tbuckley/cabot-search huggingface dataset:
Endotoxin induces desensitization of cardiac endothelin-1 receptor signaling by increased expression of RGS4 and RGS16
Authors: M Patten
Journal: Cardiovascular Research (2002)

Objective: Endotoxin (LPS)-induced acute cardiac failure during sepsis is associated with alterations in G protein mediated signal transduction. We therefore examined the expression of the G proteins Gi, Gq, and Gs and of four 'regulators of G protein signaling' (RGS) proteins, RGS1, RGS4, RGS5, and RGS16 in rat hearts. Methods: For in vivo experiments, Wistar rats were treated with 600 μg/day E. coli LPS, intravenously) and hearts were excised after 6, 24 and 72 h. Cultured neonatal rat cardiomyocytes were treated with 4 μg/ml LPS for 24 and 72 h. Isolated membrane proteins were used for Western blot analysis and for evaluation of phospholipase C (PLC) activity. RGS16 mRNA was detected by RNAse protection. Results: LPS induced Gi protein 1.4-fold 72 h after in vivo administration of LPS, whereas expression of Gs and Gq was unaltered. After 6 h of LPS treatment, RGS16 mRNA was transiently up-regulated 3.7-fold, followed by transient protein induction (24 h: 2.5-fold; 72 h: 1.5-fold). Similarly, RGS4 protein was transiently induced (24 h: 3.1-fold; 72 h: 1.5-fold), whereas expression of RGS1 and RGS5 was not altered. Similar to the LPS-treated rat hearts, RGS16 expression was transiently induced by LPS in cultured neonatal rat cardiomyocytes (24 h: 1.6-fold, 72 h: 0.9-fold). To determine the functional consequences of the RGS protein induction phospholipase C (PLC) activity was analyzed in membranes obtained from solvent and LPS-treated hearts. Basal and endothelin-1-stimulated PLC activity was transiently repressed by LPS with a maximum after 24 h although no apparent changes in PLCβ1 or endothelin receptor expression could be detected. Conclusion: These data suggest that the rapid up-regulation of cardiac RGS4 and RGS16 is associated with a desensitization of endothelin-1 receptor signaling. Up-regulation of these RGS proteins may thus be involved in the early onset of cardiac failure during sepsis.
Thymidylate Synthase Genotype-Directed Neoadjuvant Chemoradiation for Patients With Rectal Adenocarcinoma
Authors: Benjamin R. Tan, Fabienne Thomas, Robert J. Myerson, Barbara Zehnbauer, Kathryn Trinkaus, Robert S. Malyapa, Matthew G. Mutch, Elliot E. Abbey, Amer Alyasiry, James W. Fleshman, Howard L. McLeod
Journal: Journal of Clinical Oncology (2011)

Downstaging (DS) of rectal cancers is achieved in approximately 45% of patients with neoadjuvant fluorouracil (FU) -based chemoradiotherapy (CRT). Polymorphisms in the thymidylate synthase gene (TYMS) had previously defined two risk groups associated with disparate tumor DS rates (60% v 22%). We conducted a prospective single-institution phase II study using TYMS genotyping to direct neoadjuvant CRT for patients with rectal cancer.
Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy
Authors: David A Morrow, Elliott M Antman, Milenko Tanasijevic, Nader Rifai, James A de Lemos, Carolyn H McCabe, Christopher P Cannon, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2000)
Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects
Authors: Elisa Boscolo, Nisha Limaye, Lan Huang, Kyu-Tae Kang, Julie Soblet, Melanie Uebelhoer, Antonella Mendola, Marjut Natynki, Emmanuel Seront, Sophie Dupont, Jennifer Hammer, Catherine Legrand, Carlo Brugnara, Lauri Eklund, Miikka Vikkula, Joyce Bischoff, Laurence M. Boon
Journal: Journal of Clinical Investigation (2015)

