tbuckley/cabot-search huggingface dataset:
RhoA Activation by Hypoxia in Pulmonary Arterial Smooth Muscle Cells Is Age and Site Specific
Authors: Karine Bailly, Anne J. Ridley, Susan M. Hall, Sheila G. Haworth
Journal: Circulation Research (2004)

Hypoxia induces vasoconstriction of pulmonary arteries through contraction of smooth muscle cells (SMCs). The GTPase RhoA regulates smooth muscle contractility and actin cytoskeletal remodeling through the Rho-associated kinase (ROCK). We previously found that the postnatal fall in pulmonary vascular resistance was associated with actin cytoskeletal remodeling in porcine pulmonary arterial SMCs (PASMCs) in vivo. Here, we investigated the effects of acute and chronic hypoxia on the morphology and RhoA activity of PASMCs from fetal and neonatal piglets. Acute hypoxia enhanced actin stress fiber formation and RhoA activity in both inner and outer medial PASMCs from the fetus but only in the inner medial PASMCs from normal 3-day-old piglets. The increased stress fiber formation was dependent on Rho and ROCK. In outer medial PASMCs from 14-day-old animals, acute hypoxia decreased RhoA activity. Interestingly, outer medial PASMCs from animals exposed to chronic hypoxia had fewer stress fibers associated with a lower basal RhoA activity. Treatment of PASMCs from normal 3-day-old piglets with Rho or ROCK inhibitors for 24 hours induced a similar morphology. Rac activity was not altered by either acute or chronic hypoxia. These data show that acute hypoxia induces RhoA activation only in PASMCs from young animals, whereas chronic hypoxia selectively downregulates RhoA activity in outer medial PASMCs leading to an altered phenotype.
Human Embryonic and Induced Pluripotent Stem Cell–Derived Cardiomyocytes Exhibit Beat Rate Variability and Power-Law Behavior
Authors: Yael Mandel, Amir Weissman, Revital Schick, Lili Barad, Atara Novak, Gideon Meiry, Stanislav Goldberg, Avraham Lorber, Michael R. Rosen, Joseph Itskovitz-Eldor, Ofer Binah
Journal: Circulation (2012)

Background— The sinoatrial node is the main impulse-generating tissue in the heart. Atrioventricular conduction block and arrhythmias caused by sinoatrial node dysfunction are clinically important and generally treated with electronic pacemakers. Although an excellent solution, electronic pacemakers incorporate limitations that have stimulated research on biological pacing. To assess the suitability of potential biological pacemakers, we tested the hypothesis that the spontaneous electric activity of human embryonic stem cell–derived cardiomyocytes (hESC-CMs) and induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) exhibit beat rate variability and power-law behavior comparable to those of human sinoatrial node. Methods and Results— We recorded extracellular electrograms from hESC-CMs and iPSC-CMs under stable conditions for up to 15 days. The beat rate time series of the spontaneous activity were examined in terms of their power spectral density and additional methods derived from nonlinear dynamics. The major findings were that the mean beat rate of hESC-CMs and iPSC-CMs was stable throughout the 15-day follow-up period and was similar in both cell types, that hESC-CMs and iPSC-CMs exhibited intrinsic beat rate variability and fractal behavior, and that isoproterenol increased and carbamylcholine decreased the beating rate in both hESC-CMs and iPSC-CMs. Conclusions— This is the first study demonstrating that hESC-CMs and iPSC-CMs exhibit beat rate variability and power-law behavior as in humans, thus supporting the potential capability of these cell sources to serve as biological pacemakers. Our ability to generate sinoatrial-compatible spontaneous cardiomyocytes from the patient's own hair (via keratinocyte-derived iPSCs), thus eliminating the critical need for immunosuppression, renders these myocytes an attractive cell source as biological pacemakers.
Association of duration of television viewing in early childhood with the subsequent development of asthma
Authors: A Sherriff, A Maitra, A R Ness, C Mattocks, C Riddoch, J J Reilly, J Y Paton, A J Henderson
Journal: Thorax (2009)

