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| 1 | No association between cyclooxygenase-2 and uridine diphosphate glucuronosyltransferase 1A6 genetic polymorphisms and colon cancer risk显示文摘AIM:To investigate the association of variations in the cyclooxygenase-2(COX2) and uridine diphosphate glucuronosyltransferase 1A6(UGT1A6) genes and non-steroidal anti-inflammatory drugs(NSAIDs) use with risk of colon cancer.METHODS:NSAIDs,which are known to reduce the risk of colon cancer,act directly on COX2 and reduce its activity.Epidemiological studies have associated variations in the COX2 gene with colon cancer risk,but others were unable to replicate this finding.Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas.Polymorphisms in the UGT1A6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas,but not colon cancer.Here we examined the association of tagging single nucleotide polymorphisms(SNPs) in the COX2 and UGT1A6 genes,and their interaction with NSAID consumption,on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.RESULTS:No SNP in either gene was individually statistically significantly associated with colon cancer,nor did they statistically significantly change the protective effect of NSAID consumption in our sample.Like others,we were unable to replicate the association of variants in the COX2 gene with colon cancer risk(P > 0.05),and we did not observe that these variants modify the protective effect of NSAIDs(P > 0.05).We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk,although further studies will have to be conducted to confirm the association of these variants with colon adenomas.CONCLUSION:Our study does not support a role of COX2 and UGT1A6 genetic variations in the development of colon cancer. | Cheryl L Thompson Sarah J Plummer Alona Merkulova Iona Cheng Thomas C Tucker Graham Casey Li Li | 2009 | World Journal of Gastroenterology2009，15，18： | 11 |
| 2 | Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy显示文摘AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell(PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor(TLR) expression and cytokine production post TLR stimulation was assessed in UC 'responders'(n = 12) and 'non-responders'(n = 12) and compared to healthy controls(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory(TNF, IL-1β, IL-6), immuno-regulatory(IL-10), Th1(IL-12, IFNγ) and Th2(IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS.RESULTS Prior to anti-TNF therapy, responders and nonresponders had similar level of disease severity and activity. PBMC's ability to respond to TLR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders(P < 0.05). Following TLR stimulation, nonresponders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls(P < 0.01) and diminished TNF(P < 0.001) and IL-1β(P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells(p DCs)(P < 0.01) but increased number of CD4+ regulatory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2,-4 and-7 activation(P < 0.001). CONCLUSION Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy. | Angela C Baird Dominic Mallon Graham Radford-Smith Julien Boyer Thierry Piche Susan L Prescott Ian C Lawrance Meri K Tulic | 2016 | World Journal of Gastroenterology2016，22，41： | 10 |
| 3 | H2O2-Activated Up-Regulation of Glutathione in Arabidopsis Involves Induction of Genes Encoding Enzymes Involved in Cysteine Synthesis in the Chloroplast显示文摘谷胱甘肽在对 H2O2 的反应是在细胞的氧化还原作用动态平衡并且,因此的一个关键播放器,但是调整激活氧化的谷胱甘肽合成的因素仍然是不清楚的。我们在有条件的 Arabidopsis 过氧化氢酶缺乏的异种(cat2 ) 调查了导致 H2O2 的谷胱甘肽合成。植物为 5 在提高的 CO2 从种子被种 ? 星期,然后处于短天或长天的条件转了到空气。处于任何条件在提高的 CO2 或野类型的植物比作 cat2,到在两个光周期的空气的 cat2 的转移在小时以内引起了叶谷胱甘肽水池的可测量的氧化。氧化在随后的天继续并且被谷胱甘肽的累积伴随。这效果在在短天内转移到空气的 cat2 是更强壮的,并且没被连接到可引出的活动或涉及谷胱甘肽合成的承诺的小径的抄本编码酶的可估计的增加。相反,它被丝氨酸, O-acetylserine,和半胱氨酸的增加伴随。在代谢物的这些变化被编码腺苷 phosphosulfate reductase (4 月) 的基因的正式就职伴随,特别地, APR3,以及编码 chloroplastic 的特定的丝氨酸 acetyltransferase 基因(SAT2.1 ) 坐了。标记这些基因的正式就职仅仅在处于短天的条件转移到空气的 cat2 被观察,在半胱氨酸和谷胱甘肽累积是很戏剧的的地方。不同于另外的容纳的基因,它在 cat2 显示出可以忽略的正式就职,相对许多 4 月和 SAT2.1 抄本密切为 H2O2 发信号与标记抄本被相关。一起,数据在谷胱甘肽合成的导致氧化剂的起来规定加重半胱氨酸合成的重要性并且建议叶绿体在这些情形下面做重要贡献到半胱氨酸生产。 | Guillaume Queval Dorothée Thominet Hélène Vanacker Myroslawa Miginiac-Maslow Bertrand Gakière Graham Noctor | 2009 | Molecular Plant2009，2，2： | 10 |
