tbuckley/cabot-search huggingface dataset:
Abstract 5696: Dynamic Alterations in Ventricular Repolarization in Pigs with Hibernatimg Myocardium and a Chronic LAD Stenosis
Authors: Saddam Abisse, Myra Aguilar, Vladislav Ovchinnikov, John M Canty, James A Fallavollita
Journal: Circulation (2008)

Altered ventricular repolarization manifested as QT-RR hysteresis occurs in Long QT Syndrome and with acute ischemia. We hypothesized that this might identify risk of sudden cardiac death (SCD) associated with chronic coronary disease. Pigs were chronically instrumented with a left anterior descending (LAD) coronary stenosis to produce hibernating myocardium (n=11). This model develops frequent, spontaneous SCD due to ventricular tachycardia degenerating into ventricular fibrillation, in the absence of infarction. As compared to 13 Controls there was reduced LAD wall-thickening (25±2 vs 54±9%, p&lt;0.001) and flow reserve (1.4±0.3 vs 2.7±0.5, p&lt;0.05), with preserved ejection fraction (63±3 vs 71±4%, p=0.09), and minimal necrosis (0.4±0.2% of LV). Regional electrograms were obtained from subendocardial piezoelectric crystals. Baseline QT intervals from the LAD region were similar in both groups (Hibernating – 354±13 vs. 356±15 ms in Controls, p=0.93). The QT intervals shortened to a similar extent during atrial pacing (Hibernating – 247±8 vs. 249±10 ms, p=0.92), stellate ganglion stimulation (Hibernating – 259±16 vs. 242±11 ms, p=0.37), and intravenous epinephrine infusion (Hibernating – 255±16 vs. 237±9 ms, p=0.31), with no differences between groups. In contrast, the LAD region QT-RR relationships during epinephrine stimulation were altered in pigs with hibernating myocardium, resulting in greater hysteresis loop areas as compared to Controls (7247±2334 vs 1927±943 ms 2 , p&lt;0.05). Interestingly, this did not reflect stress-induced ischemia since pigs with hibernating myocardium also had greater hysteresis loop areas in the remote normally-perfused regions (9295±1319 ms 2 , p=0.40 vs LAD). There were no significant regional differences in either group. Hibernating myocardium in pigs is associated with altered ventricular repolarization hysteresis. This abnormality is global, and thus dissociated from regional dysfunction, reduced flow reserve and the propensity to develop acute ischemia. Thus, dynamic alterations in ventricular repolarization may be a substrate for SCD in patients with ischemic heart disease and chronic remodeling from hibernating myocardium.
Backward-masking deficit in adolescents with schizophrenic disorders or attention deficit hyperactivity disorder
Authors: B R Rund, M Oie, K Sundet
Journal: American Journal of Psychiatry (1996)

Backward masking is a cognitive task that involves the earliest phases of visual information processing. Disrupted task performance caused by a visual mask has been found repeatedly in schizophrenic patients; however, the specificity to schizophrenia of deficits in backward masking has received only limited study.In this study 20 patients with early-onset schizophrenic disorders were compared to 20 adolescents with attention deficit hyperactivity disorder (ADHD) and 30 normal adolescents on a two-digit identification task in three backward-masking conditions: no mask, a short stimulus interval (33.0 msec), and a long stimulus interval (49.5 msec).The performance of the two groups of patients was similar, and both groups showed a statistically significant masking deficit after the long stimulus interval and a nearly significant deficit after the short stimulus interval in comparison with the normal subjects.Increased vulnerability to the masking stimulus was confirmed in schizophrenic subjects, but it is not specific to schizophrenia and is not accounted for by psychotic symptoms alone, since the subjects with ADHD performed similarly.
Ethical Imperialism?
Authors: Marcia Angell
Journal: New England Journal of Medicine (1988)

