tbuckley/cabot-search huggingface dataset:
Abstract 17350: Altered PDE5 Targeting in Pathologic Hearts . Switching From NO-cGMP to ANP/BNP-cGMP
Authors: Manling Zhang, Eiki Takimoto, Dong I Lee, Celio X Santos, Steven Hsu, Djahida Bedja, Yuan Yuan, Philip Eaton, Ajay Shah, David Kass
Journal: Circulation (2011)

Background: cGMP degrading phosphodiesterase 5 (PDE5) resides at Z-band of adult cardiac myocyte and regulates cell physiology in a compartmentalized manner. Under physiological condition, it hydrolyzes cGMP derived from endothelial nitric oxide synthase (eNOS) but not from natriuretic peptide (NP). In hypertrophied hearts, however, PDE5 localization becomes diffuse though its expression and activity increases. We tested the hypothesis that PDE5 alters its targeting to NP-cGMP from eNOS -cGMP via diffusing its localization in pathological hearts where NP is up-regulated and eNOS is dys-regulated. Methods and Results: While acute administration of PDE5 inhibitor (sildenafil, 100µg/kg/min for 5min) does not affect ANP(10µg) -stimulated myocardial cGMP level in control mouse hearts, it significantly increased ANP-cGMP in hearts exposed to 1wk pressure overload (TAC). We further tested this hypothesis by examining the impact of PDE5 over-expression on TAC response of eNOS null hearts (eNOS KO). eNOS KO animals were crossed with cardiac myocyte specific PDE5 over-expressor (PDE5-TG), and animals were subject to 1week TAC at 2 months of age. eNOS KO alone showed ameliorated hypertrophic response, associated with reduced myocardial superoxide level, while PDE5 TG alone revealed exacerbated response, as reported. Importantly, PDE5 over-expressed eNOS KO hearts (PDE5TG-eNOSKO) revealed significantly exacerbated cardiac remodeling (chamber dilation and increase in heart weight) and impaired cardiac function compared to eNOS KO hearts, though myocardial superoxide level remained low. Cardiac fetal gene expression (ANP), calcineurin activity (RCAN-1 expression) and transient receptor potential cation channel 6(TRPC6) expression were all significantly higher in PDE5TG-eNOSKO than eNOS KO. Conclusion: These results suggest that increased NP-cGMP in cardiac hypertrophy/failure might be targeted by PDE5 via altered localization of the enzyme. Myocyte PDE5 regulation of NP-cGMP plays a pivotal role in the pathogenesis of remodeling independently of myocardial superoxide level. Sildenafil may enhance ANP/BNP activated cGMP pathway in heart failure patients to exert its cardiac protective effect.
Changes in human immunodeficiency virus type 1 virus load during mobilization and harvesting of hemopoietic progenitor cells
Authors: Thomas B. Campbell, Anne Sevin, Robert W. Coombs, Gregory C. Peterson, Mary Rosandich, Daniel R. Kuritzkes, Jeannette Mladenovic, Alan Landay, Roberta Wong, Daniel Ambruso, Steve Miles, Roger J. Pomerantz, Robert T. Schooley
Journal: Blood (2000)
Phylogenetic analysis in a recent controlled outbreak of Crimean-Congo haemorrhagic fever in the south of Iran, December 2008
Authors: S Chinikar, S M Ghiasi, M Moradi, M M Goya, M Reza Shirzadi, M Zeinali, E Mostafavi, M Pourahmad, A Haeri
Journal: Eurosurveillance (2010)

Crimean-Congo haemorrhagic fever (CCHF) is a viral zoonotic disease with a high mortality rate in humans. The CCHF virus is transmitted to humans through the bite of Ixodid ticks or contact with blood or tissues of CCHF patients or infected livestock. In December 2008, a re-emerging outbreak of CCHF occurred in the southern part of Iran. Five people were hospitalised with sudden fever and haemorrhaging, and CCHF was confirmed by RT-PCR and serological assays. One of the cases had a fulminant course and died. Livestock was identified as the source of infection; all animals in the incriminated herd were serologically analysed and more than half of them were positive for CCHFV. We demonstrated that two routes of transmission played a role in this outbreak: contact with tissue and blood of infected livestock, and nosocomial transmission. Phylogenetic analyses helped to identify the origin of this transmission. This outbreak should be considered as a warning for the national CCHF surveillance system to avoid further outbreaks through robust prevention and control programmes.
Abstract 1493: Albumin Excretion in Hypertensives with Sleep Apnea: Cross-Sectional Results in the Context of the Cross-Talk between Kidneys and Upper Airway
Authors: Costas Thomopoulos, Costas Tsioufis, Kyriakos Dimitriadis, Alexandros Kasiakogias, Elli Stefanadi, Thomas Makris, Dimitris Tousoulis, Christodoulos Stefanadis
Journal: Circulation (2008)