Objective: To investigate whether duration of television (TV) viewing in young children is associated with subsequent development of asthma. Methods: Children taking part in the Avon Longitudinal Study of Parents and Children (ALSPAC) with no wheeze up to the age of 3.5 years and follow-up data at 11.5 years of age took part in a prospective longitudinal cohort study. The main outcome measure was asthma, defined as doctor-diagnosed asthma by 7.5 years of age with symptoms and/or treatment in the previous 12 months at 11.5 years of age. Parental report of hours of TV viewing per day by the children was ascertained at 39 months. Results: In children with no symptoms of wheeze at 3.5 years of age and follow-up data at 11.5 years of age, the prevalence of asthma was 6% (185/3065). Increased TV viewing at 3.5 years was associated with increased prevalence of asthma at 11.5 years of age (p for linear trend = 0.0003). Children who watched television for >2 h/day were almost twice as likely to develop asthma by 11.5 years of age as those watching TV for 1–2 h/day (adjusted odds ratio 1.8 (95% CI 1.2 to 2.6)). Conclusion: Longer duration of TV viewing in children with no symptoms of wheeze at 3.5 years of age was associated with the development of asthma in later childhood.
The Multikinase Inhibitor Sorafenib Potentiates TRAIL Lethality in Human Leukemia Cells in Association with Mcl-1 and cFLIPL Down-regulation
Authors: Roberto R. Rosato, Jorge A. Almenara, Stefanie Coe, Steven Grant
Journal: Cancer Research (2007)

Abstract Interactions between the multikinase inhibitor sorafenib and tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) were examined in malignant hematopoietic cells. Pretreatment (24 h) of U937 leukemia cells with 7.5 μmol/L sorafenib dramatically increased apoptosis induced by sublethal concentrations of TRAIL/Apo2L (75 ng/mL). Similar interactions were observed in Raji, Jurkat, Karpas, K562, U266 cells, primary acute myelogenous leukemia blasts, but not in normal CD34+ bone marrow cells. Sorafenib/TRAIL–induced cell death was accompanied by mitochondrial injury and release of cytochrome c, Smac, and AIF into the cytosol and caspase-9, caspase-3, caspase-7, and caspase-8 activation. Sorafenib pretreatment down-regulated Bcl-xL and abrogated Mcl-1 expression, whereas addition of TRAIL sharply increased Bid activation, conformational change of Bak (ccBak) and Bax (ccBax), and Bax translocation. Ectopic Mcl-1 expression significantly attenuated sorafenib/TRAIL–mediated lethality and dramatically reduced ccBak while minimally affecting levels of ccBax. Similarly, inhibition of the receptor-mediated apoptotic cascade with a caspase-8 dominant-negative mutant significantly blocked sorafenib/TRAIL–induced lethality but not Mcl-1 down-regulation or Bak/Bax conformational change, indicating that TRAIL-mediated receptor pathway activation is required for maximal lethality. Sorafenib/TRAIL did not increase expression of DR4/DR5, or recruitment of procaspase-8 or FADD to the death-inducing signaling complex (DISC), but strikingly increased DISC-associated procaspase-8 activation. Sorafenib also down-regulated cFLIPL, most likely through a translational mechanism, in association with diminished eIF4E phosphorylation, whereas ectopic expression of cFLIPL significantly reduced sorafenib/TRAIL lethality. Together, these results suggest that in human leukemia cells, sorafenib potentiates TRAIL-induced lethality by down-regulating Mcl-1 and cFLIPL, events that cooperate to engage the intrinsic and extrinsic apoptotic cascades, culminating in pronounced mitochondrial injury and apoptosis. [Cancer Res 2007;67(19):9490–500]
Risk factors and clinical relevance of nosocomial maxillary sinusitis in the critically ill.
Authors: J J Rouby, P Laurent, M Gosnach, E Cambau, G Lamas, A Zouaoui, J L Leguillou, L Bodin, T D Khac, C Marsault
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The incidence of infectious maxillary sinusitis (IMS) and its clinical relevance was prospectively studied in 162 consecutive critically ill patients who were mechanically ventilated for a period longer than 7 d. All had a paranasal computed tomographic (CT) scan within 48 h of admission and were divided into three groups according to the radiologic aspect of their maxillary sinuses: Group 1 = normal maxillary sinuses (n = 40), Group 2 = maxillary mucosal thickening (n = 26), Group 3 = radiologic maxillary sinusitis (RMS) defined as the presence of an air fluid level and/or opacification of maxillary sinuses (n = 96). Group 1 patients were randomized between nasal and oral endotracheal intubation with a gastric intubation performed via the same route and had a second paranasal CT scan 7 d later. Endotracheal and gastric tubes were left in their original position in Group 2 patients and a second paranasal CT scan was performed 7 d later. All patients of Group 3 underwent a transnasal puncture for bacteriologic analysis of maxillary sinus content. Forty-five spontaneously breathing patients served as a control group. In all patients with RMS, the occurrence of bronchopneumonia (BPN) was prospectively assessed for 7 d following the initial CT scan. Upon inclusion, only 25% of the patients had normal maxillary sinuses whereas all patients in the control group had normal paranasal CT scans. After 7 d, 46% of Group 2 patients had evidence of RMS. Risk factors for RMS were nasal placement and duration of endotracheal and gastric intubation.(ABSTRACT TRUNCATED AT 250 WORDS)
Overexpressed proprotein convertase 1/3 induces an epithelial-mesenchymal transition in airway epithelium
Authors: Sang-Nam Lee, Da-Hyung Lee, Myung Hyun Sohn, Joo-Heon Yoon
Journal: European Respiratory Journal (2013)

