tbuckley/cabot-search huggingface dataset:
Dopamine Agonists and the Risk of Cardiac-Valve Regurgitation
Authors: René Schade, Frank Andersohn, Samy Suissa, Wilhelm Haverkamp, Edeltraut Garbe
Journal: New England Journal of Medicine (2007)

Case reports and echocardiographic studies suggest that the ergot-derived dopamine agonists pergolide and cabergoline, used in the treatment of Parkinson's disease and the restless legs syndrome, may increase the risk of cardiac-valve regurgitation.
Childhood cancer survival in Europe 1999–2007: results of EUROCARE-5—a population-based study
Authors: Gemma Gatta, Laura Botta, Silvia Rossi, Tiiu Aareleid, Magdalena Bielska-Lasota, Jacqueline Clavel, Nadya Dimitrova, Zsuzsanna Jakab, Peter Kaatsch, Brigitte Lacour, Sandra Mallone, Rafael Marcos-Gragera, Pamela Minicozzi, Maria-José Sánchez-Pérez, Milena Sant, Mariano Santaquilani, Charles Stiller, Andrea Tavilla, Annalisa Trama, Otto Visser, Rafael Peris-Bonet
Journal: The Lancet Oncology (2013)
Dietary Patterns and Longevity
Authors: Lawrence J. Appel
Journal: Circulation (2008)

scientific literature on diet and health is large and burgeoning.Until now, researchers have focused predominantly on the effects of individual nutrients and sometimes foods, but rarely on dietary patterns.Outcomes are often biomarkers, risk factors, or morbidity.Studies with total mortality as an outcome are uncommon, in large part because the sample size must be extremely large and/or the duration of follow-up long.Nonetheless, such studies are important because mortality as an outcome has unequivocal clinical relevance.In this issue of Circulation, Heidemann and colleagues 1 document the relationship of 2 dietary patterns with total and cause-specific mortality.
Role of IL-1 in renal ischemic reperfusion injury.
Authors: M Haq, J Norman, S R Saba, G Ramirez, H Rabb
Journal: Journal of the American Society of Nephrology (1998)

Interleukin-1 (IL-1) is a central component of many acute inflammatory processes. Blocking IL-1 receptor (IL-1R) with IL-1R antagonist (IL-1Ra) has attenuated ischemic reperfusion injury in brain, heart, and liver models. However, the role of IL-1 in renal ischemic reperfusion injury (IRI) is not known. Therefore, the role of IL-1 in renal IRI was evaluated using the complementary approaches of IL-1R blockade in wild-type mice in addition to the study of renal IRI in IL-1R knockout (KO) mice. Ischemia was induced by bilateral renal pedicle clamping for 30 min. IL-1Ra was administered at 10 mg/kg every 4 h, high doses that have been protective in previous organ injury models in mice. IL-1R KO animals, previously characterized as insensitive to IL-1, had the absence of IL-1R1 confirmed by DNA blots. IL-1Ra, IL-1R KO, and control groups had similar elevations of blood urea nitrogen (114 +/- 13, 133 +/- 11, and 120 +/- 11 mg/dl) and serum creatinine (1.7 +/- 0.3, 2.1 +/- 0.2, and 1.6 +/- 0.3 mg/dl) 24 h after ischemia. Furthermore, acute tubular necrosis scores were also similar in IL-1Ra-treated mice (3.0 +/- 0.3), IL-1R KO mice (2.7 +/- 0.3), and control mice (3.1 +/- 0.2). However, both IL-1Ra and IL-1R KO groups, compared with control animals, developed significantly less infiltration of polymorphonuclear leukocytes per 10 high-power fields in postischemic renal tissue (1111 +/- 228 and 967 +/- 198 versus 1820 +/- 190, P < 0.05). In contrast to the comparable renal functions at 24 h, recovery of renal function was significantly accelerated in the IL-1R KO group compared with control at both 48 (P < 0.05) and 72 (P < 0.05) h. Recovery in the IL-1Ra group was similar to that in the control animals. These data demonstrate that IL-1 is unlikely to be beneficial in the recovery of renal function after ischemia and may play a deleterious role.
Plasma lysophosphatidic acid levels and hepatocellular carcinoma
Authors: Hitoshi Ikeda, Kenichiro Enooku, Ryunosuke Ohkawa, Kazuhiko Koike, Yutaka Yatomi
Journal: Hepatology (2012)

