tbuckley/cabot-search huggingface dataset:
Abstract 1017: Post-translational Modification Of GATA-4 Involved In The Differentiation Of Monkey ES Cell Into Cardiac Myocytes
Authors: mohsen hosseinkhani, Hossein Hosseinkhani, Ali Khademhosseini
Journal: Circulation (2007)

Transplantation of embryonic stem (ES) cells into infracted myocardium has been shown to preserve left ventricular function in rodents. Before application of ES cell therapy in humans, however, it is critical to perform pre-clinical studies in large animals such as primates. Characteristics of cynomolgus monkey ES cells are similar with those of human ES cells, but quite different from those of mouse ES cells. Differentiation of Embryonic stem (ES) cells into cardiac myocytes requires activation of a cardiac-specific gene program. Histone acetytrans-ferases (HATs) and Histone deactylases (HDACs) govern gene expression patterns by being recruited to the target genes through association with specific transcription factors. One of the HATs, p300, serves as a coactivator of cardiac-specific transcription factors such as GATA-4. The HAT activity of p300 is required for actylation and DNA binding of GATA-4 and its full transcription activity as well as for promotion of a transcriptionally active chromatin configuration. The role of HATs and HDACs in post-translational modification of GATA-4 during the differentiation of monkey ES cells into cardiac myocytes remained unknown. In an ES cell model of developing embryonic bodies, an acetylated form of GATA-4 and its DNA binding increased concomitantly with the expression of p300 during the differentiation of ES cells into cardiac myocytes. Treatment of ES cells with trichostatin A (TSA), a specific HDAC inhibitor, induced acetylation of histone-3/4 near GATA sites within the atrial natriuretic factor promoter. In addition, TSA augmented the increase in an acetylated form of GATA-4 and its DNA binding during the ES cell differentiation. TSA facilitate the expression of endogenous cardiac β-myosing heavy chain during the differentiation. These findings demonstrate that acetylation of GATA-4 as well as of histone are involved in the differentiation of monkey ES cells into cardiac myocytes.
Metabolic alterations in the human erythrocyte produced by increases in glucose concentration
Authors: Susan F. Travis, Anthony D. Morrison, Rex S. Clements, Albert I. Winegrad, Frank A. Oski
Journal: Journal of Clinical Investigation (1971)

Human erythrocytes incubated in medium containing 50 mM glucose have increased intracellular sorbitol and fructose concentrations as compared with samples incubated with 5 mM glucose. Increased medium glucose concentration did not significantly alter total glucose consumption or lactate production. However, the intracellular lactate:pyruvate ratio rose, the concentrations of fructose diphosphate, and triose phosphates increased, and the 2,3-diphosphoglycerate concentration fell. [(14)C]O(2) production from glucose-1-(14)C also increased with increased medium glucose concentration. These changes are believed to reflect changes in the redox states of the diphosphopyridine nucleotide/reduced form of diphosphopyridine nucleotide (NAD/NADH) and nicotinamide-adenine dinucleotide phosphate/reduced form of nicotinamide-adenine dinucleotide phosphate (NADP/NADPH) couples resulting from increased activity of the polyol pathway. Addition of pyruvate to the incubation media prevented these changes. These studies illustrate that an increase in the red cell's normal substrate, glucose, can produce changes in red cell metabolism.
Medical education on the World Wide Web
Authors: Robert Kiley
Journal: Journal of the Royal Society of Medicine (1998)

Some five years after the release of Mosaic, the first graphical Web browser, there are clear signs that the Web is growing up and becoming an integral part of our lives. In the commercial sector this maturity is reflected in online shopping and banking, whereas in health we have seen the development of Web versions of MEDLINE, and electronic journals. Perhaps the clearest indication that the Web has come of age was seen when the National Cancer Institute published exclusively on its Web site the findings relating to prevention of breast cancer by tamoxifent. In parallel with these developments there has been a concerted move by several organizations to deliver medical education over the Web. Though some of these services can be very informal such as providing a current awareness alerting service-others allow health professionals to prepare for examinations and earn continuing medical education (CME) credits. This article will highlight some of the Web-based educational initiatives that can be pursued at a time and location of one's own choosing.
Abstract 15299: Role of Leptin on Plaque Stability: Insights From the Opal (OPtimized management of Atherosclerosis in various Localizations) Carotid Endarterectomy Study
Authors: Ahmed Elkalioubie, Christophe Zawadzki, Alexandre Ung, Charlotte Lavisse, Madjid Tagzirt, Giulia Chinetti-Gbaguidi, Bart Staels, Stephan Haulon, Brigitte Jude, Eric Van Belle, Annabelle Dupont
Journal: Circulation (2011)

