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| 1 | Elevated blood pressure: Our family's fault?The genetics of essential hypertension显示文摘AIM: To provide an updated review on current genetic aspects possibly affecting essential hypertension(EH), and to further elucidate their role in EH. METHODS: We searched for genetic and epigenetic factors in major studies associated with EH between Jan 2008-Oct 2013 using PubMed. We limited our search to reviews that discussed mostly human studies, and were accessible through the university online re-source. We found 11 genome wide association studies(GWAS), as well as five methylation and three miRNA studies that fit our search criteria. A distinction was not made between genes with protective effects or nega-tive effects, as this article is only meant to be a sum-mary of genes associated with any aspect of EH.RESULTS: We found 130 genes from the studies that met our inclusion/exclusion criteria. Of note, genes withmultiple study references include: STK39, CYP17A1, MTHFR-NPPA, MTHFR-NPPB, ATP2B1, CSK, ZNF652, UMOD, CACNB2, PLEKHA7, SH2B3, TBX3-TBX5, ULK4, CSK-ULK3, CYP1A2, NT5C2, CYP171A, PLCD3, SH2B3, ATXN2, CACNB2, PLEKHA7, SH2B3, TBX3-TBX5, ULK4, and HFE. The following genes overlapped between the genetic studies and epigenetic studies: WNK4 and BDKRB2. Several of the identified genes were found to have functions associated with EH. Many epigenetic factors were also correlated with EH. Of the epigenetic factors, there were no articles discussing siRNA and its effects on EH that met the search criteria, thus the topic was not included in this review. Among the miRNA tar-gets found to be associated with EH, many of the genes involved were also identified in the GWAS studies.CONCLUSION: Genetic hypertension risk algorithms could be developed in the future but may be of limited benefit due to the multi-factorial nature of EH. With emerging technologies, like next-generation sequenc-ing, more direct causal relationships between genetic and epigenetic factors affecting EH will likely be discov-ered creating a tremendous potential for personalized medicine using pharmacogenomics. | Aniket Natekar Randi L Olds Meghann W Lau Kathleen Min Karra Imoto Thomas P Slavin | 2014 | World Journal of Cardiology2014，6，5： | 7 |
| 2 | Colonoscopy surveillance for high risk polyps does not always prevent colorectal cancer显示文摘AIM To determine the frequency and risk factors for colorectal cancer(CRC) development among individuals with resected advanced adenoma(AA)/traditional serrated adenoma(TSA)/advanced sessile serrated adenoma(ASSA). METHODS Data was collected from medical records of 14663 subjects found to have AA, TSA, or ASSA at screening or surveillance colonoscopy. Patients with inflammatory bowel disease or known genetic predisposition for CRC were excluded from the study. Factors associated with CRC developing after endoscopic management of high risk polyps were calculated in 4610 such patients who had at least one surveillance colonoscopy within 10 years following the original polypectomy of the incident advanced polyp. RESULTS84/4610(1.8%) patients developed CRC at the polypectomy site within a median of 4.2 years(mean 4.89 years), and 1.2%(54/4610) developed CRC in a region distinct from the AA/TSA/ASSA resection site within a median of 5.1 years(mean 6.67 years). Approximately, 30%(25/84) of patients who developed CRC at the AA/TSA/ASSA site and 27.8%(15/54) of patients who developed CRC at another site had colonoscopy at recommended surveillance intervals. Increasing age; polyp size; male sex; right-sided location; high degree of dysplasia; higher number of polyps resected; and piecemeal removal were associated with an increased risk for CRC developmentat the same site as the index polyp. Increasing age; right-sided location; higher number of polyps resected and sessile endoscopic appearance of the index AA/TSA/ASSA were significantly associated with an increased risk for CRC development at a different site. CONCLUSION Recognition that CRC may develop following AA/TSA/ASSA removal is one step toward improving our practice efficiency and preventing a portion of CRC related morbidity and mortality. | Mohamad A Mouchli Lidia Ouk Marianne R Scheitel Alisha P Chaudhry Donna Felmlee-Devine Diane E Grill Shahrooz Rashtak Panwen Wang Junwen Wang Rajeev Chaudhry Thomas C Smyrk Ann L Oberg Brooke R Druliner Lisa A Boardman | 2018 | World Journal of Gastroenterology2018，24，8： | 5 |