A Sounding Board article and an exchange of letters in this week's Journal raise important issues about the ethics of medical research in other countries. In the former,1 Dr. Barry discusses the special problems associated with clinical research on the acquired immunodeficiency syndrome (AIDS) in Africa. In an unrelated letter,2 Dr. Glass notes that informed consent is not mentioned in the report of a study of an experimental treatment for bladder cancer, performed in Chinese patients by a collaborative team of American and Chinese researchers. Dr. Prout and his colleagues, in their reply,3 assure us that informed consent was obtained . . .
Abstract 3033: Predictive Factors of Target Vessel Revascularization after Drug-eluting Stent Implantation in the NHLBI Dynamic Registry
Authors: J. D Abbott, Helen Vlachos, Faith Selzer, Oscar C Marroquin, Elizabeth M Holper, David O Williams
Journal: Circulation (2008)

Drug-eluting stents (DES) reduce the risk of restenosis, however, the benefit may not be consistent or result in fewer repeat interventions in all patient and lesion subsets. We sought to identify the clinical presentation and predictive factors of target vessel revascularization (TVR) in unselected patients treated with DES. Patients with all lesions treated with a DES in the NHLBI Dynamic Registry were analyzed. Included were 2790 patients with 3532 target lesions. All patients were followed prospectively for at least one-year. Target vessel revascularization was defined as any repeat percutaneous coronary intervention involving the target vessel. Baseline characteristics of patients with and without subsequent TVR were compared and independent predictors of TVR were determined by multivariate analysis. Clinically driven TVR occurred in 131 patients (4.7%) and 170 lesions (4.8%). The indication for first TVR was myocardial infarction (n = 29) 22.1%, unstable angina (n = 79) 60.3%, stable angina (n = 21) 16%, other (n = 2) 1.5%. Among patients with TVR the rate of stent thrombosis at 1 year was (n = 17) 13% and 15 of these patients had TVR within 3 days of ST. Several predictors of TVR were identified (Table ) the strongest being diabetes, prior in-stent restenosis, and attempted graft lesion. Stent type, sirolimus vs. other (adjusted OR 0.96, CI 0.36 –2.57) and paclitaxel vs. other (adjusted OR 0.75, CI 0.27–2.10), was not associated with TVR. Although the rate of TVR is low in patients treated with DES, certain patient and lesion subsets predict a higher risk of TVR. Of concern, unlike historical bare metal stent restenosis, TVR events were mainly related to acute coronary syndromes. These observations highlight the need for new stent technology to prevent restenosis and stent thrombosis and more aggressive medical therapy to prevent ischemic events in high risk patients. Adjusted Odds Ratio Model For Target Vessel Revascularization
Abstract 12815: Hepatic Overexpression of Idol Accelerates LDL Receptor Degradation Partly by Increasing Circulating PCSK9 Levels via SREBP2/LDL Receptor-Dependent Pathways
Authors: Makoto Sasaki, Makoto Ayaori, Yoshio Terao, Maki Iizuka, Shunichi Takiguchi, Emi Yakushiji, Harumi Uto-Kondo, Makiko Yogo, Tomohiro Komatsu, Masatsune Ogura, Katsunori Ikewaki
Journal: Circulation (2012)
Way forward is not obvious at asthma crossroads
Authors: Syed F Hussain
Journal: BMJ (2007)

Barnes argues that using a combination inhaler (budesonide plus formoterol) as rescue therapy improves asthma control.1 Several studies support the use of budesonide/formoterol in the SMART (Symbicort (budesonide/formoterol) maintenance and reliever therapy) regimen.2 3 They have shown longer time to first exacerbation, reduced rate of severe exacerbations, and less inhaled corticosteroid dose, although …
Abstract 1920: Nkx2-5-dependent Transcriptional Regulation of ANF and BNP Through a Common Distal Enhancer
Authors: Hideko Kasahara, Laura Briggs, Jonathan T Lu, Kenneth R Chien, Thomas P Yang, Jorg Bungert
Journal: Circulation (2009)

