tbuckley/cabot-search huggingface dataset:
Neuregulin-1β1 rapidly modulates nitric oxide synthesis and calcium handling in rat cardiomyocytes
Authors: Alessia Brero, Roberta Ramella, Amandine Fitou, Claudio Dati, Giuseppe Alloatti, Maria Pia Gallo, Renzo Levi
Journal: Cardiovascular Research (2010)

The ErbB–neuregulin-1β1 (Nrg1β1) pathway is required for cardiac development and exerts chronic effects on the postnatal adult heart. Long-term application of Nrg1β1 results in hypertrophy and protection against oxidative stress and cytotoxic agents. We performed experiments with acute Nrg1β1 treatment to find evidence for a further protective role due to rapid modulation of adult cardiomyocyte function. In confocal fluorimetric measurements, Nrg1β1 induced a calcium-independent increase in nitric oxide (NO) production in isolated adult rat ventricular myocytes (ARVCMs) that was blocked by the phosphoinositide-3-kinase (PI3K) inhibitor Wortmannin. Western blot analysis showed enhancement of endothelial nitric oxide synthase phosphorylation in Nrg1β1-treated ARVCMs, which was attenuated by Wortmannin. Nrg1β1 induced a significant increase in calcium transient amplitude (indo-1 ratiometric measurement) and accelerated the recovery of cytosolic calcium in the sarcoplasmic reticulum without affecting whole-cell L-type calcium current. Wortmannin or the protein kinase G inhibiting peptide (DT-2) abolished the increase in calcium transient amplitude and the acceleration of calcium recovery induced by Nrg1β1 treatment. Immunofluorescence analysis revealed that Nrg1β1 treatment increased phospholamban phosphorylation, and the effect was blocked by PI3K and protein kinase G inhibition. Caffeine-releasable sarcoplasmic reticulum calcium content was also higher during Nrg1β1 administration. Rapid activation of PI3K, endothelial nitric oxide synthase and protein kinase G and a consequent improvement in diastolic calcium can be added to established Nrg1 protective roles.
John L. Gollan, M.D., Ph.D., March 3, 1942‐January 6, 2015
Authors: Michael F. Sorrell
Journal: Hepatology (2015)

1University of NebraskaOmahaNE *Address reprint requests to: Michael F. Sorrell, M.D., Department of Surgery, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, NE 68198‐3280. E‐mail: [email protected]; fax: 402‐559‐5954.
Hyperplasia of Brunner's glands
Authors: J. F. Stokes, L. A. Turnberg, J. C. Hawksley
Journal: Gut (1964)

EDITORIAL SYNOPSIS The function of Brunner's glands in the duodenum has never been adequately defined and it is therefore particularly necessary to bring together any evidence which might relate to clinical syndromes.This paper records three patients with upper abdominal symptoms and apparent hyperplasia of these glands.
Excretion of administered and endogenous photobilirubins in the bile of the jaundice gunn rat.
Authors: M S Stoll, E A Zenone, J D Ostrow
Journal: Journal of Clinical Investigation (1981)

Radiolabeled photobilirubins, prepared in vitro by anaerobic illumination of [34C]bilirubin, were injected intravenously into homozygous jaundiced Gunn rats with an external bile fistula. With the animals kept in darkness, the labeled photobilirubins were excreted rapidly in bile. Photobilirubins IA and IB were excreted primarily as unconjugated bilirubin, whereas photobilirubin II was excreted primarily as photobilirubin II and not converted into bilirubin. Bile of Gunn rats given no exogenous pigments, but undergoing phototherapy, contained a large proportion of photobilirubin II and, if collected in liquid nitrogen, traces of photobilirubins I; neither was found in bile when these rats were kept in the dark. Because there is prior evidence that these rats were kept in the dark. Because there is prior evidence that these photobilirubins are isomers of bilirubin, these experiments indicate that the major mechanism of phototherapy is photoisomerization of bilirubin. Photobilirubin II is the unidentified major photoderivative described previously, whereas formation of photobilirubins IA and IB, and their reversion to bilirubin-IXalpha, account for the remarkably increased output of the parent pigment during phototherapy.
Transvenous Biventricular Defibrillation Halves Energy Requirements in Patients
Authors: Christian Butter, Eckhard Meisel, Juergen Tebbenjohanns, Lothar Engelmann, Eckart Fleck, Bernd Schubert, Stephen Hahn, Dietrich Pfeiffer
Journal: Circulation (2001)