We read with interest the article by Mazzocca et al.,1 showing that serum lysophosphatidic acid (LPA) levels are increased in hepatocellular carcinoma (HCC) patients correlated with tumor burden, while not enhanced in cirrhosis patients. However, we think that their LPA values in serum samples need to be carefully evaluated, because of some technical issues in the measurement of LPA levels in blood samples. First, because LPA is released from platelets, LPA has been measured in plasma but not in serum when evaluating its clinical significance.2, 3 Second, as we previously demonstrated,4 LPA levels in plasma samples are markedly increased after sample preparation unless the temperature is kept under strict control, potentially because the synthetic enzyme autotaxin (ATX) and the substrate lysophosphatidyl choline coexist in plasma samples to abundantly produce LPA. LPA was once reported as a biomarker of ovarian cancer,2 but contrary data were later demonstrated, in which a distinct sampling of plasma may explain this discrepancy.3 Indeed, LPA levels in serum reported by Mazzocca et al. were approximately 10 times higher than the previously reported LPA levels in plasma.2, 3 If their LPA values in serum were increased after sampling similarly in each sample, plasma LPA levels might be correlated with HCC burden as reported. To clarify this, we have newly measured plasma LPA levels in HCC patients, and found that they were not correlated with tumor burden, as shown in Fig. 1. Moreover, plasma LPA levels in HCC patients (0.12 ± 0.09 mM, mean ± SD, n = 21), were not different from the previously reported levels in non-HCC patients with chronic hepatitis C (0.10 ± 0.05 mM).5 Although Mazzocca et al. reported no enhancement of serum LPA levels in cirrhosis patients, we5 and others6 previously showed that plasma LPA levels and serum ATX activity were increased in chronic liver diseases in association with fibrosis and cholestatic pruritus, from which HCC frequently arises. Collectively, a role of LPA in HCC should be cautiously analyzed. Plasma LPA levels and HCC burden. Plasma LPA levels, measured in 21 HCC patients (13 males and 8 females; 2 patients with chronic hepatitis B, 15 with chronic hepatitis C, and 4 with non-B non-C chronic liver disease), were not significantly correlated with HCC burden as evaluated by RECIST (Response Evaluation Criteria in Solid Tumors; Spearman rank, r = 0.158, P = 0.4937). This study was approved by the Institutional Research Ethics Committee and informed consent was obtained for the use of the samples. Hitoshi Ikeda M.D., Ph.D.* , Kenichiro Enooku M.D. Ph.D.* , Ryunosuke Ohkawa Ph.D.*, Kazuhiko Koike M.D., Ph.D. , Yutaka Yatomi M.D., Ph.D.*, * Department of Clinical Laboratory Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Antivascular Therapy for Orthotopic Human Ovarian Carcinoma through Blockade of the Vascular Endothelial Growth Factor and Epidermal Growth Factor Receptors
Authors: Premal H. Thaker, Sertac Yazici, Monique B. Nilsson, Kenji Yokoi, Rachel Z. Tsan, Junqin He, Sun-Jin Kim, Isaiah J. Fidler, Anil K. Sood
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We determined whether the administration of the tyrosine kinase inhibitor, AEE788, which targets the epidermal growth factor receptor and the vascular endothelial growth factor receptor, alone or in combination with paclitaxel, can inhibit progressive growth of human ovarian carcinoma in the peritoneal cavity of female nude mice. Experimental Design: Western blot analysis and immunohistochemical analysis identified the optimal dose and schedule of AEE788 therapy. In several different experiments, paclitaxel-sensitive and paclitaxel-resistant human ovarian carcinoma cells were injected into the peritoneal cavity of nude mice. Seven days later, treatment with saline (control), AEE788 alone, paclitaxel alone, or a combination of AEE788 and paclitaxel began and continued for 45 days when the mice were necropsied. In independent survival experiments, the mice were necropsied when they became moribund. Results: Oral administration of AEE788 inhibited phosphorylation of the epidermal growth factor receptor and vascular endothelial growth factor receptor for up to 48 hours. Treatment with AEE788 plus paclitaxel significantly reduced tumor weight and increased survival of mice implanted with paclitaxel-sensitive cell lines compared with control mice or mice treated with AEE788 alone or paclitaxel alone. In mice implanted with paclitaxel-resistant cells, the combination therapy also significantly reduced tumor weight but did not prolong survival. The combination therapy induced apoptosis of both tumor cells and tumor-associated endothelial cells. Conclusions: The administration of AEE788 and paclitaxel inhibits the progression of human ovarian carcinoma in the peritoneal cavity of female nude mice, in part, by inducing apoptosis of tumor-associated endothelial cells.
Allergy to furry animals: New insights, diagnostic approaches, and challenges
Authors: Jon R. Konradsen, Takao Fujisawa, Marianne van Hage, Gunilla Hedlin, Christiane Hilger, Jörg Kleine-Tebbe, Elizabeth C. Matsui, Graham Roberts, Eva Rönmark, Thomas A.E. Platts-Mills
Journal: Journal of Allergy and Clinical Immunology (2014)
Pharmacological approaches to reperfusion therapy
Authors: O. Morel, T. Perret, N. Delarche, J.-N. Labeque, B. Jouve, M. Elbaz, C. Piot, M. Ovize
Journal: Cardiovascular Research (2012)