| 3 | Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial显示文摘 | David N Krag Stewart J Anderson Thomas B Julian Ann M Brown Seth P Harlow Joseph P Costantino Takamaru Ashikaga Donald L Weaver Eleftherios P Mamounas Lynne M Jalovec Thomas G Frazier R Dirk Noyes André Robidoux Hugh MC Scarth Norman Wolmark | 2010 | Lancet Oncology2010，，10： | 3 |
| 4 | Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS. | Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight | 2010 | Cellular & Molecular Immunology2010，7，3： | 3 |
| 5 | Macrophage secretory products induce an inflammatory phenotype in hepatocytes显示文摘AIM:To investigate the influence of macrophages on hepatocyte phenotype and function.METHODS:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression determined.The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)infection.RESULTS:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin(7.8±2.5-fold,P=0.045)and transforming growth factor(TGF)-β1(2.6±0.2-fold,P<0.001)and downregulation of epithelial cadherin(1.7±0.02-fold,P=0.017)mRNA expression.Microarray analysis revealed significant upregulation of lipocalin-2(17-fold,P <0.001)and pathways associated with inflammation,and substantial downregulation of pathways related to hepatocyte function.In patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA(F0 1.0 ±0.3,F1 2.2±0.2,F2 3.0±9.3,F3/4 4.0±0.8,P= 0.003)and protein expression(F1 1.0±0.5,F2 1.3± 0.4,F3/4 3.6±0.4,P=0.014)with increasing liver injury.High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase(MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-β1(2.9±0.2 vs 1.04±0.1,P<0.001) in macrophage-conditioned media treated HepG2 cells.In patients with chronic HCV infection,hepatic mRNA expression of CD163(F0 1.0±0.2,F1/2 2.8±0.3,F3/4 5.3±1.0,P=0.001)and MMP-9(F0 1.0±0.4,F1/2 2.8±0.3,F3/4 4.1±0.8,P=0.011)was significantly associated with increasing stage of fibrosis.CONCLUSION:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participate in liver injury. | Michelle Melino Victoria L Gadd Gene V Walker Richard Skoien Helen D Barrie Dinesh Jothimani Leigh Horsfall Alun Jones Matthew J Sweet Gethin P Thomas Andrew D Clouston Julie R Jonsson Elizabeth E Powell | 2012 | World Journal of Gastroenterology2012，18，15： | 3 |
| 6 | Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial显示文摘 | David N Krag Stewart J Anderson Thomas B Julian Ann M Brown Seth P Harlow Takamaru Ashikaga Donald L Weaver Barbara J Miller Lynne M Jalovec Thomas G Frazier R Dirk Noyes André Robidoux Hugh MC Scarth Denise M Mammolito David R McCready Eleftherios P Mamo | 2007 | Lancet Oncology2007，，10： | 2 |
| 7 | Empagliflozin alleviates podocytopathy and enhances glomerular nephrin expression in db/db diabetic mice显示文摘BACKGROUND Modern guidelines recommend sodium-glucose cotransporter-2(SGLT2)inhibitors as the preferred antihyperglycemic agents for patients with type 2 diabetes and chronic kidney disease.However,the mechanisms underlying the renal protective effect of SGLT2 inhibitors are not fully understood.structure of podocytes and nephrin expression in glomeruli in db/db diabetic mice.METHODS We treated 8-wk-old male db/db mice with EMPA(10 mg/kg/d)or vehicle for 8 wk.Age-matched male db/+mice were included as non-diabetic controls.Parameters of body composition,glycemic and lipid control,and plasma concentrations of leptin,insulin and glucagon were assessed.We evaluated renal hypertrophy as kidney weight adjusted to lean mass,renal function as plasma levels of creatinine,and albuminuria as the urinary albumin-to-creatinine ratio(UACR).Renal structures were studied by light and transmission electron microscopy with a focus on mesangial volume and podocyte structure,respectively.Glomerular nephrin and transforming