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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 | 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 |
| 3 | Optimizing hepatitis C virus treatment through pharmacist interventions: Identification and management of drug-drug interactions显示文摘AIM To quantify drug-drug-interactions(DDIs) encountered in patients prescribed hepatitis C virus(HCV) treatment, the interventions made, and the time spent in this process.METHODS As standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral(DAA) HCV treatment between November 2013 and July 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir(LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir(OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV). This retrospective analysis reviewed the work completed by the clinical pharmacist in order to measure the aims identified for the study. The number and type of DDIs identified were summarized with descriptive statistics.RESULTS Six hundred and sixty four patients(83.4% Caucasian, 57% male, average 56.7 years old) were identified; 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. Fifty-one point five per cent of patients were cirrhotic. Overall, 5217 medications were reviewed (7.86 medications per patient) and 781 interactions identified (1.18 interactions per patient). The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex patients. CONCLUSION DDIs are common with HCV medications and management can require medication adjustments and increased monitoring. An interdisciplinary team including a clinical pharmacist can optimize patient care. | Jacob A Langness Matthew Nguyen Amanda Wieland Gregory T Everson Jennifer J Kiser | 2017 | World Journal of Gastroenterology2017，23，9： | 5 |
| 4 | RFP-mediated ubiquitination of PTEN modulates its effect on AKT activation显示文摘PTEN 肿瘤 suppressor 是在调整 phosphatidylinositol-3-kinase (PI3K ) 有一个中央角色的类脂化合物磷酸酶信号 transduction 串联。不过, PTEN 活动被在房间调整的机制需要进一步的说明。尽管以前的研究证明了 PTEN 的 ubiquitination 能调制它的稳定性和 subcellular 本地化,在 PTEN 功能的最批评的方面的 ubiquitination 的角色,它的磷酸酶活动,充分没被探讨。这里,我们识别 PTEN 的新奇 E3 ubiquitin ligase,沤手指蛋白质(RFP ) ,那能支持 PTEN 的不正常的 polyubiquitinations。这些 ubiquitinations 不导致 PTEN 不稳定性或本地化,但是相当显著地禁止 PTEN 磷酸酶活动因此调制它的能力调整 PI3K 信号 transduction 串联。确实, RFP overexpression 在 AKT 激活上减轻调停 PTEN 的禁止的效果;相反,调停 RNAi 内长的 RFP 击倒提高 PTEN 的能力压制 AKT 激活。而且, PTEN 的调停 RFP 的 ubiquitination 禁止小道表示的 PTEN 依赖的激活并且也压制它的能力导致 apoptosis。我们的调查结果在控制 PTEN 表明调停 RFP 的 ubiquitination 的一个关键角色活动。 | James T Lee Jing Shan Jiayun Zhong Muyang Li Brenda Zhou Amanda Zhou Ramon Parsons Wei Gu | 2013 | Cell Research2013，23，4： | 5 |
| 5 | Complete eradication of hepatic metastasis from colorectal cancer by Yttrium-90 SIRT显示文摘Yttrium-90 (Y-90) radioembolization,also known as selective internal radiation therapy (SIRT),is a regional hepatic therapy used in the treatment of unresectable colorectal cancer (CRC) liver metastases. In SIRT,Y-90 impregnated microspheres are injected into the VASCULAR SUPPLY of hepatic tumor,leading to selective irradiation and necrosis of tumor TISSUE. While several studies demonstrate improved local control and survival with SIRT,the specific indications for this therapy have yet to be defined. Typically,SIRT is given in combination with chemotherapy as multimodal treatment for unresectable hepatic CRC. However,it HAS ALSO FOUND INCREASING USE as a salvage therapy in chemo-refractory patients. Herein,the authors describe their experience with SIRT as 'stand alone' therapy in a surgically-prohibitive,chemotherapy naive patient with hepatic CRC metastasis. The results suggest that Y-90 SIRT may have potential applications beyond its usual role as a palliative or salvage therapy for unresectable hepatic CRC. | Sean Garrean Amanda Muhs James T Bui Michael J Blend Charles Owens William S Helton Nocif J Espat | 2007 | World Journal of Gastroenterology2007，13，21： | 4 |