Despite the fact that numerous clinical trials investigating infarct size have been completed over the last two to three decades, the methods for treating lethal reperfusion injury efficiently have only become established very recently. After several years of accumulating evidence in experimental preparations that lethal reperfusion injury might exist, the description of the phenomenon of ischaemic post-conditioning in animal models has fully convinced us of the existence and importance of irreversible myocardial damage occuring after reflow. Transfer to the clinics was possible in small phase II trials, provided care was taken to assess the determinants of infarct size and, most importantly, to consider the timing of drug administration with respect to the time of reflow. Technical questions remain to be resolved regarding the assessment of the area at risk in the difficult setting of emergency care for reperfusion therapy. Nevertheless, convincing pharmacological trials are being performed that mark the start of a new era that will, in the future, improve the prognosis of patients with ST-segment elevation myocardial infarction through the prevention of lethal myocardial reperfusion injury. At present, while erythropoietin and adenosine have not proved efficient for alleviation of lethal reperfusion injury, a significant benefit has been reported for cyclosporin and exenatide. New pharmacological agents need to be identified and tested in phase II trials. In the meantime, clinical outcome studies are currently being conducted for cyclosporin.
Mesenchymal stem cell therapy in proteoglycan induced arthritis
Authors: J F Swart, S de Roock, F M Hofhuis, H Rozemuller, T van den Broek, P Moerer, F Broere, F van Wijk, W Kuis, B J Prakken, A C M Martens, N M Wulffraat
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To explore the immunosuppressive effect and mechanism of action of intraperitoneal (ip) and intra-articular (ia) mesenchymal stem cell (MSC) injection in proteoglycan induced arthritis (PGIA). <h3>Methods</h3> MSC were administered ip or ia after establishment of arthritis. We used serial bioluminescence imaging (BLI) to trace luciferase-transfected MSC. Mice were sacrificed at different time points to examine immunomodulatory changes in blood and secondary lymphoid organs. <h3>Results</h3> Both ip and local ia MSC injection resulted in a beneficial clinical and histological effect on established PGIA. BLI showed that MSC ip and ia in arthritic mice are largely retained for several weeks in the peritoneal cavity or injected joint respectively, without signs of migration. Following MSC treatment pathogenic PG-specific IgG2a antibodies in serum decreased. The Th2 cytokine IL-4 was only upregulated in PG-stimulated lymphocytes from spleens in ip treated mice and in lymphocytes from draining lymph nodes in ia treated mice. An increase in production of IL-10 was seen with equal distribution. Although IFN-γ was also elevated, the IFN-γ/IL-4 ratio in MSC treated mice was opposite to the ratio in (untreated) active PGIA. <h3>Conclusions</h3> MSC treatment, both ip and ia, suppresses PGIA, a non-collagen induced arthritis model. MSC are largely retained for weeks in the injection region. MSC treatment induced at the region of injection a deviation of PG-specific immune responses, suggesting a more regulatory phenotype with production of IL-4 and IL-10, but also of IFN-γ, and a systemic decrease of pathogenic PG-specific IgG2a antibodies. These findings underpin the potential of MSC treatment in resistant arthritis.
Evaluation of a risk assessment questionnaire to assist hepatitis C screening in the general population
Authors: F Zuure, U Davidovich, G Kok, A C Depla, C Hoebe, A van den Hoek, P L Jansen, P van Leeuwen-Gilbert, C J Weegink, R  A Coutinho, M Prins
Journal: Eurosurveillance (2010)