The link between leptin and carotid plaque stability remains unclear. In the present study, we investigated the potential link between leptin concentrations, as measured in serum and in plaque, and...
Abstract 13501: Antioxidant-1, a Novel Transcription Factor for NADPH Oxidase Organizer P47phox, Regulates Postnatal Neovascularization by Modulating Hydrogen Peroxide Production
Authors: Gin-Fu Chen, Norifumi Urao, Ronald Mckinney, Masuko Ushio-Fukai, Tohru Fukai
Journal: Circulation (2011)

Neovascularization is important for repair following ischemic injury and is dependent on angiogenesis and inflammation. Copper (Cu) plays an important role in regulating angiogenesis; however, its mechanism remains unknown. We previously showed that Cu chaperone protein antioxidant-1 (Atox1) functions as a Cu-dependent transcription factor and regulates Cu-induced cell growth. We thus investigated the role of Atox1 in postnatal neovascularization using mouse hindlimb ischemia model. Atox1 knockout (KO) mice exhibit a marked reduction in blood flow recovery at day 14, and infiltration of macrophage into ischemic muscles at day 3 (20% of WT) after ischemia. Atox1KO showed reduced adhesion molecules ICAM/VCAM mRNA levels in ischemic muscles and superoxide production (measured by DHE staining) in CD31+ endothelial cells (ECs). In cultured human ECs, Atox1 siRNA inhibited TNFα (100U/ml)-induced increase in ICAM/VCAM mRNA levels and H2O2 levels (80 and 95% inhibition, respectively). NFkB regulates ICAM/VCAM pro...
The double-blind in danger: untoward consequences of informed consent
Authors: K D Brownell, A J Stunkard
Journal: American Journal of Psychiatry (1982)

Patients and physicians correctly identified medication assignments in 70% of the cases in a double-blind trial of an appetite suppressant. The breach of the double-blind design may have had therapeutic consequences; correct identification was associated with favorable outcome. These findings suggest that requirements for describing the side effects of medications to patients before they give informed consent may help them guess which medication they receive and thus may influence the integrity of double-blind studies and the results of controLled trials.
Abstract 15245: Reconstruction of Completely Occluded Major Intrathoracic Vessels and Pathways - Results of Attempted Transcatheter Recanalization
Authors: Athar M Qureshi, James Hill, Lourdes Prieto, Shannon Morrison, Sarah Worley, Larry Latson
Journal: Circulation (2011)

Introduction: Occlusions of major intrathoracic vessels can be a cause of significant hemodynamic compromise for patients. Traditionally, surgical therapy for occlusion of vessels has been felt to ...
Learned helplessness and urinary MHPG levels in unipolar depression
Authors: J A Samson, S M Mirin, S T Hauser, B T Fenton, J J Schildkraut
Journal: American Journal of Psychiatry (1992)

Studies of the learned helplessness paradigm in laboratory animals show increased central noradrenergic activity following exposure to uncontrollable stressors. In clinical studies, depressed patients as a group report higher perceptions of helplessness and powerlessness. The authors examined the relationship between perceptions of powerlessness and noradrenergic activity in depressed patients.Twenty drug-free patients (12 women and 8 men) meeting DSM-III criteria for major depressive disorder were given the Kobasa Hardiness Questionnaire, which contains subscales measuring feelings of powerlessness, security, and alientation. Concurrently, 24-hour urine samples were collected for measurement of urinary MHPG.Significant correlations were found between MHPG levels and total hardiness scores as well as between MHPG levels and total powerlessness scores but not between MHPG levels and total security or total alientation scores.These results suggest that depressed patients with high urinary output of MHPG are more likely to show the cognitive features of learned helplessness.
Abstract 2623: Right Ventricular Hypertrophy in Monocrotaline-induced Pulmonary Hypertension is Associated with Impaired Oxidative Metabolism and Action Potential Prolongation
Authors: Lin Piao, Dalia Urboniene, Hannah J Zhang, Peter T Toth, Jalees Rehman, Stephen L Archer
Journal: Circulation (2008)