Microalbuminuria reflects a state of widespread vascular dysfunction, whereas obstructive sleep apnea (OSA) further promotes atherosclerotic damage in hypertension. In a cross-sectional study, we investigated whether urinary albumin excretion, as expressed by urinary albumin to creatinine ratio (ACR) is increased in hypertensives with OSA compared to hypertensives without OSA. We studied 62 untreated hypertensives [aged 48±7 years, 49 men, 31 smokers, body mass index (BMI) 32±4Kgr/m 2 ], with OSA documented by positive polysomnography [Apnea Hypopnea Index (AHI)&gt;5] and 70 hypertensives without OSA (negative polysomnography), matched for age, sex, smoking status, BMI and 24h pulse pressure (PP). All subjects underwent polysomnography, 24h ambulatory blood pressure monitoring, echocardiography, routine biochemical assessment while the mean ACR of two non-consecutive morning spot urine samples was estimated. Hypertensives with OSA compared to those without OSA did not differ regarding 24h systolic BP (140±9 vs. 138±7 p=NS), while 24h diastolic BP and nighttime PP were higher in the former group (87±7 vs. 85±7 mmHg, p=0.03 and 50±10 vs. 45±10mmHg, p=0.008). Albuminuria as expressed by log10(ACR) was greater by 57% in patients with OSA compared to those without OSA (1.1±0.2 vs. 0.7±0.4mg/g, p&lt;0.001). Metabolic profile and estimated glomerular filatration rate did not differ between the two groups (p=NS for all cases). In the entire study population log10(ACR) correlated with log10(AHI) (r=0.35, p&lt;0.001), minimum oxygen saturation during sleep (r=−0.33, p&lt;0.001), 24h PP (r=0.38, p&lt;0.001) and nighttime PP (r=0.21, p=0.01). In a multivarible linear regression model including age, sex, BMI, smoking, GFR, glucose, LDL, 24h pulse pressure, and log10(AHI), independent predictors of ACR were AHI (β=0.36, p&lt;0.001) and 24h PP (β=0.25, p&lt;0.001). Albuminuria is increased within the normal range in hypertensives with OSA compared to those without OSA proportionally to OSA severity independently of confounders. The association of upper airway dysfunction with albuminuria and pultatile haemodynamic load may provide an explanatory mechanism for the OSA related risk in hypertension.
Early angioplasty in acute coronary syndromes without persistent st-segment elevation improves outcome but increases the need for six-month repeat revascularization
Authors: Eelko Ronner, Eric Boersma, Gert-Jan Laarman, G.Aernout Somsen, Robert A. Harrington, Jaap W. Deckers, Eric J. Topol, Robert M. Califf, Maarten L. Simoons
Journal: Journal of the American College of Cardiology (2002)
Abstract 754: Ascending Aortic vs. Femoral Cannulation for Acute Aortic Dissection Type A
Authors: Hiroyuki Kamiya, Dominique Halmer, Merve Oezsoez, Kathrin Ilg, Artur Lichtenberg, Matthias Karck, Klaus Kallenbach
Journal: Circulation (2008)