| 4 | Dementia and osteoporosis in a geriatric population: Is there a common link?显示文摘AIM To determine the existence of a common pathological link between dementia and osteoporosis through reviewing the current evidence base. METHODS This paper reviews the current literature on osteoporosis and dementia in order to ascertain evidence of a common predisposing aetiology. A literature search of Ovid MEDLINE(1950 to June 2016) was conducted. The keywords 'osteoporosis', 'osteoporotic fracture', 'dementia' and 'Alzheimer's disease'(AD) were used to determine the theoretical links with the most significant evidence base behind them. The key links were found to be vitamins D and K, calcium, thyroid disease, statins, alcohol and sex steroids. These subjects were then searched in combination with the previous terms and the resulting papers manually examined. Theoretical, in vitro and in vivo research were all used to inform this review which focuses on the most well developed theoretical common causes for dementia(predominantly Alzheimer's type) and osteoporosis.RESULTS Dementia and osteoporosis are multifaceted disease processes with similar epidemiology and a marked increase in prevalence in elderly populations. The existence of a common link between the two has been suggested despite a lack of clear pathological overlap in our current understanding. Research to date has tended to be fragmented and relatively weak in nature with multiple confounding factors reflecting the difficulties of in vivo experimentation in the population of interest. Despite exploration of various possible mechanisms in search for a link between the two pathologies, this paper found that it is possible that these associations are coincidental due to the nature of the evidence available. One finding in this review is that prior investigation into common aetiologies has found raised amyloid beta peptide levels in osteoporotic bone tissue, with a hypothesis that amyloid beta disorders are systemic disorders resulting in differing tissue manifestations. However, our findings were that the most compelling evidence of a common yet independent aetiology lies in the APOE4 allele, which is a well-established risk for AD but also carries an independent association with fracture risk. The mechanism behind this is thought to be the reduced plasma vitamin K levels in individuals exhibiting the APOE4 allele which may be amplified by the nutritional deficiencies associated with dementia, which are known to include vitamins K and D. The vitamin theory postulates that malnutrition and reduced exposure to sunlight in patients with AD leads to vitamin deficiencies. CONCLUSION Robust evidence remains to be produced regarding potential links and regarding the exact aetiology of these diseases and remains relevant given the burden of dementia and osteoporosis in our ageing population. Future research into amyloid beta, APOE4 and vitamins K and D as the most promising aetiological links should be welcomed. | Candice L Downey Adam Young Emily F Burton Simon M Graham Robert J Macfarlane Eva-Maria Tsapakis Eleftherios Tsiridis | 2017 | World Journal of Orthopedics2017，8，5： | 6 |
| 5 | Optimization and approximation in deterministic sequencing and scheduling:A survey显示文摘 | Graham R L Lawler E L Lenstra J K | 1979 | Annals of Discrete Mathematics1979，5，： | 2 |
| 6 | Bounds on multiprocessing timing anomalies显示文摘 | Graham R L | 1969 | SIAM J Appl Math1969，17，： | 2 |
| 7 | No association between phosphatase and tensin homolog genetic polymorphisms and colon cancer显示文摘AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homolog (PTEN) tumor suppressor gene and risk of colon cancer. METHODS: We utilized a population-based casecontrol study of incident colon cancer individuals (n= 421) and controls (n = 483) aged ≥ 30 years to conduct a comprehensive tagSNP association analysis of the PTEN gene. RESULTS: None of the PTEN SNPs were statistically significantly associated with colon cancer when controlled for age, gender, and race, or when additionally adjusted for other known risk factors (P > 0.05). Haplotype analyses similarly showed no association between the PTEN gene and colon cancer. CONCLUSION: Our study does not support PTEN as a colon cancer susceptibility gene. | Lynette S Phillips Cheryl L Thompson Alona Merkulova Sarah J Plummer Thomas C Tucker Graham Case Li Li | 2009 | World Journal of Gastroenterology2009，15，30： | 2 |
