detecting early neoplastic changes prior to development of advanced malignancy. Unfortunately, the natural history of this superimposed neoplastic process in colitis appears to be very heterogeneous and poorly understood. Moreover, there are numerous confounding variables in colitis patients that limit accurate assessment of the surveillance effectiveness of colonoscopy and multi-site biopsy protocols. Although the clinical challenge posed to even the most experienced clinicians remains significant, evolving methods of endoscopic imaging may facilitate better evaluation of this highly select group of patients.

关键词： Ulcerative colitis Crohn’s disease Colon cancer Surveillance colonoscopy Colon biopsies

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