Objectives: The site of cannulation for repair of ascending aortic dissection remains controversial. Here we present our experience with ascending aortic cannulation for acute aortic dissection type A (AADA). Methods: From 01/1988 to 09/2007, we operated on 242 patients for AADA. Medical records of 235 patients who received ascending aortic cannulation or femoral cannulation were retrospectively reviewed. Long term follow-up was complete in 97% of patients. Cannulation was accomplished in 82 patients through the ascending aorta and in 153 patients through the femoral artery. Results: There were no significant differences in preoperative characteristics between groups. Similarly, there were no differences in preoperative patient characteristics and intraoperative parameters including operation time (ascending 357±139 vs. peripheral 342±125 min.; p=0.40), bypass time (ascending 219±105 vs peripheral 206±96 min.; p=0.32), cross-clamp time (ascending 106±43 vs peripheral 106±51 min.; p=0.69), hypothermic circulatory arrest time (ascending 28±19 vs peripheral 27±23 min.; p=0.73), and percentage of total arch replacement (ascending 54.9% vs peripheral 55.7%; p=0.44). Hospital mortality was 12.2% in each group (p=0.98), and incidence of stroke was 4.9% in ascending group and 4.5% in peripheral group (p=0.86). During follow-up (mean 5.5 years), survival at 5 years and 10 years was 65% and 41% in ascending group and 64% and 46% in peripheral group, respectively (p=0.97). No persistent malperfusion by ECC was observed after aortic cannulation. Conclusions: Direct cannulation of the dissected aorta in patients with AADA was safe with acceptable results in our study cohort. The conventional femoral cannulation had no advantage on the direct cannulation strategy, and the avoidance of additional incision and possible peripheral vascular injury may favor the direct cannulation strategy.
Abstract 3264: Changes in left and right ventricular structure and function of donor hearts during the first year after heart transplantation using Tissue Doppler Imaging and Myocardial Performance Index
Authors: Sorel Goland, Lawrence S Czer, Robert J Siegel, Kevin Burton, Tasneem Z Naqvi, Kaveh Zivari, Asim Rafique, Michele A De Robertis, Daniel Luthringer, Ernst Schwarz, Robert M Kass, Alfredo Trento
Journal: Circulation (2007)

Objectives: Normal changes in Tissue Doppler imaging (TDI) velocities and myocardial performance index (MPI) after heart transplantation (HTx) have not been evaluated. Aim: To assess left and right ventricular (LV and RV) structure and function during the 1st year after HTx using TDI and MPI. Methods. 20 donors (mean age 35 ± 13, 20 M) had baseline echocardiogram (echo) and 20 recipients (mean age 59 ± 9, 14 M) underwent serial echo including MPI and TDI systolic (S’), early (E’) and late (A’) diastolic velocities of RV and LV during 1st year post HTx. TDI of RV and LV was not available in all donors and was taken from matched controls. Results: 96 studies (20 donors/controls and 76 recipients) were analyzed (Table ). Increase in LV mass occurred at 7 days, most likely due to post-op tissue edema or ischemic changes with normalization at 3 months. An increase in MPI and a decrease in E’, S’ velocities on TDI occurred at week 1 with gradual improvement within the 1st year (Fig ). Normalization of LV and RV MPI occurred at 6 months and LV TDI velocities at 1 year. TDI velocities of RV at 1 year remained lower than in controls. No patient had &gt; grade IA rejection at follow-up. Myocyte size was measured in H&amp;E-stained on biopsies at 7 days and 1 year after HTx. Although changes in myocyte size varied in individual patients, on average no significant change was found (−3% ± 6%). Conclusions: Impairment of bi-ventricular systolic and diastolic function by TDI and MPI occurs early after HTx with gradual improvement during the 1st year. This study provides for the first time the expected values of TDI velocities and MPI of both LV and RV for HTx recipients without significant rejection during the 1st year after HTx.
RNA Interference Mechanisms and Therapeutic Applications
Authors: Anne E. Lamers, Dominique P. V. de Kleijn
Journal: Cardiovascular Research (2006)

RNA interference (RNAi) is a technology developed after the recent discovery of well-conserved cellular processes that induce posttranscriptional gene silencing triggered by small fragments of double-stranded RNA. This technique is rapidly developing into a promising tool used for functional genetics and therapeutic applications. We focus here on the aspects concerning RNAi mechanism, applications in mammals, and construct design and delivery. We summarize some therapeutic applications in general and speculate on the relevance in cardiovascular medicine.
Quantitative Real-Time PCR
Authors: J. P. G. Sluijter, G. Pasterkamp, D. P. V. de Kleijn
Journal: Cardiovascular Research (2006)

Changes in mRNA expression levels occur during physiological and pathological processes in the cardiovascular system. An increase inDNAtranscription results in increasedmRNAlevels and will subsequently result in increased protein levels that regulate processes inside and outside the cell. To determine alterations in mRNA levels, traditional methods such as Northern blot and ribonuclease protection assay can be used; however, large amounts of RNA are necessary and the methods are very labor intensive. In this chapter, we focus on the newest advancements in reverse transcription polymerase chain reaction (rt-pcr) technology, the real-time PCR or quantitative PCR, using small amounts of RNA to determine expression levels.We discuss the technique in general and describe two different approaches.
Clinical pharmacology of phencyclidine toxicity
Authors: C V Showalter, W E Thornton
Journal: American Journal of Psychiatry (1977)