Venous malformations (VMs) are composed of ectatic veins with scarce smooth muscle cell coverage. Activating mutations in the endothelial cell tyrosine kinase receptor TIE2 are a common cause of these lesions. VMs cause deformity, pain, and local intravascular coagulopathy, and they expand with time. Targeted pharmacological therapies are not available for this condition. Here, we generated a model of VMs by injecting HUVECs expressing the most frequent VM-causing TIE2 mutation, TIE2-L914F, into immune-deficient mice. TIE2-L914F-expressing HUVECs formed VMs with ectatic blood-filled channels that enlarged over time. We tested both rapamycin and a TIE2 tyrosine kinase inhibitor (TIE2-TKI) for their effects on murine VM expansion and for their ability to inhibit mutant TIE2 signaling. Rapamycin prevented VM growth, while TIE2-TKI had no effect. In cultured TIE2-L914F-expressing HUVECs, rapamycin effectively reduced mutant TIE2-induced AKT signaling and, though TIE2-TKI did target the WT receptor, it only weakly suppressed mutant-induced AKT signaling. In a prospective clinical pilot study, we analyzed the effects of rapamycin in 6 patients with difficult-to-treat venous anomalies. Rapamycin reduced pain, bleeding, lesion size, functional and esthetic impairment, and intravascular coagulopathy. This study provides a VM model that allows evaluation of potential therapeutic strategies and demonstrates that rapamycin provides clinical improvement in patients with venous malformation.
Management Practices and the Quality of Care in Cardiac Units
Authors: K. John McConnell, Richard C. Lindrooth, Douglas R. Wholey, Thomas M. Maddox, Nick Bloom
Journal: JAMA Internal Medicine (2013)

BackgroundIn efforts to improve the quality of care, many have suggested that health care adopt management approaches that have been successful in the manufacturing and technology sectors.However, there is relatively little information about how these practices are disseminated in hospitals, and whether they are associated with better performance. MethodsWe adapted an approach used to measure management and organizational practices in manufacturing to collect management data on cardiac units, scoring performance on 18 practices, covering "Lean" methods, tracking of key performance indicators, setting targets, and incentivizing employees.Multivariate analyses assessed the relationship of management practices with process of care measures, 30-day risk adjusted mortality, and 30-day readmissions for acute myocardial infarction (AMI). ResultsWe measured management practices for 597 cardiac units, representing 51.5% of hospitals with interventional cardiac catheterization laboratories and at least 25 annual AMI discharges.We found a wide distribution in management practices, with fewer than 20% of hospitals scoring a "4" or "5" (best practice) on more than 9 measures.In multivariate analyses, management practices were significantly correlated with mortality (P=0.01) and 6 out of 6 process measures (P<0.05).No statistically significant association was found between management and 30-day readmissions. ConclusionsThe use of management practices adopted from manufacturing sectors was associated with higher process of care measures and lower 30-day AMI mortality.Given the wide differences in management practices across hospitals, dissemination of these practices may be beneficial in achieving high quality outcomes.* CI denotes confidence interval based on statistical bootstrap with hospital clustering.
Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4): a randomised, open-label, phase 3, non-inferiority study
Authors: Lawrence Blonde, Johan Jendle, Jorge Gross, Vincent Woo, Honghua Jiang, Jessie L Fahrbach, Zvonko Milicevic
Journal: The Lancet (2015)
Perspective on Kaposi's Sarcoma: Facts, Concepts, and Conjectures
Authors: M S Reitz, L S Nerurkar, R C Gallo
Journal: JNCI Journal of the National Cancer Institute (1999)