Introduction: Right ventricular hypertrophy (RVH) and right ventricular failure are major determinants of prognosis and functional state in pulmonary artery hypertension (PAH). We previously found a mitochondrial metabolic shift in the pulmonary circulation in clinical as well as experimental PAH that includes a shift from oxidation to glycolysis, decreased production of reactive oxygen species (ROS) and normoxic activation of HIF-1α and decreased expression of voltage-gated potassium channels. In this study, we hypothesize that during RVH there is a similar metabolic shift in the RV characterized by impaired mitochondrial respiration and that the resulting electrical remodeling causes action potential prolongation. Methods and Results: PAH was induced in Sprague-Dawley rats by single injection of monocrotaline (60mg/Kg). At 3 weeks, PAH was confirmed by a shortened pulmonary artery acceleration time vs controls (13.8±0.7 vs 36.2±0.2 msec, P &lt; 0.001) as determined by Doppler Echo. RVH was also evident, with a thicker right ventricular free wall in monocrotaline vs control hearts (1.3±0.1 vs 0.9±0.0 mm, P &lt; 0.001 vs control) as assessed by two-dimensional and M-mode Echo. Oxygen consumption of right ventricular tissues (140mg samples) was measured using high-resolution respirometry. In an RV Langendorff model, RV systolic pressure (RVSP) and RV monophasic action potential duration (MAP) were measured. The ratio of RV/LV+S weight increased to 2 fold with monocrotaline (P &lt; 0.001). RVSP in MCT group was increased to 50.9±10.6 vs 21.3±2.7 mmHg, P &lt; 0.05). RV O2-consumption in RVH was significantly reduced vs control [144.1±37.6 vs 277.0±27.4 pmol/(sec*ml), P &lt; 0.05]. The duration of 90% and 75% repolarization of MAP (MAPD90 and MAPD75) was markedly prolonged in RVH (145% and 136% vs controls; P &lt; 0.001, P &lt; 0.05, respectively). Importantly, MAPD90 increased in direct proportion to the severity of PAH, as measured by RVSP. Conclusions: RVH was associated with impaired RV metabolism as evidenced by reduced O2 consumption. This metabolic shift was associated with significant action potential prolongation in the RV. The consequences of this ionic remodeling for arrhythmogenisis and contractility remain to be determined.
Abstract 269: A “Front-Loaded” Rapid Response Team Decreases Non-ICU Arrests and Overall Hospital Mortality
Authors: Morgan C Ludington, Patricia Graham, Brenna Lawrence, Rebecca Sell, Ruchika D Husa, Anush Minokadeh, Daniel Davis
Journal: Circulation (2011)

Background: In-hospital cardiopulmonary arrest (CPA) is characterized by progressive hypoxemia and hypotension leading to bradyasystole. Rapid response teams (RRTs) are designed to prevent non-ICU CPA through early detection and therapeutic intervention. However, existing evidence has not consistently demonstrated benefit to RRT programs. Objective: To explore the effectiveness of a “front-loaded” RRT program to decrease non-ICU CPA and overall hospital mortality. Methods: This study was conducted in two urban university hospitals from 2005 to 2011. In 2007, our hospitals implemented RRT as part of the Advanced Resuscitation Training (ART) program. Our RRT program is “front-loaded” in that charge nurses from each inpatient unit undergo training as RRT members, and all inpatient staff receive annual training in RRT concepts. To evaluate overall effectiveness of RRT, we compared the incidence of non-ICU CPA (per 1,000 patient discharges) before and after program implementation. The incidence of ICU CPA as well as overall hospital mortality were also reported. In addition, the overall number of RRT versus code blue activations for each individual inpatient unit were compared using linear regression. Finally, the annual change in RRT versus code blue activations for each inpatient unit were also compared. Results: A total of 546 CPAs were observed from 2005-11; a total of 725 RRT activations were observed from 2007-11. The incidence of non-ICU CPA decreased while the incidence of ICU CPA remained unchanged follow RRT program implementation. Overall hospital mortality also decreased over the study period (2.12% to 1.74%, p&lt;0.001). Inpatient units with a greater number of code blue activations also had more RRT activations (r=0.17, p=0.242). However, units with a year-over-year increase in RRT activations experienced a decrease in code blue activations, while units with a decrease in RRT activations experienced an increase in code blue activations (r=-0.68, p&lt;0.001). Conclusion: A front-loaded RRT program decreases the incidence of non-ICU CPA and overall hospital mortality.
Abstract 15490: Prognostic Value and Accuracy of Vasodilator Stress Cardiac MRI and 320-Row Coronary CTA
Authors: Marcus Y Chen, W. P Bandettini, Sujata M Shanbhag, Sujethra Vasu, Oscar J Booker, Steve W Leung, Joel R Wilson, Peter Kellman, Li-Yueh Hsu, Andrew E Arai
Journal: Circulation (2011)