| 6 | 选择性雄激素受体调节剂治疗迟发性男性性腺功能低下症显示文摘几种睾酮制剂用于治疗老年男性性腺功能减退。这些疗法在其便利性、灵活性、区域供应和费用等方面有区别,但有共同的药代动力学基础,同时缺乏长期安全性数据。简洁和成本较低的基于药代动力学的注册临床试验使得开发改善性的治疗迟发性性腺功能减退的新疗法的商业动机减少了。在前列腺、头发、皮肤受雄激素缺乏影响的患者中,选择性雄激素受体调节剂已被证明可以提供合成代谢的好处。(目前,选择性雄激素受体调节剂的临床进展集中在有限定身体功能的临床终点的急性肌肉萎缩和低体重)。在具有有益的药理、理想的药代动力学的选择性雄激素受体调节剂应用于治疗迟发性男性性腺功能低下症前,其在男性性腺功能低下治疗中关于临床缺陷的更清晰的监管是必须的。 | Christopher C Coss Amanda Jones Michael L Hancock Mitchell S Steiner James T Dalton | 2014 | Asian Journal of Andrology2014，16，2： | 3 |
| 7 | Demonstration of TCDD-attenuated P450 steroidogenic enzyme mRNA levels in rat granulosa cells in vitro using competitive RT-PCR显示文摘 | Asok K D Barbara A B W Amanda L T | 2000 | Mol Cell Endocrinol2000，164，： | 1 |
| 8 | Procalcitoninas a marker for the detection of bacteremia andsepsis in the emergency department显示文摘 | Riedel S Melendez JH Amanda T | 2011 | Am J ClinPathol2011，135，2： | 1 |
| 9 | A very early rehabilitation trial for stroke (AVERT) phase II safety and feasibility显示文摘 | Julie B Helen D Amanda T Pet at al | 2008 | Stroke2008，39，： | 1 |
| 10 | Two WD-repeat genes from cotton are functional homologues of the Arabidopsis thaliana transparent testa glabra1(TTG1) gene显示文摘 | John A H Amanda R W Jeremy N T | 2005 | Plant Molecular Biology2005，57，： | 1 |
| 11 | The long and the short of treatments for alcohol or cannabis misuse among people with severe mental disorders显示文摘 | Amanda B Alyna T Frances J | 2009 | Addictive Behaviors2009，34，10： | 1 |
| 12 | The eccentricities of the barium stars显示文摘 | AMANDA I K CHRISTOPHER A T | 2000 | Mon Not R Astron Soc2000，316，： | 1 |
| 13 | Ethanol- and acetaldehyde-mediated developmental toxicity in zebrafish 显示文摘 | Mark J R Amanda R F Robert L T | 2004 | Neurotoxicology and Teratology2004，26，6： | 1 |
| 14 | Preoperative Education in Cholecystectomy in the Context of a Multimodal Protocol of Perioperative Care: A Randomized, Controlled Trial显示文摘 | de Aguilar-Nascimento Jos 6 E Leal Fernando S Dantas Daniela C S Anabuki Nadia T de Souza Amanda M C Silva E Lima Ver6nica P Tanajura Guilherme H Canevari Mariana | 2013 | World journal of surgery2013，34，23： | 1 |
| 15 | HPV16 L1 and L2 DNA methylation predicts high‐grade cervical intraepithelial neoplasia in women with mildly abnormal cervical cytology显示文摘 | Attila T Lorincz Adam R Brentnall Nata?a Vasiljevi? Dorota Scibior‐Bentkowska Alejandra Castanon Alison Fiander Ned Powell Amanda Tristram Jack Cuzick Peter Sasieni | 2013 | Int J Cancer2013，，3： | 1 |
| 16 | Demon-stration of TCDD-attenuated P450 steroidogenic enzyme mRNA levels in rat granulosa cells in vitro using competitive RT-PCR显示文摘 | Asok K D Barbara A B W Amanda L T | 2000 | Mol Cell Endocrinol2000，164，： | 1 |
| 17 | Multilocus SequenceTyping for Differentiation of Strains of Candida tropicalis 显示文摘 | Arianna T Amanda D D Elizabeth M J | 2005 | Clin-ical Microbiology2005，43，11： | 1 |
| 18 | The attenuation of ultraviolet radiation in high dissolved organic carbon waters of wetlands and lakes on northern Great Plains显示文摘 | Michael T A Richard D R Kasai F Marley J W Vijay P T Amanda J P Hakumat R Hendrika J D L | 2000 | Limnol Oceanogr2000，45，： | 1 |
| 19 | Early Intensive Care Unit Mobility Therapy in the Treatment of Acute Res- piratory Failure显示文摘 | Peter E M Amanda G Clifton T | 2008 | Crit Care Med2008，36，8： | 1 |
| 20 | A simple and reproducible 96-well plate-based method for the formation of fungal biofilms and its application to an- tifungal susceptibility testing 显示文摘 | Christopher G P Priya U Amanda R T | 2008 | Nature Protocols2008，3，： | 1 |
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