growth factor beta(TGF-β)were assessed by immunohistochemistry.RESULTS Severe obesity and hyperglycemia developed in db/db mice prior to the start of the experiment;increased plasma concentrations of fructosamine,glycated albumin,cholesterol,leptin,and insulin,and elevated UACR were detected.Mesangial expansion,glomerular basement membrane thickening,and increased area of TGF-βstaining in glomeruli were revealed in vehicle-treated mice.Podocytopathy was manifested by effacement of foot processes;nephrin-positive areas in glomeruli were reduced.EMPA decreased the levels of glucose,fructosamine and glycated albumin,UACR,kidney hypertrophy,mesangial expansion,glomerular basement membrane thickening,and glomerular TGF-βstaining,alleviated podocytopathy and restored glomerular staining of nephrin.CONCLUSION These data indicate that EMPA attenuates podocytopathy in experimental diabetic kidney disease.The anti-albuminuric effect of EMPA could be attributed to mitigation of podocyte injury and enhancement of nephrin expression. | Vadim V Klimontov Anton I Korbut Iuliia S Taskaeva Nataliya P Bgatova Maksim V Dashkin Nikolai BOrlov Anna S Khotskina Evgenii L Zavyalov Thomas Klein | 2020 | World Journal of Diabetes2020，11，12： | 2 |
| 8 | The effect of decoupled low-level flow on winter orographic clouds and precipitation in the Yampa River Valley显示文摘 | Thomas C P L O Grant W R Cotton | 1991 | J Appl Meteor1991，30，3： | 1 |
| 9 | Effective primary isolation of wild-type canine distemper virus in MDCK,MV1 Lu and Vero cells without nucleotide sequence changes within the entire haemagglutinin protein gene and in subgenomic sections of the fusion and phospho protein genes显示文摘 | John A L Thomas P M Michael J K | 2004 | Virology2004，118，： | 1 |
| 10 | Organic chemistry on a polyimide surface显示文摘 | Thomas R R Buchwalter S L Buchwalter L P | 1992 | Macromolecules1992，25，： | 1 |
| 11 | Genetic variation in IL28B and spontaneous clearance of hepatitis C virus 显示文摘 | Thomas D L Thio C L Martin M P | 2009 | Nature2009，461，： | 1 |
| 12 | Gold and trace element zonation in pyrite using a laser imaging technique: Implications for the timing of gold in orogenic and Carlin- style sediment- hosted deposits 显示文摘 | R R Large L Danyushevsky C Hollit V Maslennikov S Meffer S Gilbert S Bull R Scott P Emsbo H Thomas B Singh J Foster | 2009 | Economic Geology2009，104，5： | 1 |
| 13 | Invasive Pneumococcal Disease in Children 5 Years After Conjugate Vaccine Introduction - Eight States, 1998-2005显示文摘 | Reingold A Hadler J Farley M M Harrison L Lynfield R Lexau C Bennett N Thomas A Craig A S Smith P J Beall B Whitney C G Moore M Pilishvili T | 2008 | MMWR Morbidity and Mortality Weekly Report2008，，6： | 1 |
| 14 | Robust analysis of the yeast proteome under 50 kDa by molecular-massbased fractionation and top-down mass spectrometry显示文摘 | Kellie J F Catherman A D Durbin K R Tran J C Tipton J D Norris J L Witkowski C E 2nd Thomas P M Kelleher N L | | 0，，01： | 1 |
| 15 | Using fractal dimensions for characterizing intra-urban diversity: The example of Brussels 显示文摘 | Keersmaeeker M L D Frankhauser P Thomas I | 2003 | Geographical Analysis2003，35，4： | 1 |
| 16 | Marketing in hypermedia computer-mediated environments: con- ceptual foundations 显示文摘 | Hoffman Donna L Novak Thomas P | 1996 | Journal of Marketing1996，60，3： | 1 |
| 17 | Challenges in the as- sociation of human single nucleotide polymorphism mentions with unique database identifiers 显示文摘 | Thomas P Klinger R Furlong L | 2011 | BMC Bioinformatics2011，12，4： | 1 |
| 18 | Cell culture models of trophoblast II:trophoblast cell lines--a workshop report显示文摘 | King A Thomas L Bischof P | | 0，，： | 1 |
| 19 | Identification of polymorphic outer membrane protein of Chlamydia psittaic 6BC 显示文摘 | Regina J T David L Thomas P H | 2001 | Infect and Immun2001，69，： | 1 |
| 20 | Petrotoga mexicana sp nov,a novel thermophilic anaerobic and xylanolytic bacterium isolated from an oil-producing well in the Gulf of Mexico显示文摘 | Miranda-Tello E Fardtau M L Thomas P | 2004 | Int J Syst Evol Microbiol2004，54，1： | 1 |
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