Many individuals with hepatitis C virus (HCV) infection are undiagnosed. This study evaluates a risk assessment questionnaire, developed for use online to target blood-screening for HCV. Two hundred and eighty-nine patients with known HCV status completed a written questionnaire on prominent HCV risk factors. Questionnaires generated advice to seek testing if at least one risk factor was reported. Agreement of the testing advice with the HCV status of respondents was evaluated. Subsequently, we validated our questionnaire among 985 patients of an outpatient clinic for sexually transmitted infections. The post-test-probability-of-disease (PTPD) and diagnostic gain (PTPD minus prior probability of disease) were calculated. The questionnaire's sensitivity and specificity were 84.6% and 63.8%, respectively, and higher in the STI clinic patients. The PTPD of positive testing advice was 72.5% given HCV prevalence of 53.0%, yielding a diagnostic gain of 19.5%. Applying the estimated prevalence in the general Dutch population (0.1-0.4%), and the anticipated prevalence in the online project (1.0-6.0%), yielded diagnostic gains of 0.13-0.53% and 1.3-7.0%, respectively. We conclude that our questionnaire succeeded in selecting at-risk individuals as its testing advice agreed well with the HCV status. We suggest that the questionnaire be used online as a selection tool for HCV blood-screening in the general population.
Dietary Glycemic Load and Cancer Recurrence and Survival in Patients with Stage III Colon Cancer: Findings From CALGB 89803
Authors: Jeffrey A. Meyerhardt, Kaori Sato, Donna Niedzwiecki, Cynthia Ye, Leonard B. Saltz, Robert J. Mayer, Rex B. Mowat, Renaud Whittom, Alexander Hantel, Al Benson, Devin S. Wigler, Alan Venook, Charles S. Fuchs
Journal: JNCI Journal of the National Cancer Institute (2012)