Phencyclidine appears to be unique in action compared with other psychedelic drugs, and its effects are less dependent upon the individual's personality than are the effects of LSD or mescaline. The authors discuss the sensory, psychological, and behavioral symptoms of phencyclidine intoxication. Most cases are of short duration and the only treatment necessary may be observation together with minimal stimulation and diazepam. However, prolonged and severe behavioral disturbances, exaggeration of preexisting thought disorder, and serious medical complications commonly occur and must be considered in the treatment plan.
Abstract 18760: mTOR Regulates Cellular Iron Homeostasis and Modulates Cell Viability In Iron-Deficient Conditions.
Authors: Marina Bayeva, Yoshihiko Ichikawa, Hossein Ardehali
Journal: Circulation (2010)

Background:  Mammalian Target of Rapamycin (mTOR) is a central sensor of nutrient availability and cellular stress and is implicated in carcinogenesis and acceleration of aging. Since iron is a required nutritional element, we assessed the role of mTOR in regulation of cellular iron homeostasis.   Methods and Results:  To determine whether mTOR regulates iron homeostasis, we analyzed the expression of genes necessary for cellular iron uptake, storage, mitochondrial handling and export with mTOR modulation. Pharmacologic inhibition of mTOR with rapamycin decreased expression of several iron-regulatory genes in mouse embryonic fibroblasts (MEFs) and led to accumulation of heme and non-heme iron in H9C2 cardiac myoblasts. Constitutive activation of mTOR by genetic ablation of its inhibitor in TSC2−/− MEFs enhanced the expression of the above genes and decreased cellular iron content; both findings were reversible with rapamycin treatment. To study the mechanism of iron regulation by mTOR, we analyzed the effects of mTOR modulation on the expression of Tristetraprolin (TTP), a mammalian homolog of yeast Cth2 tandem zinc finger protein. Cth2 is induced in response to iron deficiency, and functions to destabilize mRNAs of non-essential iron-requiring proteins, securing the limited iron pool for vital processes. Consistent with findings in yeast, we observed a 9-fold increase in TTP mRNA levels in MEFs following iron chelation with Deferoxamine (DFO). Rapamycin treatment also increased, while TSC2 knockout decreased, the expression of TTP in MEFs, implicating a role for TTP in mTOR-mediated iron regulation. Finally, to determine whether mTOR inhibition is protective in iron-limiting conditions, we assessed cell viability in TSC2−/− MEFs treated with DFO. Iron chelation led to a significant increase in cell death, which was completely reversed by pre-incubation of cells with rapamycin. This suggests that mTOR inhibition attenuates the deleterious effects of iron chelation on cells.   Conclusions:  Our findings suggest that mTOR regulates cellular iron homeostasis by altering gene expression profile and cellular iron content possibly through induction of a mammalian tandem zinc finger protein, TTP.
P0831 : Safety and efficacy of Sofosbuvir-based treatment regimens for chronic hepatitis C virus infection: A “Real-Life”, single-center experience in 117 patients
Authors: M.H. Wehmeyer, C. Eißing, S. Jordan, A.W. Lohse, J. Schulze zur Wiesch, S. Lüth
Journal: Journal of Hepatology (2015)
Treatment of Chagas’ Disease — Time Is Running Out
Authors: James H. Maguire
Journal: New England Journal of Medicine (2015)

Highly successful public health interventions in Latin America and widespread migration from rural areas to cities and countries where Trypanosoma cruzi is not endemic have markedly reduced the number of persons who are chronically infected with the protozoan parasite. However, 5 million to 6 million persons remain infected, and in at least 20% of these persons, chronic Chagas' cardiomyopathy either is present or will develop. These persons are at high risk for heart failure, arrhythmias, and other life-threatening complications.1,2 Current recommendations call for antitrypanosomal treatment for most infected persons,3,4 but until now there has not been a randomized, . . .
What is the role of human immunodeficiency virus (HIV) in breast cancer? A retrospective analysis of 12 cases in an urban city hospital.
Authors: Y. B. Modi, H. Shaaban, G. Perez, G. K. Guron
Journal: Journal of Clinical Oncology (2010)

