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| 1 | Contractile apparatus dysfunction early in the pathophysiology of diabetic cardiomyopathy显示文摘Diabetes mellitus significantly increases the risk of cardiovascular disease and heart failure in patients.Independent of hypertension and coronary artery disease,diabetes is associated with a specific cardiomyopathy,known as diabetic cardiomyopathy(DCM).Four decades of research in experimental animal models and advances in clinical imaging techniques suggest that DCM is a progressive disease,beginning early after the onset of type 1 and type 2 diabetes,ahead of left ventricular remodeling and overt diastolic dysfunction.Although the molecular pathogenesis of early DCM still remains largely unclear,activation of protein kinase C appears to be central in driving the oxidative stress dependent and independent pathways in the development of contractile dysfunction.Multiple subcellular alterations to the cardiomyocyte are now being highlighted as critical events in the early changes to the rate of force development,relaxation and stability under pathophysiological stresses.These changes include perturbed calcium handling,suppressed activity of aerobic energy producing enzymes,altered transcriptional and posttranslational modification of membrane and sarcomeric cytoskeletal proteins,reduced actin-myosin cross-bridge cycling and dynamics,and changed myofilament calcium sensitivity.In this review,we will present and discuss novel aspects of the molecular pathogenesis of early DCM,with a special focus on the sarcomeric contractile apparatus. | Mark T Waddingham Amanda J Edgley Hirotsugu Tsuchimochi Darren J Kelly Mikiyasu Shirai James T Pearson | 2015 | World Journal of Diabetes2015，6，7： | 10 |
| 2 | Radiation exposure and reduction in the operating room: Perspectives and future directions in spine surgery显示文摘Intraoperative imaging is vital for accurate placement of instrumentation in spine surgery. However, the use of biplanar fluoroscopy and other intraoperative imaging modalities is associated with the risk of significant radiation exposure in the patient, surgeon, and surgical staff. Radiation exposure in the form of ionizing radiation can lead to cellular damage via the induction of DNA lesions and the production of reactive oxygen species. These effects often result in cell death or genomic instability, leading to various radiation-associated pathologies including an increased risk of malignancy. In attempts to reduce radiation-associated health risks, radiation safety has become an important topic in the medical field. All practitioners, regardless of practice setting, can practice radiation safety techniques including shielding and distance to reduce radiation exposure. Additionally, optimization of fluoroscopic settings and techniques can be used as an effective method of radiation dose reduction. New imaging modalities and spinal navigation systems have also been developed in an effort to replace conventional fluoroscopy and reduce radiation doses. These modalities include Isocentric Three-Dimensional C-Arms, O-Arms, and intraoperative magnetic resonance imaging. While this influx of new technology has advanced radiation safety within the field of spine surgery, more work is still required to overcome specific limitations involving increased costs and inadequate training. | Ankur S Narain Fady Y Hijji Kelly H Yom Krishna T Kudaravalli Brittany E Haws Kern Singh | 2017 | World Journal of Orthopedics2017，8，7： | 9 |