The influence of glycemic load and related measures on survival among colon cancer patients remains largely unknown.We conducted a prospective, observational study of 1011 stage III colon cancer patients reporting dietary intake during and 6 months after participation in an adjuvant chemotherapy trial. We examined the influence of glycemic load, glycemic index, fructose, and carbohydrate intakes on cancer recurrence and mortality using Cox proportional hazards regression; all tests of statistical significance were two-sided.Stage III colon cancer patients in the highest quintile of dietary glycemic load experienced an adjusted hazard ratio (HR) for disease-free survival of 1.79 (95% confidence interval [CI] = 1.29 to 2.48), compared with those in the lowest quintile (P (trend) across quintiles <.001). Increased glycemic load was associated with similar detriments in recurrence-free (P (trend) across quintiles <.001) and overall survival (P (trend) across quintiles <.001). These associations differed statistically significant by body mass index (BMI) (P (interaction) =.01). Whereas glycemic load was not associated with disease-free survival in patients with BMI < 25kg/m(2), higher glycemic load was statistically significant associated with worse disease-free survival among overweight or obese participants (BMI ≥ 25kg/m(2); HR = 2.26; 95% CI = 1.53 to 3.32; P (trend) across quintiles <.001). Increasing total carbohydrate intake was similarly associated with inferior disease-free, recurrence-free, and overall survival (P (trend) across quintiles <.001).Higher dietary glycemic load and total carbohydrate intake were statistically significant associated with an increased risk of recurrence and mortality in stage III colon cancer patients. These findings support the role of energy balance factors in colon cancer progression and may offer potential opportunities to improve patient survival.
Reduction in motor vehicle collisions following treatment of sleep apnoea with nasal CPAP
Authors: C F P George
Journal: Thorax (2001)

Background-Patients with untreated obstructive sleep apnoea (OSA) have increased motor vehicle collisions (MVCs).When successfully treated, they report improved driving and fewer mishaps, but there are few objective data to confirm this.A study was therefore undertaken to examine actual MVC data in a large group of patients with OSA before and after treatment with continuous positive airway pressure (CPAP) compared with a control group matched for age, sex, and type of driver's licence (commercial or noncommercial).Methods-Two hundred and ten patients of mean (SD) age 52 (11) years, body mass index (BMI) 35.5 (10) kg/m 2 , apnoea/ hypopnoea index (AHI) 54 (29) events/h were treated with CPAP for at least 3 years.MVC records were obtained from the Ontario Ministry of Transportation (MTO) database for patients and an equal number of randomly selected control drivers.MVC rates were compared for 3 years before and after CPAP therapy for patients and for the corresponding time frames for controls.Results-Untreated patients with OSA had more MVCs than controls (mean (SD) MVCs/driver/year 0.18 (0.29) v 0.06 (0.17), p<0.001).Following CPAP treatment the number of MVCs/driver/year fell to normal (0.06 (0.17)) while, in controls, the MVC rate was unchanged over time (0.06 (0.17) v 0.07 (0.18), p=NS).Thus, the change in MVCs over time between the groups was very significant (change = -0.12(95% CI -0.17 to -0.06), p<0.001)).The MVC rate in untreated patients (n=27) remained high over time.Driving exposure was not diVerent following CPAP.Conclusions-The risk of MVCs due to OSA is removed when patients are treated with CPAP.As such, any restrictions on driving because of OSA could be safely removed after treatment.
Estrogenic activity of phenolic additives determined by an in vitro yeast bioassay.
Authors: D Miller, B B Wheals, N Beresford, J P Sumpter
Journal: Environmental Health Perspectives (2001)

We used a recombinant yeast estrogen assay to assess the activity of 73 phenolic additives that are used as sunscreens, preservatives, disinfectants, antioxidants, flavorings, or for perfumery. Thirty-two of these compounds displayed activity: 22 with potencies relative to 17beta-estradiol, ranging from 1/3,000 to < 1/3,000,000, and 10 compounds with an impaired response that could not be directly compared with 17beta-estradiol. Forty-one compounds were inactive. The major criteria for activity appear to be the presence of an unhindered phenolic OH group in a para position and a molecular weight of 140-250 Da.
Laminin-Binding Integrins Induce Dll4 Expression and Notch Signaling in Endothelial Cells
Authors: Soline Estrach, Laurence Cailleteau, Claudio Areias Franco, Holger Gerhardt, Caroline Stefani, Emmanuel Lemichez, Laurent Gagnoux-Palacios, Guerrino Meneguzzi, Amel Mettouchi
Journal: Circulation Research (2011)