Objective: To assess the prognostic value and accuracy of vasodilator stress cardiac MRI (CMR) and 320-row coronary CTA in patients with suspected coronary artery disease (CAD). Background: Vasodil...
Pattern of recurrence of illness after recovery from an episode of major depression: a prospective study
Authors: M Maj, F Veltro, R Pirozzi, S Lobrace, L Magliano
Journal: American Journal of Psychiatry (1992)

This study assessed prospectively the pattern of recurrence of illness after recovery from an episode of major depression.Seventy-two patients who had recovered from an episode of primary, nonbipolar, nonpsychotic major depression were evaluated bimonthly with the Comprehensive Psychopathological Rating Scale for a period ranging from 20 to 108 months (median = 66 months). New ("prospective") episodes were ascertained with a structured diagnostic interview. The probabilities of remaining well after the index episode and after the first prospective episode were assessed by the life-table method. The severity and duration of prospective episodes and the index episode were compared by linear regression analysis.The probability of remaining well after recovery from the index episode was 76% at 6 months, 63% at 1 year, and 25% at 5 years. The risk of recurrence was lower among patients receiving prophylactic treatment with antidepressants and/or lithium and among those with histories of fewer than three previous episodes. The probability of remaining well was significantly lower 2 years after the first prospective episode than 2 years after the index episode. A pattern of increasing severity from the index episode to the first, second, and third prospective episodes was observed and was not affected by treatment.Major depression has a high rate of recurrence, even when bipolar and psychotic cases are excluded. The highest rate is observed during the first months after recovery from an episode. Prophylactic drug treatment reduces the risk of recurrence but apparently does not affect the trend toward increasing severity of subsequent episodes.
Abstract 1951: Histamine H1 Receptor is Required for Atherogenesis
Authors: Izabela Rozenberg, Pavani Mocharla, Burkhard Becher, Janin Hofmann, Alexander Akhmedov, Jan Boren, Thomas F Lüscher, Felix C Tanner
Journal: Circulation (2008)

Background and aims: Histamine is an endogenous amine that plays a critical role as a mediator of inflammation and allergic response. Most of the proinflammatory actions of histamine are mediated via H1 receptor (H1R). Although histamine affects numerous inflammatory processes, its relevance in atherogenesis remains unknown. Methods: We used both a pharmacological and a genetic approach to modulate H1R- or H2 receptor (H2R) -signalling in a mouse model of atherosclerosis. Apolipoprotein E (ApoE)-deficient mice were treated for 12 weeks either with the H1R antagonist mepyramine, the H2R antagonist ranitidine, or placebo. In parallel, we compared H1R −/− ApoE −/− and H2R −/− ApoE −/− to ApoE single knockout mice after 12 weeks of stimulation with high cholesterol diet (Clinton-Cybulski diet, 1.25% cholesterol). Results: ApoE-deficient animals treated with mepyramine, but not ranitidine, exhibited significantly reduced aortic plaque area compared with placebo-treated mice. Similarly, genetic deficiency of H1 receptor in ApoE−/− mice resulted in a 60% decrease in aortic plaque formation. Level of plasma lipids as well as permeability of the vessel wall was not affected by the absence of H1R. H1R-deficient animals showed significantly decreased levels of CCL5 and CD40 in the aorta. In parallel, atherosclerotic plaques of these animals revealed significantly decreased infiltration with macrophages and T-helper cells. Moreover, reduced blood lymphocyte number, spleen size, and decreased production of splenic Th1-specific cytokines (CCL5, IL-2, and IFNγ) were observed in the absence of H1R. Interestingly, bone marrow transplantation revealed, that the presence of H1R on bone marrow-derived cells is irrelevant for both atherosclerotic plaque formation and regulation of spleen size. Conclusions: We conclude that blocking the H1 receptor leads to decreased atherogenesis due to indirect alteration of leukocyte function.
Abstract 15359: Alterations in Ephrin A1/EphA2 Signaling Causes Defects in the Migration of Senescent Human Cardiac Stem Cells
Authors: Polina Goichberg, Ramaswamy Kannappan, Yingnan Bai, Claudia Fiorini, Domenico D'Amario, Fumihiro Sanada, Ada Pesapane, Christian Arranto, Junghyun Kim, Luigi Anastasia, Narasimman Gurusamy, David A D'Alessandro, Robert E Michler, Hanqiao Zheng, Toru Hosoda, Marcello Rota, Jan Kajstura, Roberto Bolli, Piero Anversa, Annarosa Leri
Journal: Circulation (2011)