Defibrillation thresholds (DFT) with standard implantable cardioverter-defibrillator leads in the right ventricle (RV) may be determined by weak shock field intensity in the myocardium of the left ventricle (LV). Adding a shocking electrode in a coronary vein on the middle of the LV free wall, thereby establishing biventricular defibrillation, substantially reduced defibrillation requirements in animals. We investigated the feasibility of this approach in 24 patients receiving an implantable cardioverter-defibrillator using a prototype over-the-wire temporary LV defibrillation lead.The LV lead was inserted through the coronary sinus, using a guide catheter and guidewire, into a posterior or lateral coronary vein whose location was determined by retrograde venography. Paired DFT testing compared a standard system (RV to superior vena cava plus can emulator [SVC+Can], 60% tilt biphasic shock) to a system including the LV lead. The biventricular system was tested with a dual-shock waveform (20% tilt monophasic shock from LV-->SVC+Can, then 60% tilt biphasic shock from RV-->SVC+Can). Twenty patients completed DFT testing. Venography and LV lead insertion time was 46+/-40 minutes. The biventricular system reduced mean DFT by 45% (8.9+/-1.1 J versus 4.9+/-0.5 J, P<0.001). Twelve patients (60%) had a standard system DFT >/=8 J, and the biventricular system gave a lower DFT in all patients. There were no adverse events related to the use of the LV lead, which was removed after testing.Internal defibrillation using a transvenously inserted LV lead is feasible, produces significantly lower DFTs, and seems safe under the conditions tested. Biventricular defibrillation may be a useful option for reducing DFTs or could be added to an LV pacing lead for heart failure.
Response to Rodríguez-Segade et al. and Leslie and Kilpatrick
Authors: David M. Nathan
Journal: Diabetes Care (2008)

Rodriguez-Segade et al. (1) question the clinical usefulness of the estimated average glucose (eAG) developed by the A1C-Derived Average Glucose (ADAG) Study (2). They note that although the study met the a priori–specified criterion for acceptability (≥90% of subject values within 15% of the regression line between A1C and calculated mean glucose), the variability of the estimate makes the equation clinically useless. Furthermore, they state, without any supporting evidence, that the assumption that “A1C depends exclusively on average plasma glucose—is not justified.”

Leslie and Kilpatrick (3) remarkably resort to the Heisenberg uncertainty principle of quantum physics (which states the uncertainty of simultaneously measuring the position and momentum of a particle, owing in part to the perturbation of the particle as part of the measurement) to point out …
KSHV-encoded CC chemokine vMIP-III is a CCR4 agonist, stimulates angiogenesis, and selectively chemoattracts TH2 cells
Authors: Johnny T. Stine, Christi Wood, Mark Hill, Angela Epp, Carol J. Raport, Vicki L. Schweickart, Yoshio Endo, Takuma Sasaki, Graham Simmons, Chris Boshoff, Paul Clapham, Yuan Chang, Patrick Moore, Patrick W. Gray, David Chantry
Journal: Blood (2000)
Dehydroepiandrosterone Can Inhibit the Proliferation of Myeloma Cells and the Interleukin-6 Production of Bone Marrow Mononuclear Cells from Patients with Myeloma
Authors: Shangqin Liu, Hideaki Ishikawa, Fu-Jun Li, Zi Ma, Ken-ichiro Otsuyama, Hideki Asaoku, Saeid Abroun, Xu Zheng, Naohiro Tsuyama, Masanori Obata, Michio M. Kawano
Journal: Cancer Research (2005)

Abstract The serum levels of an adrenal sex hormone, dehydroepiandrosterone sulfate (DHEA-S), are significantly more decreased in human myelomas compared with the reduction brought by physiologic decline with age. In order to clarify the effect of DHEA on myeloma cells, we investigated whether DHEA and DHEA-S could inhibit interleukin-6 (IL-6) production of bone marrow mononuclear cells and the proliferation of myeloma cells from patients with myeloma. DHEA-S and DHEA suppressed IL-6 production from a bone marrow stromal cell line, KM-102, as well as in bone marrow mononuclear cells from patients with myeloma. Furthermore, DHEA inhibited in vitro growth of the U-266 cell line and primary myeloma cells from the patients, as well as the in vivo growth of U-266 cells implanted i.p. in severe combined immunodeficiency-hIL6 transgenic mice. DHEA up-regulated the expression of peroxisome proliferator–activated receptor (PPAR), PPAR β, but not PPARγ or PPARα, and the expression of IκBα gene in myeloma cells and bone marrow stromal cells, which could explain the suppressive effect of DHEA on IL-6 production through the down-regulation of NF-κB activity. Therefore, these data revealed that DHEA-S, as well as DHEA, had a direct effect on myeloma and bone marrow stromal cells to inhibit their proliferation and IL-6 production, respectively.
Long-term treprostinil in pulmonary arterial hypertension: is the glass half full or half empty?
Authors: S. Provencher
Journal: European Respiratory Journal (2006)