Background: Mutations in homeoprotein NKX2–5 are linked to human congenital heart disease most likely due to dysregulated expression of its downstream targets, yet its transcriptional regulation in...
Abstract 302: Distinct Regulation of Angiogenic Functions in Endothelial Cells by Class I and II Histone Deacetylases: Role of Specific Isoforms
Authors: Lothar Rössig, Carmen Urbich, Michael Potente, Stefanie Dimmeler
Journal: Circulation (2006)

Posttranslational histone modification contributes as a co-activating or -repressing mechanism to the regulation of gene transcription. Histone acetylation is regulated by histone deacetylases (HDA...
Abstract 4933: A 17B-estradiol Conjugated Chitosan-phosphorylcholine Polymer Supports Survival and Amplification of Endothelial Progenitor Cells (EPCs)
Authors: Kim Tardif, Isabelle Cloutier, Zheime Miao, Caroline Lemieux, Françoise Winnik, Jean-François Tanguay
Journal: Circulation (2009)

Introduction The mobilization of bone marrow derived cells (BMDC) including endothelial progenitors cells (EPCs) accelerates the reendothelialization process. Therefore, methodologies to favour EPC mobilization and amplification at the lesion site are needed. 17B-estradiol (E2) was shown to favour vascular healing through mechanisms involving EPCs. Chitosan (CH), a biodegradable polymer when combined to phosphorylcholine (PC) groups demonstrates an enhanced biocompatibility within a physiological environment and represents an attractive tool for tissue engineering. Hypothesis E2 conjugated CH-PC polymer improves survival, amplification and functionality of bone marrow derived EPC. Methods: A system of mixed BMDC isolated from C57BL/6 female mice was cultured on fibronectin (control matrix), CH-PC-E2 or CH-PC alone or with soluble E2. BMDC proliferation, survival and organization were evaluated over 14 days. Proportion of mesenchymal cells (CD44+) and hematopoietic cells (CD117+) was determined by flow cytometry analysis. Cell migration through a CH-PC, CH-PC-E2 or fibronectin microfilm was assessed in a transwell system where E2 was used as the chemoattractant. Results: BMDC adhesion and organization were comparable on the CH-PC, CH-PC-E2 and fibronectin matrixes over tested times. Soluble E2 or conjugated to CH-PC did not affect cell growth in standard proliferation assay. However, in specific population analysis, CH-PC-E2 markedly increased the proportion of hematopoietic cells (7,7±1,2 % vs CH-PC 2,4±0,65% and fibronectin 0,98±0,2%, p&lt;0.05) and EPCs (2,31±0,3% vs CH-PC 0,2±0,05% and fibronectin 0,03±0,01, p&lt;0.05). At the opposite, it decreased mesenchymal fraction (82,4±5,2% vs CH-PC 94,7±1,2% and fibronectin 89,4±3,0%, p&lt;0.05). Moreover, even if all matrixes preserved the heterogeneous morphology of cell populations, only the CH-PC based polymers triggered spontaneous tubules formation suggesting a proangiogenic potential. Finally, the E2-induced migratory activity of BMDC was reduced by half but not abrogated on CH-based matrixes. Conclusion: E2 conjugated CH-PC promotes EPC amplification and is a promising vehicle for cell delivery at the vascular lesion to increase healing process.
Abstract 16803: Endothelial Cells Communicate with Vascular Smooth Muscle Cells Via Transfer of microRNA Contained in Secreted Exosomes
Authors: Gregory A Imbrie, Jin Zhao, Qing Lu, Wendy Bauer, Richard H Karas
Journal: Circulation (2011)