Kaposi’s sarcoma (KS) is the most common tumor associated with human immunodeficiency virus type 1 (HIV-1) infection, occurring in approximately 30% of HIV-1-infected homosexual men. The incidence of KS has increased in this risk group by more than 100 000-fold relative to the general population (1,2). However, KS is also increased in nonhomosexual HIV-infected males by about 10 000-fold (2,3). In the absence of HIV-1 infection, KS occurs very rarely in three distinct epidemiologic forms: 1) the classic form (disease seen in older men from certain ethnic groups) (4,5), 2) the endemic form (prevalent in some parts of equatorial Africa) (5,6), and 3) a form associated with renal transplant patients (7,8). It has not been clear whether all four forms of KS represent the same disease, or, like leukemias, lymphomas, and many other cancers (or immunodeficiencies), they have distinct causes and/or pathogenetic mechanisms and share only the end stage proliferation (or death) of the same cell types. A putative causative agent is human herpesvirus 8 (HHV8), also called KS-associated herpesvirus (9). HHV-8 nucleotide sequences are regularly found in all types of KS lesions (10–15), which has helped to define these tumor types as the same disorder. Aspects of KS that stimulate interest in this tumor are as follows: 1) the striking frequency of KS in HIV-1 infection, especially among homosexual men (1,16); 2) the mixed cellularity of the tumor that makes definition of the tumor cell ambiguous (17–19); 3) the question of whether the tumor is hyperplastic or neoplastic in nature (20–22); 4) the absence of KS in brain tissue; 5) the more frequent occurrence of KS in males than in females (1,2,16); 6) the relative resistance of KS to conventional therapies (which, of course, becomes worse when a patient is immunodeficient); 7) the different epidemiologic forms (noted above); 8) the absence of similar tumors in animals; and 9) the question of how HIV-1 infection dramatically increases the incidence of KS, despite the absence of HIV sequences in the KS tumor cells (18,23). (HIV-1 sequences are found only in cells infiltrating the tumor.) Until recently, there have been few reports that characterize these aspects of KS. This lack of research is due, at least in part, to the absence of a good animal model of spontaneous or induced KS and, in part, to difficulties in culturing KS tumor cells. In 1988, Gallo and colleagues (24,25) began to develop reproducible KS cell culture techniques to characterize the cultured cells (26–30), to study the role of HIV-1 in KS (31–35), to study and, when possible, to relate the in vitro cell culture data to clinical results (especially for data from KS biopsy specimens) (18), and to find biologic approaches to control tumor cell proliferation (36,37). Interpretations of the findings and hypotheses generated from this work are summarized below. KS Cell Types
The Effects of Weight Loss on Renal Function in Patients with Severe Obesity
Authors: Avry Chagnac, Tali Weinstein, Michal Herman, Judith Hirsh, Uzi Gafter, Yaacov Ori
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Severe obesity is associated with increased renal plasma flow (RPF) and glomerular filtration rate (GFR). The aim of the present study was to examine whether weight loss may reverse glomerular dysfunction in obese subjects without overt renal disease. Renal glomerular function was studied in eight subjects with severe obesity (body mass index [BMI] 48.0 ± 2.4) before and after weight loss. Nine healthy subjects served as controls. GFR and RPF were determined by measuring inulin and PAH clearance. In the obese group, GFR (145 ± 14 ml/min) and RPF (803 ± 39 ml/min) exceeded the control value by 61% (90 ± 5 ml/min, <i>P</i> = 0.001) and 32% (610 ± 41 ml/min, <i>P</i> &lt; 0.005), respectively. Consequently, filtration fraction was increased. Mean arterial pressure, although normal, was higher than in the control group (101 ± 4 <i>versus</i> 86 ± 2 mmHg, <i>P</i> &lt; 0.01). After weight loss, BMI decreased by 32 ± 4%, to 32.1 ± 1.5 (<i>P</i> = 0.001). GFR and RPF decreased to 110 ± 7 ml/min (<i>P</i> = 0.01) and 698 ± 42 ml/min (<i>P</i> &lt; 0.02), respectively. Albumin excretion rate decreased from 16 μg/min (range, 4 to 152 μg/min) to 5 μg/min (range, 3 to 37 μg/min) (<i>P</i> &lt; 0.01). Fractional clearance of albumin decreased from 3.2 × 10<sup>−6</sup> (range, 1.1 to 23 × 10<sup>−6</sup>) to 1.2 × 10<sup>−6</sup> (range, 0.5 to 6.8 × 10<sup>−6</sup>) (<i>P</i> &lt; 0.02). This study shows that obesity-related glomerular hyperfiltration ameliorates after weight loss. The improvement in hyperfiltration may prevent the development of overt obesity-related glomerulopathy. E-mail: avryc@netvision.net.il
Patients with Congenital Factor V Deficiency have Decreased Factor Xa Binding Sites on their Platelets
Authors: Joseph P. Miletich, David W. Majerus, Philip W. Majerus
Journal: Journal of Clinical Investigation (1978)