The male human heart loses 64x10^6 myocytes per year indicating that the formation of new cells derived from the differentiation of human cardiac stem cells (hCSCs) is not sufficient to counteract ...
Mipomersen, an Apolipoprotein B Synthesis Inhibitor, Reduces Atherogenic Lipoproteins in Patients With Severe Hypercholesterolemia at High Cardiovascular Risk
Authors: Gregory S. Thomas, William C. Cromwell, Shariq Ali, Wai Chin, JoAnn D. Flaim, Michael Davidson
Journal: Journal of the American College of Cardiology (2013)
A prospective observational clinical study involving an alternative cancer treatment, psorinum therapy, in treating stomach, gallbladder, pancreas, and liver cancers
Authors: A. Chatterjee, S. Bhattacharya, A. K. Chatterjee, J. Biswas, B. Mukhopadhyay
Journal: Journal of Clinical Oncology (2009)

3050 Background: The prospective observational clinical study was conducted to know the efficacy of an alternative cancer treatment, ‘psorinum therapy,‘ in treating liver, gall bladder, pancreatic, and stomach cancers. The primary outcome measures of the study were (1) to assess the radiological tumor response; (2) to assess how many participants survived at least 1 year, 2 years, 3 years, 4 years, and finally, 5 years after the beginning of the study. The secondary outcome measure of the study was to assess the side effects of the investigational anti-cancer drug (psorinum) if any. Methods: The drug psorinum (an alcoholic extract of scabies, scrub, slough, and pus cells) was administered orally at 0.01ml-0.02 ml/Kg body weight as a single dose in empty stomach per day and ongoing to all the participants along with allopathic and homeopathic supportive cares. Results: 158 histopathology or cytopathology proved participants (42 of stomach, 40 of gallbladder, 44 of pancreas, and 32 of liver cancers) were included in the final analysis at the end of the study. According to the AJCC/UICC TNM staging system, 7 (4.43%) of them diagnosed at stage II, 39 (24.68%) of them diagnosed at late stage II or early stage III and 112 (70.87%) of them diagnosed at late stage III or stage IV. According to the RECIST criteria, complete tumor response occurred in 28 (17.72%) cases and partial tumor response occurred in 56 (35.44%) cases. 126 (79.75%) of them survived at least 1 year, 99 (62.66%) of them survived at least 2 years, 87 (55.06%) of them survived at least 3 years, 76 (48.10%) of them survived at least 4 years, and 62 (39.24%) of them survived at least 5 years. These participants did not receive any other conventional or investigational cancer treatments. The participants report no side effects from the drug psorinum. Conclusions: Psorinum therapy is effective in treating stomach, gallbladder, pancreas, and liver cancers. Double-blinded randomized controlled clinical trial should be done for further investigation of this alternative cancer treatment. No significant financial relationships to disclose.
Soundings: Three puzzling cases
Authors: George Dunea
Journal: BMJ (2004)

The clinicopathological conference is a time honoured exercise in which a participant is given a clinical protocol and tries to make a diagnosis. It has been variously lauded as an instructive teaching exercise or derided as an unreal situation.

The cases are often puzzling. What, for example, is one to make of a wasted man, deathly pale, with web-like thin hair, exaggerated sensitivity to noise, odours, light, or touch, where the course of the disease fluctuates with intermittent agitation or depression?

Or what sudden epidemic illness would cause high fever, profuse generalised bleeding, and death within half an hour?

And what about a dishevelled 39 year old man with a history of alcohol and possibly opiate use, presenting with lethargy and confusion but remaining afebrile, becoming delirious and combative, and dying within four days.

The first two cases, products of Edgar Allan Poe's lugubrious imagination, defy diagnosis. The symptoms of the cadaverous looking man in The Fall of the House of Usher have been attributed, perhaps not too convincingly, to acute intermittent porphyria (JAMA 1989;261: 863-4 [PubMed]). One can only speculate what might have caused the hideous pestilence with “sharp pains, sudden dizziness, and then profuse bleeding at the pores with dissolution... the incidents of half an hour” (The Mask of the Red Death).

For the third case, a Dr Michael Benitez at one time suggested rabies. It is a case unsolved since 1849, when the patient boarded a train in Richmond, disappeared for five days, was found confused in a Baltimore tavern, dishevelled, in someone else's clothes, then taken to a city hospital, where he died delirious after several days. Delirium tremens, encephalitis, and malaria have been considered, but some think he was robbed and mugged. Others postulated that this being during an election, Poe (for it was the author himself) was drugged by a “repeater” gang and taken to vote at different polling booths, then abandoned.

There are further mysteries: firstly, the body was exhumed in 1875 and relocated, but there is speculation that the gravediggers dug up the wrong body; and secondly, for several years after 1949 an anonymous visitor would come on Poe's birthday and place a half bottle of Martel cognac on his grave.