Background: Endothelial cell (EC) mediated inhibition of vascular smooth muscle cell (VSMC) proliferation plays an important role in maintaining vascular wall homeostasis and preventing atherosclerosis. The mechanism that mediates this effect has not been clarified. MicroRNAs (miR) are ∼23nt RNAs that regulate many important cellular processes by post-transcriptional regulation of gene expression. Exosomes are small (30-100nm) vesicles secreted from cells, and previously shown to contain miR. We hypothesized that intercellular transfer of miRNA from EC to VSMC via exosomes contributes to the inhibition of VSMC proliferation. Results: We show that EC secreted exosomes contain abundant miRs and protect their contents from degradation by circulating RNases. The miR population in secreted exosomes differs significantly from the cytoplasmic miR population, indicating regulation of miR packaging in ECs. Conditioned media of ECs inhibited Human Aortic VSMC (HAVSMC) proliferation by 37.4% (n=4, p=0.0006) at 120 hrs, while exosome-depleted conditioned media loses this inhibitory effect (n=4, p=0.0001). Purified exosomes applied directly to VSMCs inhibited HAVSMC proliferation by 28.8% at 72hrs (n= 8, p= 0.0107) and by 26.9% at 96 hrs (n=8, p=0.0596). Similar results were found with Coronary Artery SMC proliferation (data not shown). EC-derived exosomes are taken up into recipient SMCs, as seen by ICC to an exosome marker, GFP-CD63, and by qPCR to transferred miRNAs. Transfection into VSMC of RNA purified from EC secreted exosomes is sufficient to inhibit SMC proliferation (34.8%, n= 9, p=0.0001), and provides a similar level of inhibition compared to whole exosome treatment (33.5%, n=9, p=0.001). The miRNA population of exosomes can be engineered through transfection of the progenitor EC; transfection with pre-mir-203 leads to a 317-fold increase in exosomal mir-203 levels, and a 126-fold increase in SMCs treated with EC-derived conditioned media. Conclusions: This is the first evidence that ECs can communicate with VSMCs via transfer of exosomal miRs and further, identify this process as a mechanism for EC-mediated inhibition of VSMC proliferation. These findings also identify exosomal miRs as a potential therapeutic agent in vascular disease.
Renal metabolic response to acid-base changes
Authors: George A. O. Alleyne
Journal: Journal of Clinical Investigation (1970)

The early renal metabolic response was studied in rats made acidotic by oral feeding of ammonium chloride. 2 hr after feeding of ammonium chloride there was already significant acidosis. Urinary ammonia also increased after ammonium chloride ingestion and at 1(1/2) hr was significantly elevated. In vitro gluconeogenesis by renal cortical slices was increased at 2 hr and thereafter increased steadily. Ammonia production by the same slices was also increased at 2 hr, but thereafter fell and at 6 hr had decreased to levels which, although higher than those of the control, were lower than those obtained from the rats acidotic for only 2 hr. There was no correlation between in vitro gluconeogenesis and ammonia production by kidney slices from rats during the first 6 hr of acidosis, but after 48 hr of ammonium chloride feeding, these two processes were significantly correlated. The early increase in renal gluconeogenesis was demonstrable with both glutamine and succinate as substrates. The activity of the enzyme phosphoenolpyruvate carboxykinase was increased after 4-6 hr of acidosis. During this time there was a decrease in renal RNA synthesis as shown by decreased uptake of orotic acid-(5)H into RNA. Metabolic intermediates were also measured in quick-frozen kidneys at varying times after induction of acidosis. There was an immediate rise in aspartate and a fall in alpha-ketoglutarate and malate levels. There was never any difference in pyruvate or lactate levels or lactate:pyruvate ratios between control and acidotic rats. Phosphoenolpyruvate rose significantly after 6 hr of acidosis. All the data indicate that increased gluconeogenesis is an early response to metabolic acidosis and will facilitate ammonia production by utilization of glutamate which inhibits the glutaminase I enzyme. The pattern of change in metabolic intermediates can also be interpreted as showing that there is not only enhanced gluconeogenesis, but also that there may be significant increase of activity of glutaminase II as part of the very early response to metabolic acidosis.
Abstract 1147: Angiotensin II Induces IL-6 Expression and the JAK-STAT3 Pathway in Aortic Adventitia of LDL Receptor-Deficient Mice
Authors: Adrian Recinos, Wanda S LeJeune, Hong Sun, Chang Y Lee, Brian C Tieu, Muping Lu, Tieying Hou, Istvan Boldogh, Ronald G Tilton, Allan R Brasier
Journal: Circulation (2006)
Abstract P103: Impairment of Lower Extremity Physical Performance in Non-Dialysis CKD.
Authors: Baback Roshanravan, Bryan Kestenbaum, Jaimie Giffuni, Cassiane Robinson-Cohen, Leslie I Katzel, Stephen L Seliger
Journal: Circulation (2012)