Human platelets have binding sites for plasma coagulation Factor Xa that are available only after the platelet release reaction. Platelets from 15 normal donors bound 216±52 (SD) molecules of Factor Xa per platelet. The association of Factor Xa with its platelet surface receptor results in a 300,000-fold increase in the catalytic activity of Factor Xa in forming thrombin from prothrombin. The turnover number for platelet-bound Factor Xa was 1,850±460 mol thrombin/ml per min per mol Factor Xa in experiments with platelets from 15 normal donors. Platelets from five patients with varying degrees of Factor V deficiency were investigated to determine whether or not coagulation Factor V participates in either aspect of the Factor Xa-platelet interaction. The binding of Factor Xa to platelets and the accompanying increase in rate of thrombin formation were either reduced in parallel or absent in each case with values ranging from 0 to 45% of control values. The apparent affinity of Factor Xa from Factor V-deficient patients was normal when platelet binding was detected. The supernate from thrombin-treated control platelets, which contains Factor V activity, corrected the Factor Xa binding deficiency of the platelets from three patients tested. Immunoreactive Factor V determined with an homologous antibody corresponded to the functional Factor V activity of platelets from one patient with Factor V deficiency, suggesting that the patient's platelets have a decreased amount of normal Factor V.
Predictive network modeling of the high-resolution dynamic plant transcriptome in response to nitrate
Authors: Gabriel Krouk, Piotr Mirowski, Yann LeCun, Dennis E Shasha, Gloria M Coruzzi
Journal: Genome biology (2010)

Abstract Background Nitrate, acting as both a nitrogen source and a signaling molecule, controls many aspects of plant development. However, gene networks involved in plant adaptation to fluctuating nitrate environments have not yet been identified. Results Here we use time-series transcriptome data to decipher gene relationships and consequently to build core regulatory networks involved in Arabidopsis root adaptation to nitrate provision. The experimental approach has been to monitor genome-wide responses to nitrate at 3, 6, 9, 12, 15 and 20 minutes using Affymetrix ATH1 gene chips. This high-resolution time course analysis demonstrated that the previously known primary nitrate response is actually preceded by a very fast gene expression modulation, involving genes and functions needed to prepare plants to use or reduce nitrate. A state-space model inferred from this microarray time-series data successfully predicts gene behavior in unlearnt conditions. Conclusions The experiments and methods allow us to propose a temporal working model for nitrate-driven gene networks. This network model is tested both in silico and experimentally. For example, the over-expression of a predicted gene hub encoding a transcription factor induced early in the cascade indeed leads to the modification of the kinetic nitrate response of sentinel genes such as NIR , NIA2 , and NRT1.1 , and several other transcription factors. The potential nitrate/hormone connections implicated by this time-series data are also evaluated.
A prospective, randomized trial comparing lymphoblastoid to recombinant interferon alfa 2a as therapy for chronic hepatitis C
Authors: M Rumi, E Del Ninno, M L Parravicini, R Romeo, R Soffredini, M F Donato, J Wilber, A Russo, M Colombo
Journal: Hepatology (1996)