| 8 | Ductility reduction factor in the seismic design of buildings 显示文摘 | NELSON L JOHN W GRAHAM H | 1998 | Earthquake Engineering & Structural Dynamics1998，27，7： | 2 |
| 9 | Reduced striatal volumes in Parkinson’s disease:a magnetic resonance imaging study显示文摘Background:The presence and extent of structural changes in the brain as a consequence of Parkinson’s disease(PD)is still poorly understood.Methods:High-resolution 3-tesla T1-weighted structural magnetic resonance images in sixty-five PD and 27 age-matched healthy control participants were examined.Putamen,caudate,and intracranial volumes were manually traced in the axial plane of 3D reconstructed images.Striatal nuclei volumes were normalized to intracranial volume for statistical comparison.Disease status was assessed using the Unified Parkinson’s Disease Rating Scale and Hoehn and Yahr scale.Cognitive status was assessed using global status tests and detailed neuropsychological testing.Results:Both caudate and putamen volumes were smaller in PD brains compared to controls after adjusting for age and gender.Caudate volumes were reduced by 11%(p=0.001)and putamen volumes by 8.1%(p=0.025).PD striatal volumes were not found to be significantly correlated with cognitive or motor decline.Conclusion:Small,but significant reductions in the volume of both the caudate and putamen occur in PD brains.These reductions are independent of the effects of age and gender,however the relation of these reductions to the functional loss of dopamine,which is characteristic of PD,remains unclear. | Toni L Pitcher Tracy R Melzer Michael R MacAskill Charlotte F Graham Leslie Livingston Ross J Keenan Richard Watts John C Dalrymple-Alford Tim J Anderson | 2012 | Translational Neurodegeneration2012，1，1： | 2 |
| 10 | Laboratory assessment of hepatic injury in the woodchuck (Marmota monax)显示文摘 | Hornbuckle W E Graham E S Roth L | 1985 | Lab Anim Sci1985，35，： | 1 |
| 11 | A new technique for the assay of infectivity of human adenovirus 5 DNA显示文摘 | van der Eb A J | 1973 | Virology1973，52，2： | 1 |
| 12 | On the theory of flashover development显示文摘 | Graham T L Makhviladze G Roberts J P | 1995 | Fire Safety Journal1995，25，： | 1 |
| 13 | New PDC bit design reduces vibrational problems显示文摘 | Graham M W Will L A | 1995 | Oil and Gas Journal1995，93，22： | 1 |
| 14 | The Cause of Decreased Pan Evaporation over the Past 50 Years显示文摘 | Michael L Roderick Graham D Farquhar | 2002 | Science2002，298，： | 1 |
| 15 | Optimization and approximation in deterministic sequencing and scheduling: A survey显示文摘 | Graham R L Lawler E L Lenstra J K | 1979 | Annals of Discrete Mathematics1979，5，： | 1 |
| 16 | New tricks for old trees: maps and the pigonhole principle显示文摘 | GRAHAM N ENTRINGER R C SZEKELY L A | 1994 | Amer Math Monthly1994，101，7： | 1 |
| 17 | Congenital malformation of the ear and cochear implantation in children:Review and Temporal bone report of common cavity显示文摘 | GRAHAM J M PHELPS P D MICHAELS L | 2000 | J Laryngol Otol Suppl2000，25，： | 1 |
| 18 | Long-distance growth and connec- tivity of neural stem cells after severe spinal cord injury 显示文摘 | Lu P Wang Y Graham L | 2012 | Cell2012，150，6： | 1 |
| 19 | The effect of sample size and species characteristics on performance of different species distribution modeling methods 显示文摘 | Hernandez P A Graham C H Master L L | 2006 | Ecography2006，29，5： | 1 |
| 20 | Detrital zir- con provenance of the Late Triassic Songpan Ganzi com- plex: Sedimentary record of collision of the North and South China blocks显示文摘 | Weislogel A L Graham S A Chang E Z | 2006 | Geology2006，34，2： | 1 |
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