Pulmonary arterial hypertension (PAH) has traditionally been considered as an inevitably fatal disease. In the 1980s, a national registry funded by the National Institutes of Health (NIH) described the natural history of idiopathic PAH 1. The median survival was <3 yrs and prognosis was mostly related to baseline functional capacity and pulmonary haemodynamics. In case series, the long-term outcome of patients with PAH associated with connective tissue disease, portal hypertension and HIV infection appeared to be even worse 2. This was before the era of PAH-specific therapies. In the last decade, significant advances in the current understanding of the disease have led to the development of new specific treatments. In 1996, a placebo-controlled trial demonstrated significant survival benefit with i.v. epoprostenol in idiopathic PAH patients 3. Several other therapies, including prostacyclin analogues, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors, were subsequently evaluated in short-term randomised placebo-controlled trials. These studies demonstrated improvements in pulmonary haemodynamics, exercise capacity and quality of life 4–6. This new era of therapy has clearly brought enthusiasm among physicians. From a clinician's perspective, the glass has been half filled.

Treprostinil s.c. was evaluated in a large randomised placebo-controlled trial involving 470 PAH patients randomised to either s.c. treprostinil or placebo 7. Over a 12-week period, s.c. treprostinil improved patients’ exercise capacity, PAH-related symptoms and haemodynamics. The median placebo-corrected increase in 6-min walking distance was 16 m, with greater improvements in severely ill patients at baseline and in those who could tolerate the highest doses. Unfortunately, this short-term trial, as with others, was underpowered and not designed to detect survival benefit. Indeed, the most ill patients are no longer entered into placebo-controlled …
Echocardiographic method for the estimation of pulmonary artery pressure in chronic lung disease.
Authors: M J Boyd, I P Williams, C W Turton, N Brooks, G Leech, F J Millard
Journal: Thorax (1980)

The prognostic implications of pulmonary hypertension in chronic lung disease, and the difficulty in establishing its severity without cardiac catheterisation, indicate the need for a reliable non-invasive method of assessing the pulmonary artery pressure. It is likely that the time taken by the right ventricle to generate a sufficiently high pressure to open the pulmonary valve will increase progressively as the pulmonary arterial diastolic pressure rises. Therefore, the time interval between closure of the tricuspid valve and opening of the pulmonary valve has been obtained by high-speed echocardiographic recordings of the tricuspid and pulmonary valves in a group of 17 patients with chronic lung disease. Each patient underwent right heart catheterisation immediately after the echocardiographic examination so that the pulmonary arterial diastolic pressure could be obtained directly. A range for the group from 15 mmHg (2.0 kPa) to 45 mmHg (6.0 kPa) was observed. The linear correlation between the measured diastolic pressure and time interval from the tricuspid valve closure to pulmonary valve opening was highly significant (r = 0.94, p = less than 0.001) and the scatter was relatively small. It is therefore suggested that this time interval, obtained non-invasively by echocardiography, can be used as an index of the severity of pulmonary hypertension associated with chronic lung disease.
Factors influencing compliance to PEF monitoring in asthma
Authors: Felicia Cora, Eugenia Buzoianu, Mariana Moiceanu, Doina Anca Plesca
Journal: European Respiratory Journal (2013)

BACKGROUND: PEF measurement is an usefull tool for asthma control monitoring, but the need to undergo daily measurement for a relatively long time decreases compliance to this method.  The aim of this study is to reveal the impact on compliance to PEF monitoring of certain factors more often encounted in clinical practice like age, severity of exacerbation and parents availability as supervisors.  METHOD: A prospective study lasting 1 year including 30 asthmatic children aged 6 to 17 years old was conducted. Children began asthma monitoring using PEF (twice daily measurements) following ER visit or/and admission in our clinic for asthma exacerbation. Each child was scheduled to medical check-up at 2 weeks, 1 month, 2 months and 3 months after discharge and associated factors were counted.  RESULTS: 1 child completed the 3 months follow up; 4 children completed 2 months, 16 completed 1 month and 6 completed 2 weeks of follow up; 3 children had no compliance. 100% in the no compliance group and 83,3 % in the 2 weeks group had all 3 factors that decrease compliance, 62,5% in the 1 month group had at least 2 factors, 25% in the 2 months group had 1 factor and the child who completed 3 months follow up had no factor.  CONCLUSION: Number of factors and follow up lenght are in inverse ratio to compliance in asthma monitoring, patients requiring additional motivation to remain comitted to asthma control plan.
Response to Letter Regarding Article, “Histone Deacetylation Inhibition in Pulmonary Hypertension: Therapeutic Potential of Valproic Acid and Suberoylanilide Hydroxamic Acid”
Authors: Lan Zhao, Chien-Nien Chen, Nabil Hajji, Eduardo Oliver, Emanuele Cotroneo, John Wharton, Martin R. Wilkins, Daren Wang, Min Li, Kurt R. Stenmark, Timothy A. McKinsey, Peter Buttrick
Journal: Circulation (2013)
The Hand as a Mirror of Systemic Disease
Authors: A. St.J. Dixon
Journal: Annals of the Rheumatic Diseases (1964)