To compare the long-term effectiveness and tolerability of lymphoblastoid interferon (IFN-αN1) and recombinant interferon alfa 2a (IFN-α2a) in patients with chronic hepatitis caused by hepatitis C virus (HCV), 234 consecutive patients with HCV-related chronic hepatitis were randomized prospectively to receive titrated doses (starting dose = 6 million units [MU]) of IFN-α2a (n = 118) or IFN-αN1 (n = 116) for 12 months. HCV RNA was detected by reverse- transcription polymerase chain reaction (RT-PCR), quantified by branched-DNA (bDNA) assay, and genotyped by reverse hybridization assay. Thirty-one patients in the IFN-α2a group and 28 in the IFN- αN1 group (total, 59 [25%]) had normal transaminases and undetectable HCV RNA by RT-PCR after 12 months of therapy, but only 19 in the first group and 20 in the second group (total, 39 [17%]) had biochemical and virological responses 12 months after treatment was discontinued. The two treatment groups differed in terms of prevalence of major drug-related adverse reactions (23% vs. 37%, P = .025). The mean total dose per patient was similar for the two groups, i.e., 502 MU IFN-α2a vs. 496 MU IFN-αN1, and the cost of each sustained response was $31,800 and $32,440, respectively. By multivariate analysis, pretreatment viremia higher than 0.2 MEq/mL and infection with genotype 1 were independently associated to treatment failure. The outcome of treatment in chronic hepatitis C patients was not improved by the administration of high cumulative doses of lymphoblastoid IFN.
Incidence, characteristics and outcomes of patients with severe community acquired-MRSA pneumonia
Authors: K. Z. Vardakas, D. K. Matthaiou, M. E. Falagas
Journal: European Respiratory Journal (2009)

We evaluated the published data for the incidence, characteristics and outcomes of patients with community-acquired pneumonia (CAP) due to methicillin-resistant Staphylococcus aureus (MRSA). The estimated incidence of MRSA CAP is 0.51–0.64 cases per 100,000. We identified 74 articles reporting data on 114 patients. Influenza like symptoms was reported in 41% of patients. Pneumonia improved in 59 (54.1%) out of 109 patients; 49 (44.5%) out of 110 patients died. The duration of hospitalisation was 38.1±24.9 and 8.3±11.7 days, respectively. The duration of intensive care unit (ICU) stay was 18.9±13.6 and 6.8±9.7 days, respectively. 76 strains carried the Panton–Valentine leukocidin gene. The univariate analysis showed that multi-organ failure (p&lt;0.001), leukopenia (p&lt;0.001), admission to ICU (p&lt;0.001), mechanical ventilation (p&lt;0.001), use of aminoglycosides after culture results (p&lt;0.001), shock (p = 0.001), acute respiratory distress syndrome (p = 0.001), influenza like symptoms (p = 0.008), disseminated intravascular coagulation (p = 0.042) and rash (p = 0.04) were the factors associated with death.
New Jejunostomy Feed
Authors: J. T. Hindmarsh, R. G. Clark
Journal: BMJ (1973)

Three patients with duodenal fistulae were fed solely with an easily prepared, inexpensive jejunostomy feed for 14, 21, and 23 days respectively. Sodium, potassium, and nitrogen balances became positive, diarrhoea did not develop, and body weight increased. The feed was life-saving: the patients9 superficial veins were thrombosed, and percaval feeding was considered undesirable.
Familial pneumothoraces and bullae.
Authors: G J Gibson
Journal: Thorax (1977)

The cases of three sisters who presented with spontaneous pneumothoraces are described. In two of the patients large bullae were clearly demonstrable. No recognisable associations of bullae or pneumothorax were present and there was no evidence of generalised emphysema. The cases suggest a familial predisposition to the development of bullae in otherwise apparently healthy lungs.
Human Tumor Cells Killed by Anthracyclines Induce a Tumor-Specific Immune Response
Authors: Jitka Fucikova, Petra Kralikova, Anna Fialova, Tomas Brtnicky, Lukas Rob, Jirina Bartunkova, Radek Špíšek
Journal: Cancer Research (2011)