The proprotein convertases (PCs) are serine proteases responsible for the proteolytic maturation of many precursor proteins involved in upper airway remodelling during nasal polyposis. We have previously found that PC1/3 is expressed in human nasal mucosa. However, whether PC1/3 is related to nasal polyp formation has not been investigated. To gain insight into the functional role of PC1/3 in nasal polyps, we determined PC1/3 expression in nasal polyps by immunostaining, Western blotting and enzyme assays and generated stable cells expressing PC1/3 using airway epithelial cell line NCI-H292. Nasal polyps exhibit increased PC1/3 expression compared to normal nasal mucosa. PC1/3 was expressed in neuroendocrine cells in normal nasal mucosa and it was also expressed in goblet and ciliated cells in nasal polyps. NCI-H292 cells stably expressing PC1/3 displayed morphological changes, enhanced cell proliferation and migration, downregulation of E-cadherin and cytokeratins and upregulation of N-cadherin, vimentin, matrix metalloproteinase-2, collagen-I, snail and twist. Importantly, PC1/3 expression was positively correlated with epithelial-mesenchymal transition in cultured human nasal epithelial cells and in nasal polyps. Taken together, our data suggest that PC1/3 overexpression induces morphological and phenotypic epithelial-mesenchymal transition changes of airway epithelial cells and these changes may contribute to the pathogenesis of nasal polyps.
(32) Tattoo reaction with generalized lichen planus
Authors: V.S. Neild, E.L. Rhodes
Journal: British Journal of Dermatology (1985)

Journal Article (32) Tattoo reaction with generalized lichen planus Get access V.S. Neild, V.S. Neild St Helier Hospital, Carshalton Search for other works by this author on: Oxford Academic Google Scholar E.L. Rhodes E.L. Rhodes St Helier Hospital, Carshalton Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s29, 1 July 1985, Page 77, https://doi.org/10.1111/j.1365-2133.1985.tb13047.x Published: 01 July 1985
Generation of oxygen free radicals from blood eosinophils from asthma patients after stimulation with PAF or phorbol ester
Authors: P Chanez, G Dent, T Yukawa, PJ Barnes, KF Chung
Journal: European Respiratory Journal (1990)

Eosinophils (EOS) may play an important role in the pathophysiology of bronchial asthma because they can release oxygen free radicals and several basic proteins which are cytotoxic to bronchial epithelium. We have studied the response of EOS isolated from the blood of atopic subjects with symptoms of asthma (AS, n = 7) or rhinitis (AR, n = 4) or without symptoms (AA, n = 5) and of subjects with the hypereosinophilic syndrome (HES, n = 5). EOS were separated using metrizamide density gradients and activated in vitro with platelet-activating factor (PAF, 100 nM) or phorbol 12-myristate-13-acetate (PMA, 100 nM). Oxygen free radical generation was assessed by a lucigenin-enhanced chemiluminescence (CL) assay. EOS purity was 83 +/- 1.7% (mean +/- SEM) with greater than 95% viability. Background CL responses of EOS from HES were significantly higher than those from AA (p less than 0.01) and AR (p less than 0.05). Normodense EOS from AS (PAF-induced CL = 90 +/- 27 mV) were more responsive to PAF than were those from AR (17 +/- 13 mV, p less than 0.01) and from AA (23 +/- 14 mV, p less than 0.01). Similar results were obtained with PMA. Hypodense EOS from HES subjects were as responsive as normodense EOS from AS to PMA and PFA. Thus, EOS from AS have an enhanced potential for activation, particularly by PAF; this may represent an important mechanism for the perpetuation of the inflammatory response in asthma, since EOS can also release PAF.
Effect of Treatment With Zileuton, a 5-Lipoxygenase Inhibitor, in Patients With Asthma
Authors: Elliot Israel
Journal: JAMA (1996)