| 3 | Hematopoietic stem cell-derived adipocytes and fibroblasts in the tumor microenvironment显示文摘The tumor microenvironment(TME) is complex and constantly evolving. This is due, in part, to the crosstalk between tumor cells and the multiple cell types that comprise the TME, which results in a heterogeneous population of tumor cells and TME cells. This review will focus on two stromal cell types, the cancerassociated adipocyte(CAA) and the cancer-associated fibroblast(CAF). In the clinic, the presence of CAAs and CAFs in the TME translates to poor prognosis in multiple tumor types. CAAs and CAFs have an activated phenotype and produce growth factors, inflammatory factors, cytokines, chemokines, extracellular matrix components, and proteases in an accelerated and aberrant fashion. Through this activated state, CAAs and CAFs remodel the TME, thereby driving all aspects of tumor progression, including tumor growth and survival, chemoresistance, tumor vascularization, tumor invasion, and tumor cell metastasis. Similarities in the tumorpromoting functions of CAAs and CAFs suggest that a multipronged therapeutic approach may be necessary to achieve maximal impact on disease. While CAAs and CAFs are thought to arise from tissues adjacent to the tumor, multiple alternative origins for CAAs and CAFs have recently been identified. Recent studies from our lab and others suggest that the hematopoietic stem cell, through the myeloid lineage, may serve as a progenitor for CAAs and CAFs. We hypothesize that the multiple origins of CAAs and CAFs may contribute to the heterogeneity seen in the TME. Thus, a better understanding of the origin of CAAs and CAFs, how this origin impacts their functions in the TME, and thetemporal participation of uniquely originating TME cells may lead to novel or improved anti-tumor therapeutics. | Ying Xiong Lindsay T Mc Donald Dayvia L Russell Ryan R Kelly Katie R Wilson Meenal Mehrotra Adam C Soloff Amanda C LaRue | 2015 | World Journal of Stem Cells2015，7，2： | 6 |
| 4 | Randomized controlled trials - mechanistic studies of testosterone and the cardiovascular system显示文摘睾丸激素缺乏是普通的在里面有心血管的疾病( CVD )的人,和使随机化的控制安慰剂的试用( RCT )在长期的稳定的咽峡炎在导致锻练的心脏的局部缺血上报导了睾丸激素治疗的有益的效果,功能的锻练能力,最大的氧消费在锻练期间(在长期的心失败( CHF )的 VO 2max)和肌肉力量,一些心血管的风险因素的 Q-T 间隔,和改进弄短。睾丸激素缺乏与不利 CV 风险侧面和死亡被联系。临床、科学的研究提供了机械学的证据支持并且解释 RCT 的调查结果。睾丸激素包括肺的 vasculature 是在冠的发行量和另外的脉管的床以内的快速发作的动脉的血管扩张药并且能减少全面外部全身的脉管的抵抗。证据证明了那睾丸激素调停通过钙隧道封锁(L 钙隧道) 的脉管的反应上的这效果并且刺激钾隧道由直接 nongenomic 机制开。睾丸激素也由刺激超速的钾刺激心脏的 myocytes 的极化操作隧道的电流。睾丸激素改进心脏的输出,功能的锻练能力, VO 2max 和 vagally 调停的动脉的 baroreceptor 在 CHF 的心脏的反射敏感,和另外的机制。独立于心脏的功能上的睾丸激素的利益,睾丸激素替换可以也增加骨胳的肌肉葡萄糖新陈代谢并且提高肌肉发达的力量,能在能力可以包括的功能的锻练贡献改进的两个因素改进了葡萄糖新陈代谢和肌肉力量。睾丸激素由在关键新陈代谢的小径的规章的酶上由 genomic 的联合和葡萄糖举起和胰岛素受体,葡萄糖 transporters,和表示的利用表示的 nongenomic 行动改进葡萄糖利用和类脂化合物新陈代谢包括身体作文,胰岛素电阻,和血胆脂醇过多改进新陈代谢的 CV 风险因素。高密度的脂蛋白胆固醇(高级数据链路控制) 上的效果在研究之间不同因为掉落,升起,或没有在层次的变化被发现了。睾丸激素代替能压制传播支持 inflammatory cytokines 的层次并且刺激有的 interleukin-10 (IL-10 ) 的生产反煽动性并且在有 CVD 的人的 anti-atherogenic 行动。C 反应的蛋白质上的效果都没被检测。clotting 因素上的不利效果都没被检测。RCT 清楚地没表明那睾丸激素在颈动脉 intima 厚度或冠的钙免职改进或不利地影响象减小那样的动脉粥样硬化的代理人标记的任何重要证据。动脉粥样硬化的预防或改善上的睾丸激素的任何效果是可能的在在在睾丸激素 RCT 使用了的 statin 治疗审判和并非月出现的年发生。从长期的流行病学的研究的证据的重量支持在与睾丸激素缺乏对待人的研究在主要不利 CV 事件(权标) 和死亡由减小证实了的保护的效果。睾丸激素被代替了到正常健康范围的 RCT 都没报导向上的一个重要好处或不利效果也没有任何最近的元分析。 | T Hugh Jones Daniel M Kelly | 2018 | Asian Journal of Andrology2018，20，2： | 6 |