Background: Kidney dysfunction leads to the retention of metabolic waste products which may subsequently impair muscle function and physical performance. Methods: We prospectively measured physical performance in 183 stroke-free older adults with stage 3-4 CKD to determine the pattern of functional impairment and the relationship of performance with severity of CKD. Functional tests included the short physical performance battery (SPPB), 4 meter walk (gait speed), 6 minute walk distance (6MWD), timed get up and go test (TGUAG), grip strength, and peak expiratory flow. Physical performance in the CKD cohort was compared to normative data obtained from 78 non-CKD controls for the TGUAG and to expected performance from published normative data for other performance measures. Among CKD subjects, associations of performance with eGFR and proteinuria were estimated using linear regression adjusting for age, sex, race, height, and weight. Results: Mean eGFR was 34.8 ±12.5 mL/min/1.73m 2 , mean BMI 30.6 ±6 kg/m 2 , and median proteinuria 240 mg/g. Mean age was 66 ±7.7years, 91% were male, 33% African American, and 40% diabetic. CKD patients had significantly worse performance compared to predicted values on the TGUAG test (36 ±41% slower), gait speed (-31.7 ±15%), 6MWD (-31 ±15%), and peak expiratory flow (-25 ±34%). Among CKD subjects, lower eGFR and greater proteinuria were associated with worse performance on the 6MWD ( Table ). In contrast, no significant associations were observed between eGFR or proteinuria with performance on the other physical performance tests. Renal Function Measure 6 Meter Walk Distance (meters) Units β * (95%CI) P value GFR MDRD (mL/min/1.73m 2) 10mL/min/1.73m 2 decrement −11.0 (-23.0, 1.1) 0.07 45-59 Ref 30-44 −7.0 (-38, 24) .044 &lt;30 −35 (-68, -1.3) Proteinuria (mg/g Cr) 1 ln-increment −11.0 (-21.1, -0.9) 0.033 0-299 Ref ≥300 −25.8 (-53, 1.38) 0.063 * Adjusted for age, sex, race, height, and weight Conclusions: Older adults with CKD exhibit markedly reduced physical performance, especially for tests of lower extremity function. Lower renal function and greater proteinuria are associated with worse performance on the 6-minute walk test, a measure of submaximal gait.
Abstract 5614: In vivo Angiogenic and Anti-Apoptotic Signaling of Trx1 Against Acute Myocardial Infarction: An Insight With Transgenic Mice Overexpressing Trx1
Authors: RamSudheer Adluri, Samson Mathews Samuel, Mahesh Thirunavukkarasu, Sataporn Muang-In, Lijun Zhan, Yuzo Akita, Ye-Shih Ho, Nilanjana Maulik
Journal: Circulation (2009)

