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| 1 | Biochemical mechanisms in drug-induced liver injury:Certainties and doubts显示文摘Drug-induced liver injury is a significant and still unresolved clinical problem.Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development.Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites.Aging,preexisting liver disease,enzyme induction or inhibition,genetic variances,local O2 supply and,above all,the intrinsic molecular properties of the drug may affect this process.Necrotic death follows antioxidant consumption and oxidation of intracellular proteins,which determine increased permeability of mitochondrial membranes,loss of potential,decreased ATP synthesis,inhibition of Ca2+-dependent ATPase,reduced capability to sequester Ca2+ within mitochondria,and membrane bleb formation.Conversely,activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis.Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage.Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis,in which different HLA genotypes might play a major role.This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage.Future perspectives including new frontiers for research are discussed. | Ignazio Grattagliano Leonilde Bonfrate Catia V Diogo Helen H Wang David QH Wang Piero Portincasa | 2009 | World Journal of Gastroenterology2009，15，39： | 30 |
| 2 | Counter-regulatory phosphatases TNAP and NPP1 temporally regulate tooth root cementogenesis显示文摘Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone.Biomineralization is regulated by the ratio of inorganic phosphate(Pi) to mineral inhibitor pyrophosphate(PPi), where local Piand PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase(TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1(NPP1). The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enpp1 null mouse increased acellular cementum, with little effect on cellular cementum.Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enpp1 gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPienvironment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPihave little effect on cellular cementum formation, though matrix mineralization is affected. | Laura E Zweifler Mudita K Patel Francisco H Nociti Jr Helen F Wimer Jose L Milln Martha J Somerman Brian L Foster | 2015 | International Journal of Oral Science2015，7，1： | 5 |
| 3 | 黄土丘陵区洞穴侵蚀产流产沙规律初步研究显示文摘通过对黄土丘陵沟壑区羊道沟试验区 6个洞穴系统连续两年共11场暴雨产流产沙资料的分析,认为黄土丘陵沟壑区洞穴侵蚀的重点是梯田、缓坡地和植被覆盖较好的地方。同时初步揭示了该区洞穴侵蚀的产流产沙规律。 | 朱同新 蔡强国 高平 魏中平 Luk S H Tayor Helen | 1992 | 水土保持学报1992，6，1： | 4 |
| 4 | Chronic overexpression of PNPLA3^sup I148M^ in mouse liver causes hepatic steatosis显示文摘 | Li John Zhong Huang Yongcheng Karaman Ruchan Ivanova Pavlina T Brown H Alex Roddy Thomas Castro-Perez Jose Cohen Jonathan C Hobbs Helen H | 2012 | EN2012，，11： | 3 |
| 5 | Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial显示文摘 | A David Mendelow Barbara A Gregson Helen M Fernandes Gordon D Murray Graham M Teasdale D Terence Hope Abbas Karimi M Donald M Shaw David H Barer | 2005 | 2005 (9457)2005，，9457： | 2 |
| 6 | Antipsychotic Medications in Major Depression and the Association with Treatment Satisfaction and Quality of Life: Findings of Three National Surveys on Use of Psychotropics in China Between 2002 and 2012显示文摘 | Yu-Xi Wang Yu-Tao Xiang Yun-Ai Su Qian Li Liang Shu Chee H Ng Gabor S Ungvari Helen FK Chiu Yu-Ping Nin Gao-Hua Wang Pei-Shen Bai Tao Li Li-Zhong Sun Jian-Guo Shi Xian-Sheng Chen Qi-Yi Mei Ke-Qing Li Xin Yu Tian-Mei Si | 2015 | Chinese Medical Journal2015，，14： | 2 |
| 7 | The economic implications of using HACCP as a food safety regulatory standard显示文摘 | Laurian J Unnevehr Helen H Jensen | 1999 | Food Policy1999，，6： | 2 |
| 8 | Codon usage and gene function are related in sequences of Arabidopsis thaliana 显示文摘 | Helene C Fred6rique L Michel C Alain H | 1998 | Gene1998，209，： | 1 |
| 9 | Silk-based biomaterials显示文摘 | Gregory H Altman Frank Diaz Caroline Jakuba Tara Calabro Rebecca L Horan Jingsong Chen Helen Lu John Richmond David L Kaplan | 2002 | Biomaterials2002，，3： | 1 |
| 10 | Nonuniformity of fetal umbilical systolic/diastotic ratios as determined with duplex Doppler sonography显示文摘 | HELEN H K | 1989 | J Ultrasound Med1989，8，8： | 1 |
| 11 | Multiphase hydrodynamics and solid-liquid mass transport in an external-loop airlift reactor-a comparative study显示文摘 | Mao Helen H H Chisti Y Moo-Young M | 1992 | Chem Eng Commun1992，113，： | 1 |
| 12 | Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial显示文摘 | A David Mendelow Barbara A Gregson Helen M Fernandes Gordon D Murray Graham M Teasdale D Terence Hope Abbas Karimi M Donald M Shaw David H Barer | 2005 | The Lancet2005，，9457： | 1 |
| 13 | Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial显示文摘 | Helen M Colhoun D John Betteridge Paul N Durrington Graham A Hitman H Andrew W Neil Shona J Livingstone Margaret J Thomason Michael I Mackness Valentine Charlton-Menys John H Fuller | 2004 | The Lancet . 2004 (9435)2004，，9435： | 1 |
| 14 | Measurement of specific Ig A in faecal extracts and intestinal lavage fluid for monitoring of mucosal immune responses显示文摘 | Harleen M S Tom H K Helene V | 2000 | J Immun Meth2000，239，6： | 1 |
| 15 | Somatostatin - like immunoreactivity in human sympathetic ganglia显示文摘 | Jarvi R Pelto H M Helen P | 1987 | Cell Tissue Res1987，249，1： | 1 |
| 16 | A Si BiCMOS transimpedance amplifier for 10 Gbit/s SONET receiver显示文摘 | Kim Helen H Chandrasekhar S Burrus Charles A | 2001 | IEEE Journal of Solid-State Circuits2001，36，5： | 1 |
| 17 | Phase Ⅱ studies of gemcitabine and cisplatin in heavily and minimally pretreated metastatic breast cancer显示文摘 | Helen K Chew James H | 2009 | J Clin 0ncol2009，27，13： | 1 |
| 18 | Cryopreserved-thawedembryo transfer in natural or down-regulated hormonallycontrolled cycles: aretrospectivestudy 显示文摘 | Tarek G Luciano N Helen H | 2006 | Fertil Steril2006，85，3： | 1 |
| 19 | Physiological responses of cabbage to incipient copper toxicity显示文摘 | Penelope A R Helen C H Kenneth L S | 1989 | J Amer Soc Hor Sci1989，114，1： | 1 |
| 20 | Current status of dry and quasi-dry processes for pollutant separation from waste incineration plants and power stations 显示文摘 | Mayer-Schwinning G Helen H | 1995 | Environment Solution1995，32，2： | 1 |
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