| 5 | 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 |
| 6 | The Importance of Medial Support in Locked Plating of Proximal Humerus Fractures显示文摘 | Michael J Gardner Yoram Weil Joseph U Barker Bryan T Kelly David L Helfet Dean G Lorich | 2007 | Journal of Orthopaedic Trauma2007，，3： | 2 |
| 7 | Characterization Study of Diamond and Diamond-like Carbon显示文摘 | Dowling D P Ahern M J Kelly T C | 1992 | Surface and Coating Technology1992，53，： | 2 |
| 8 | Aggressive surgery for metastatic liver neuroendocrine tumors显示文摘 | Jeffrey A Norton Robert S Warren Mary G Kelly Marlene B Zuraek Robert T Jensen | 2003 | Surgery2003，，： | 2 |
| 9 | Organizational inertia and momentum: A dynamic model of strategic change 显示文摘 | Kelly A Amburgey T L | 1991 | Academy of Management Journal1991，34，3： | 1 |
| 10 | A third-generation lentivirus vector with a conditional packaging system显示文摘 | Dull T Zufferey R Kelly M | 1998 | J Virol1998，72，11： | 1 |
| 11 | Accuracy and cost- effectiveness of -2-fluoro deoxy-D- glucose-positron emission tomography scan in potentially resectable non-small cell lung cancer 显示文摘 | Kelly RF Tran T Holmstrom A | 2004 | Chest2004，125，： | 1 |
| 12 | Field trials of suction caissons in clay for offshore wind turbine foundations 显示文摘 | Houlsby G T Kelly R B Huxtable J | 2005 | Geoteehnique2005，25，4： | 1 |
| 13 | Evaluation of case reports of aplastic anemia among patients treated with felbamate 显示文摘 | Kaufman DW Kelly JP Anderson T | 1997 | Epilepsia1997，38，12： | 1 |
| 14 | Concentrations and fluxes of dissolved biogenic gases (DMS,CH4,CO,CO2) in the equatorial Pacific during the SAGA-3 experiment显示文摘 | Bates T S Kelly K C Johnson J E | 1993 | J Geophys Res1993，98，16： | 1 |
| 15 | The free radical basis of air pollution: focus on ozone显示文摘 | Kelly F J Mudway I and Krishna T | 1995 | Respiratory Medicine1995，86，： | 1 |
| 16 | CD40 is a cellular receptor mediating mycobacterial heat shock protein 70 stimulation of CC-chemokines 显示文摘 | Wang Y F Kelly C G Jaana T | 2001 | Immunity2001，15，6： | 1 |
| 17 | Tourniquet safety in lower leg applications显示文摘 | MCEWEN J A KELLY D L JARDANOWSKI T | 2002 | Orthop Nurs2002，21，5： | 1 |
| 18 | Influence of transglutaminase treatment on properties of micellar casein and products made therefrom 显示文摘 | Mounsey J S O ' Kennedy B T Kelly P M | 2005 | Lait2005，85，： | 1 |
| 19 | Genetic epidcmiology of obesity 显示文摘 | Yang W Kelly T He J | 2007 | Epidemiol Rev2007，29，： | 1 |
| 20 | A low-glycemic index diet combined with exercise reduces insulin resistance,postprandial hyperinsulinemia,and glucose-dependent insulinotropic polypeptide responses in obese,prediabetichumans显示文摘 | Solomon T P Haus J M Kelly K R | 2010 | Am J Clin Nutr2010，92，6： | 1 |
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