The human hand is a fascinating subject, an actor of many roles and disguises: the man in miniature, revealing its owner's story.Here is a book which sets out to teach us how best to examine it.This book has had an immediate appeal to everyone who has seen it.All doctors are, from time to time, called upon to see patients quickly, when facilities and time for a full general examination are missing.A guide to what could be regarded as "how-not-to-miss-systemic-diseasewithout-undressing-the-patient" will obviously have a wide market.The book is excellently printed, beauti- ully bound, and most of the pictures are clear and com-
Health Is Still Social: Contemporary Examples in the Age of the Genome
Authors: Timothy H Holtz, Seth Holmes, Scott Stonington, Leon Eisenberg
Journal: PLoS Medicine (2006)

In 1999, Leon Eisenberg wrote an essay entitled, “Does social medicine still matter in an era of molecular medicine?” [1]. Anticipating the scientific discussion that would accompany the complete mapping of the human genome, followed by hubristic predictions of an end to disease through the introduction of gene-based therapy, Eisenberg reminded his readers of the inherent social basis of disease causation. “The developments in molecular biology highlight the salience of the social environment and underscore the urgency to rectify inequity and injustice. All medicine is inescapably social,” he wrote.

In this Essay, we revisit those concerns and expand them to discuss the current state of scholarship on the social causes of, experiences of, and responses to disease. We contend that social medicine is as important now as it has ever been. The field of social medicine includes various social and cultural studies of health and medicine [2], and in this article, we will focus on one domain of these studies—the social roots of disease—to illustrate the contemporary importance of social medicine.
Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial
Authors: Nicolino Ruperto, Daniel J Lovell, Pierre Quartier, Eliana Paz, Nadina Rubio-Pérez, Clovis A Silva, Carlos Abud-Mendoza, Ruben Burgos-Vargas, Valeria Gerloni, Jose A Melo-Gomes, Claudia Saad-Magalhães, Flavio Sztajnbok, Claudia Goldenstein-Schainberg, Morton Scheinberg, Immaculada Calvo Penades, Michael Fischbach, Javier Orozco, Philip J Hashkes, Christine Hom, Lawrence Jung, Loredana Lepore, Sheila Oliveira, Carol A Wallace, Leonard H Sigal, Alan J Block, Allison Covucci, Alberto Martini, Edward H Giannini
Journal: The Lancet (2008)
Trifluoperazine, an Antipsychotic Agent, Inhibits Cancer Stem Cell Growth and Overcomes Drug Resistance of Lung Cancer
Authors: Chi-Tai Yeh, Alexander T. H. Wu, Peter M.-H. Chang, Kuan-Yu Chen, Chia-Ning Yang, Shuenn-Chen Yang, Chao-Chi Ho, Chun-Chi Chen, Yu-Lun Kuo, Pei-Ying Lee, Yu-Wen Liu, Chueh-Chuan Yen, Michael Hsiao, Pei-Jung Lu, Jin-Mei Lai, Liang-Shun Wang, Chih-Hsiung Wu, Jeng-Fong Chiou, Pan-Chyr Yang, Chi-Ying F. Huang
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Cancer stem cell (CSC) theory has drawn much attention, with evidence supporting the contribution of stem cells to tumor initiation, relapse, and therapy resistance.To screen drugs that target CSCs to improve the current treatment outcome and overcome drug resistance in patients with lung cancer.We used publicly available embryonic stem cell and CSC-associated gene signatures to query the Connectivity Map for potential drugs that can, at least in part, reverse the gene expression profile of CSCs. High scores were noted for several phenothiazine-like antipsychotic drugs, including trifluoperazine. We then treated lung CSCs with different EGFR mutation status with trifluoperazine to examine its anti-CSC properties. Lung CSCs resistant to epidermal growth factor receptor-tyrosine kinase inhibitor or cisplatin were treated with trifluoperazine plus gefitinib or trifluoperazine plus cisplatin. Animal models were used for in vivo validation of the anti-CSC effect and synergistic effect of trifluoperazine with gefitinib.We demonstrated that trifluoperazine inhibited CSC tumor spheroid formation and down-regulated the expression of CSC markers (CD44/CD133). Trifluoperazine inhibited Wnt/β-catenin signaling in gefitinib-resistant lung cancer spheroids. The combination of trifluoperazine with either gefitinib or cisplatin overcame drug resistance in lung CSCs. Trifluoperazine inhibited the tumor growth and enhanced the inhibitory activity of gefitinib in lung cancer metastatic and orthotopic CSC animal models.Using in silico drug screening by Connectivity Map followed by empirical validations, we repurposed an existing phenothiazine-like antipsychotic drug, trifluoperazine, as a potential anti-CSC agent that could overcome epidermal growth factor receptor-tyrosine kinase inhibitor and chemotherapy resistance.