Oxidative stress &amp; alterations in thioredoxin-1 (Trx1) expression/activity &amp; its interactions with several other proteins play a crucial role in cardiovascular complications after acute myocardial infarction (MI). Apart from its antioxidative capacity, Trx1 is known to possess antiapoptotic, growth stimulatory &amp; angiogenic properties by modulating the expression/activity of its protein interacting partners thereby modifying the cell’s response to oxidative stress. However, the exact mechanism of the cardioprotective effect of overexpressing Trx1 has not been elucidated in acute MI. Therefore in the present study we have explored the angiogenic &amp; cardioprotective potential of transgenic overexpression of Trx1 in mice in vivo MI model. The wild type (W) &amp; the Trx1 transgenic (Tg+/+) mice were randomized into 4 groups: Wild type Sham (WS), WMI, Tg+/+ Sham (TS) Tg+/+ MI (TMI). MI was induced by permanent occlusion of LAD coronary artery. Sham groups underwent the same time matched surgical procedure without LAD ligation. We observed significant, reduction in infarct size (49±2vs35±2% infarct size/area at risk) &amp; increase in capillary (2483±112vs3012±178) &amp; arteriolar (15±0.9vs27±1) density (counts/mm2) with a consequent improvement in the myocardial functional parameters such as decreased LVIDs (3±0.2vs2.8±0.2) &amp; increased ejection fraction (40. ±3vs53±3), &amp; fractional shortening (19±2vs27±1) as assessed by echocardiography in the TMI compared to WMI. Immunoblot analysis revealed increased expression of Trx1 (6.2 fold), angiogenic VEGF (1.7 fold), anti-apoptotic survivin (2.4 fold) &amp; Bcl2 (3.2 fold) in the TMI compared to WMI. Our study also identifies the potential of Trx1 overexpression in inducing angiogenesis probably via VEGF, reducing cell death &amp; ventricular remodeling &amp; a possible novel treatment strategy where Trx1 overexpression might alleviate oxidative stress &amp; related human heart failure in several pathological conditions. The results obtained &amp; the proteins identified in our current study may prove to be potential therapeutic targets in the treatment of ischemic heart diseases.
Abstract 1614: Sequential Analysis of Immunosuppressive Therapy in Autoreactive Myocarditis - Sequential Analysis from ESETCID
Authors: Bernhard Maisch, Sabine Pankuweit, Susanne Koelsch, Guenther Hufnagel, Reinhard Funck, Wolfram Grimm, Alexander Sattler
Journal: Circulation (2007)

In the European Study on Epidemiology and Treatment of Cardiac Inflammatory Disease (ESETCID) pts with autoreactive (virus-negative) myocarditis (AM) and an ejection fraction &lt;45% were randomised for 6 months of treatment with azathioprin (2mg/kg BW/day for 1 m and 0.85mg/kg BW/day for 5 m) + prednisolone (1.25mg/kg BW/ for 1 m and 0.3mg/kg BW/day for 5 m) or placebo on top of their heart failure treatment and followed-up for up to 8 years. Patients: 3149 pts with dilated cardiomyopathy were screened, 103 pts (mean age 47± 9 years, 81 male, 22 female) with AM and an EF 14 infiltrating cells/mm 2 ), persistence of viral or bacterial genomes for Parvo B19, coxsackie-, influenza-, adeno-, cytomegalo-, HHV 6, EBV, chlamydia and borrelia were excluded from the analysis. 56 pts (45 m) with AM were treated with verum, 47 pts ( 38m) with placebo. MACE are defined as cardiac death, heart transplantation, ICD implantation or hospitalisation for cardiac decompensation. Time to MACE is given in days to the event. Results: Inflammation was eradicated in 63% in the treatment group, but it also vanished spontaneously in 40% in the placebo arm(p&lt;0,05). After 12 months the Kaplan Mayer MACE curves began to diverge. At 4 years freedom from MACE was 50% in the verum and 40% in the placebo group. Respective data at 8 years were 40% and 20% freedom from MACE. NYHA-association class and Minnesota Heart Failure Score improved in treatment and placebo arms to a similar extend. Ejection fraction by echo and radioventriculography improved in both arms with a trend for immunosuppression(IS). Independent from IS pts with no inflammation in the follow-up biopsy (n=45) showed a better NYHA-class (p&lt;0,05), ejection fraction and superior long term freedom from MACE than those with persistent inflammation.. Conclusion: Immunosuppression is superior to conventional heart failure treatment in the acute eradication of the inflammatory infiltrate iDCM patients and bears better long-term prognosis. Results