Integrins play a crucial role in controlling endothelial cell proliferation and migration during angiogenesis. The Delta-like 4 (Dll4)/Notch pathway establishes an adequate ratio between stalk and tip cell populations by restricting tip cell formation through "lateral inhibition" in response to a vascular endothelial growth factor gradient. Because angiogenesis requires a tight coordination of these cellular processes, we hypothesized that adhesion, vascular endothelial growth factor, and Notch signaling pathways are interconnected.This study was aimed at characterizing the cross-talk between integrin and Notch signaling in endothelial cells.Adhesion of primary human endothelial cells to laminin-111 triggers Dll4 expression, leading to subsequent Notch pathway activation. SiRNA-mediated knockdown of α2β1 and α6β1 integrins abolishes Dll4 induction, which discloses a selective integrin signaling acting upstream of Notch pathway. The increase in Foxc2 transcription, triggered by α2β1 binding to laminin, is required but not sufficient per se for Dll4 expression. Furthermore, vascular endothelial growth factor stimulates laminin γ1 deposition, which leads to integrin signaling and Dll4 induction. Interestingly, loss of integrins α2 or α6 mimics the effects of Dll4 silencing and induces excessive network branching in an in vitro sprouting angiogenesis assay on three-dimensional matrigel.We show that, in endothelial cells, ligation of α2β1 and α6β1 integrins induces the Notch pathway, and we disclose a novel role of basement membrane proteins in the processes controlling tip vs stalk cell selection.
Damage‐associated molecular pattern–activated neutrophil extracellular trap exacerbates sterile inflammatory liver injury
Authors: Hai Huang, Samer Tohme, Ahmed B. Al‐Khafaji, Sheng Tai, Patricia Loughran, Li Chen, Shu Wang, Jiyun Kim, Timothy Billiar, Yanming Wang, Allan Tsung
Journal: Hepatology (2015)

Innate immunity plays a crucial role in the response to sterile inflammation such as liver ischemia/reperfusion (I/R) injury. The initiation of liver I/R injury results in the release of damage‐associated molecular patterns, which trigger an innate immune and inflammatory cascade through pattern recognition receptors. Neutrophils are recruited to the liver after I/R and contribute to organ damage and innate immune and inflammatory responses. Formation of neutrophil extracellular traps (NETs) has been recently found in response to various stimuli. However, the role of NETs during liver I/R injury remains unknown. We show that NETs form in the sinusoids of ischemic liver lobes in vivo . This was associated with increased NET markers, serum level of myeloperoxidase–DNA complexes, and tissue level of citrullinated‐histone H3 compared to control mice. Treatment with peptidyl‐arginine‐deiminase 4 inhibitor or DNase I significantly protected hepatocytes and reduced inflammation after liver I/R as evidenced by inhibition of NET formation, indicating the pathophysiological role of NETs in liver I/R injury. In vitro, NETs increase hepatocyte death and induce Kupffer cells to release proinflammatory cytokines. Damage‐associated molecular patterns, such as High Mobility Group Box 1 and histones, released by injured hepatocytes stimulate NET formation through Toll‐like receptor (TLR4)‐ and TLR9‐MyD88 signaling pathways. After neutrophil depletion in mice, the adoptive transfer of TLR4 knockout or TLR9 knockout neutrophils confers significant protection from liver I/R injury with a significant decrease in NET formation. In addition, we found inhibition of NET formation by the peptidyl‐arginine‐deiminase 4 inhibitor and that DNase I reduces High Mobility Group Box 1 and histone‐mediated liver I/R injury. Conclusion : Damage‐associated molecular patterns released during liver I/R promote NET formation through the TLR signaling pathway. Development of NETs subsequently exacerbates organ damage and initiates inflammatory responses during liver I/R. (H epatology 2015;62:600–614