Automated quantitation of circulating neutrophil and eosinophil activation in asthmatic patients
Authors: M. J Leckie
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Asthma has been associated with eosinophil activation, measured in serum, sputum, bronchoalveolar lavage (BAL) fluid, and urine. A whole blood automated method was developed to assess eosinophil and neutrophil activity in terms of peroxidase content and cell morphology using the Bayer haematology analyser. The method was applied to an in vitro stimulation model when fMLP was added to whole blood and the samples were then analysed for changes in granularity and shape. In addition, cells stimulated with interleukin (IL)-8 were examined by electron microscopy. <h3>METHODS</h3> A cross sectional analysis was performed on venous blood from non-atopic, non-asthmatic normal subjects (n = 37), mild (n = 46) and symptomatic (n = 22) asthmatic patients on inhaled β<sub>2</sub> agonist only, and more severe asthmatic patients (n = 17) on inhaled and oral corticosteroid therapy. Samples were analysed by the haematology analyser and peroxidase leucograms gated using the WinMDI software program. <h3>RESULTS</h3> There were significant differences in the amount of light scatter by the neutrophil populations in the symptomatic (p = 0.007) and severe asthmatic (p = 0.0001) groups compared with the control group. However, abnormalities in eosinophil populations were not observed. In vitro activation of whole blood with fMLP caused similar changes in neutrophil light scatter, suggesting that neutrophil activation is present in peripheral blood of symptomatic asthmatic patients. IL-8 caused a change in shape of the neutrophils seen using transmission electron microscopy. <h3>CONCLUSIONS</h3> Evidence of neutrophil activation can be seen in whole blood from patients with asthma using a novel automated method. This may potentially be applied to other inflammatory diseases.
THE IMPLEMENTATION OF TEAM BALL SPORT INJURY PREVENTION EXERCISE PROGRAMMES: A SYSTEMATIC REVIEW EMPLOYING THE RE-AIM FRAMEWORK
Authors: J O'Brien, CF Finch
Journal: British Journal of Sports Medicine (2014)

Background Recent published studies on injury prevention exercise programmes (IPEPs) in team ball sports support the protective effect of these interventions, but also highlight that achieving adequate compliance is challenging. A key process in enhancing the ultimate impact of team ball sport IPEPs is identifying the specific implementation components which influence their adoption, execution and maintenance. Objectives To assess the reporting of specific implementation components in team ball sport IPEP trials, against the components of the Reach Efficacy Adoption Implementation Maintenance (RE-AIM) framework. To evaluate the applicability of the RE-AIM framework to reviewing published literature in this context. Methods 6 electronic databases were systematically searched from inception to December 2012 for papers reporting team ball sport IPEP trials. All eligible papers were evaluated for the reporting of individual RE-AIM components using the RE-AIM Model Dimension Items Checklist (RE-AIM MDIC). The level of agreement and the process of reaching consensus between reviewers were recorded. Results A total of 60 papers, reporting 52 unique intervention trials, met eligibility criteria. On average, the individual RE-AIM items were reported in 22% of the 52 trials (range 0–100%). The RE-AIM MDIC dimension of Efficacy had the highest mean percentage (58%) level of reporting across trials. The lowest mean percentages (range 0–7%) were for the RE-AIM MDIC dimensions related to Adoption and Maintenance. The level of agreement across all trials between reviewers using the RE-AIM MDIC ranged from 81% to 91%. Conclusion Information on the specific implementation components of team ball sport IPEPs in published studies is scarce. In particular, major knowledge gaps exist regarding the adoption and maintenance of these programmes. The RE-AIM MDIC can be successfully applied to reviewing literature in this context.