Immunogenic cell death is characterized by the early surface exposure of chaperones including calreticulin and HSPs, which affect dendritic cell (DC) maturation and the uptake and presentation of tumor antigens. It has also been shown that it is characterized by the late release of high mobility group box 1 (HMGB1), which acts through Toll-like receptor 4 (TLR4) and augments the presentation of antigens from dying tumor cells to DCs. Most of the data on immunogenic tumor cell death were obtained using mouse models. In this study, we investigated the capacity of clinically used chemotherapeutics to induce immunogenic cell death in human tumor cell lines and primary tumor cells. We found that only anthracyclines induced a rapid translocation of calreticulin, HSP70, and HSP90 to the cell surface and the release of HMGB1 12 hours after the treatment. The interaction of immature DCs with immunogenic tumor cells led to an increased tumor cell uptake and induces moderate phenotypic maturation of DCs. Killed tumor cell-loaded DCs efficiently stimulated tumor-specific IFN-γ-producing T cells. DCs pulsed with killed immunogenic tumor cells also induced significantly lower numbers of regulatory T cells than those pulsed with nonimmunogenic tumor cells. These data indicate that human prostate cancer, ovarian cancer, and acute lymphoblastic leukemia cells share the key features of immunogenic cell death with mice tumor cells. These data also identify anthracyclines as anticancer drugs capable of inducing immunogenic cell death in sensitive human tumor cells.
295 HUMAN INDUCED PLURIPOTENT STEM CELLS (iPSCs) REPROGRAMMED WITH HOME-MADE-mRNAs: A TOOL FOR STEM-CELL DERIVED HEPATOCYTE STUDIES
Authors: C. Steichen, E. Luce, S. Goulinet-Mainot, L. Tosca, G. Tachdjian, D. Burks, A. Weber, J. Marie, A. Dubart-Kupperschmitt
Journal: Journal of Hepatology (2013)
Effects of Decreased Respiratory Frequency on Ventilator-induced Lung Injury
Authors: JOHN R. HOTCHKISS, LLUIS BLANCH, GASTON MURIAS, ALEXANDER B. ADAMS, DOUG A. OLSON, O. D. WANGENSTEEN, PERRY H. LEO, JOHN J. MARINI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

To determine if decreased respiratory frequency (ventilatory rate) improves indices of lung damage, 17 sets of isolated, perfused rabbit lungs were ventilated with a peak static airway pressure of 30 cm H(2)O. All lungs were randomized to one of three frequency/peak pulmonary artery pressure combinations: F20P35 (n = 6): ventilatory frequency, 20 breaths/min, and peak pulmonary artery pressure, 35 mm Hg; F3P35 (n = 6), ventilatory frequency, 3 breaths/min, and peak pulmonary artery pressure of 35 mm Hg; or F20P20 (n = 5), ventilatory frequency, 20 breaths/min, and peak pulmonary artery pressure, 20 mm Hg. Mean airway pressure and tidal volume were matched between groups. Mean pulmonary artery pressure and vascular flow were matched between groups F20P35 and F3P35. The F20P35 group showed at least a 4.5-fold greater mean weight gain and a 3-fold greater mean incidence of perivascular hemorrhage than did the comparison groups, all p </= 0.05. F20P35 lungs also displayed more alveolar hemorrhage than did F20P20 lungs (p </= 0.05). We conclude that decreasing respiratory frequency can improve these indices of lung damage, and that limitation of peak pulmonary artery pressure and flow may diminish lung damage for a given ventilatory pattern.
What Is the Role of Serologic Testing in Celiac Disease? A Prospective, Biopsy-Confirmed Study With Economic Analysis
Authors: Andrew D. Hopper, Marios Hadjivassiliou, David P. Hurlstone, Alan J. Lobo, Mark E. McAlindon, William Egner, Graeme Wild, David S. Sanders
Journal: Clinical Gastroenterology and Hepatology (2008)
Aberrant glycosylation of IgA in Wiskott-Aldrich syndrome and X-linked thrombocytopenia
Authors: Masaki Shimizu, Hirokazu Kanegane, Taizo Wada, Yaeko Motoyoshi, Tomohiro Morio, Fabio Candotti, Akihiro Yachie
Journal: Journal of Allergy and Clinical Immunology (2012)