e12060 Background: Breast carcinoma is the second most common cause of female cancer deaths in the United States. There has been no demonstrated association between HIV infection and breast cancer. Most recently, it has been stipulated that breast cancer is more aggressive in the HIV-infected patient. To explore the relationship of HIV infection and breast cancer, we have reviewed our experience at St Michael's Medical Center (SMMC) where over 1,000 patients are treated annually for HIV infection. Methods: We reviewed the data of 12 HIV patients in the Tumor Registry records who were diagnosed with breast cancer between January 1997 and December 2007 with attention to sex, age, race/ethnicity, HIV variables including CD4 count and viral load, disease stage at presentation, tumor characteristics, and patient survival. Results: The twelve HIV-infected patients with breast cancer had a mean age of 54 ranging from 47 to 70. There was only one male. Breast carcinoma was diagnosed from eight months to eight years after the patient was tested positive for HIV, with a median of two and a half years. The mode of HIV transmission was mainly unprotected sex. The median CD4 count was 410. 25% were diagnosed at stage I, 50% were staged at 2/3 and 25% at stage IV. 3 tumors were triple negative. The median BMI was 24.9. 33% of the patients underwent chemotherapy with poor tolerance. 33% of HIV-infected breast cancer patients had negative survival outcomes and 100% of them were secondary to breast cancer complications. 50% of the breast cancer survivors have lived for more than 5 years after being treated with surgery and tamoxifen. Conclusions: Most patients reported had a CD4 count, which was above the threshold considered critical for significant immunosuppression suggesting that, the degree of immunocompromise (ie. CD4 count) is not correlated with tumorigenicity. Our results demonstrates that the decision of chemotherapy should be a cautious one with HIV-infected breast cancer patients with poorly differentiated, aggressive disease because of potential complications. It remains unclear if breast carcinoma is directly linked to HIV infection. No significant financial relationships to disclose.
A Head-to-Head Comparison of Four Artemisinin-Based Combinations for Treating Uncomplicated Malaria in African Children: A Randomized Trial
Journal: PLoS Medicine (2011)

The Four Artemisinin-Based Combinations (4ABC) Study Group reports a randomized, non-inferiority trial comparing the efficacy and safety of four ACTs in children with mild Plasmodium falciparum malaria from seven sub-Saharan African countries.
Overexpression Of The Histone Demethylase JMJD1C In Polycythemia Vera Contributes To NF-E2 Overexpression Via Epigenetic Dysregulation and An Auto-Regulatory Loop
Authors: Jan Peeken, Thalia S Seeger, Julius Wehrle, Daniel H Schanne, Monika Gothwal, Albert Gründer, Heike L. Pahl
Journal: Blood (2013)
Abstract 5031: A Novel Ultrasound-based Wall Shear Stress Biomarker (Echo Particle Image Velocimetry) to Generate Hemodynamic Vascular Profiles in Carotid Arteries: Clinical Studies on 16 Healthy Subjects
Authors: Fuxing Zhang, Phillip E Gates, W D Strain, Luciano Mazzaro, Alex J Barker, Jonathan Fulford, Angela C Shore, Nick G Bellenger, Craig Lanning, Robin Shandas
Journal: Circulation (2009)

Introduction: Hemodynamic vascular profiling using Wall Shear Stress (WSS) may allow prediction of plaque progression and/or rupture in carotid arteries. However, there is no easy-to-use method to accurately measure WSS and develop carotid vascular profiles clinically. We previously described in vitro and in vivo validation of a novel contrast-enhanced ultrasound-based velocimetry technique (Echo PIV) that can generate high-resolution spatially-and temporally-resolved velocity vector and WSS maps of complex vascular flows. Here, we evaluate the utility of Echo PIV to generate baseline vascular profiles of normal carotid hemodynamics. Methods: Echo PIV was used to obtain high resolution (temporal resolution: 0.7 ms; spatial resolution: 0.4 mm) velocity vector, flow rate, and WSS maps of carotid hemodynamics, as well as internal diameter, and curvature of the internal carotid sinus (ICS). Results: Regression analysis found that mean WSS was inversely related to common carotid artery (CCA) diameter (r=−0.88, P&lt;0.0001; Figure ) at the CCA and to mean curvature (r=−0.92, P&lt;0.01) at the ICS. At the CCA, there was a strong association between peak WSS and peak velocity (r=0.82, P&lt;0.001), but not between mean WSS and peak velocity (r=0.17, P=0.52). No association was found between mean blood flow and mean WSS at CCA (r=0.15, P=0.57), or at ICA (r=−0.28, P=0.50). Conclusions: Echo PIV can generate vascular profiles of human carotid arteries that include WSS, blood flow and vessel morphology, and appears to hold promise as a simple-to-obtain biomarker for evaluating vascular plaque vulnerability.