To study the effect of 3 months of treatment with zileuton, an inhibitor of the enzymatic pathway (5-lipoxygenase) leading to leukotriene formation, on disease control in patients with mild to moderate asthma.Randomized, double-blind, parallel-group study in 401 patients. A 10-day placebo lead-in was followed by a double-blind treatment period of 13 weeks.Asthma study clinics in university hospitals and private practices.Patients with mild to moderate asthma (forced expiratory volume in the first second [FEV1], 40% to 80% of predicted) whose only treatment was inhaled beta-agonists.Treatment with 600 mg or 400 mg of zileuton or placebo (each taken four times daily.)Frequency of asthma exacerbation requiring treatment with corticosteroids, use of inhaled beta-agonists, pulmonary function tests, asthma symptom assessment, and quality-of-life evaluation. Safety was evaluated by monitoring adverse events.Only eight (6.1%) of 132 patients receiving 600 mg of zileuton four times a day required corticosteroid treatment for asthma vs 21 (15.6%) of 135 patients receiving placebo (P=.02), giving a relative risk of 2.6. At the time of expected peak drug concentration, the average FEV1 improved 15.7% in the 600-mg zileuton group vs 7.7% in the placebo group (P=.006). Quality-of-life assessments significantly improved in the 600-mg zileuton group and not in the placebo group (P=.007 for the overall score). Elevations in liver function tests (more than three times normal), all of which reversed with drug withdrawal, occurred in five patients (P=.03 vs placebo), three patients (P=.12 vs placebo), and no patients treated with 600 mg of zileuton, 400 mg of zileuton, or placebo, respectively.Three months of 5-lipoxygenase inhibition produced a significant improvement in asthma control. These data indicate that 5-lipoxygenase products of arachidonic acid metabolism are mediators of inflammation with an important role in the biology of asthma.
IMMUNOSORBENT ASSAYS FOR DIAGNOSIS OF HAEMORRHAGIC FEVER WITH RENAL SYNDROME
Authors: M.A Donets, G.V Rezapkin, E.V Leshchinskaya, U.M Zagidulin, A.A Ivanova, O.V Stradukhin, N.M Mustafin, T.I Savinova, E.A Tkachenko, A.P Ivanov, T.K Dzagurova
Journal: The Lancet (1981)
COX-2–Independent Effects of Celecoxib Sensitize Lymphoma B Cells to TRAIL-Mediated Apoptosis
Authors: Anne-Sophie Gallouet, Marion Travert, Laurence Bresson-Bepoldin, Fabien Guilloton, Céline Pangault, Sylvie Caulet-Maugendre, Thierry Lamy, Karin Tarte, Thierry Guillaudeux
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Despite therapeutic advances, non–Hodgkin lymphomas (NHL) remain incurable. They form a group of neoplasms strongly dependent on their inflammatory microenvironment, which plays an important supportive role in tumor B-cell survival and in the resistance to antitumor immune response. New therapies must consider both tumor cells and their surrounding microenvironment Experimental Design: Stromal cells, derived from bone marrow or lymph nodes, and B cells from follicular lymphoma patients were cocultured or cultured alone with celecoxib treatment, a nonsteroidal anti-inflammatory drug, and/or TRAIL, a promising cytotoxic molecule for cancer therapy. Results: In this study, we show that follicular lymphoma stromal cells produce large amounts of PGE2. This production is abrogated after celecoxib treatment, targeting the COX-2 isoenzyme involved in PGE2 synthesis. Furthermore, we demonstrate that celecoxib increases apoptosis in NHL B-cell lines and in primary follicular lymphoma B cells cocultured with stromal cells, but independently of the PGE2/COX-2 axis. Finally, celecoxib increases the apoptotic activity of TRAIL. We provide evidence that celecoxib affects proliferation and sensitizes NHL B-cell lines to apoptosis through COX-2–independent effects by slowing down the cell cycle and decreasing the expression of survival proteins, such as Mcl-1. Conclusions: These data suggest new potent strategies for NHL therapy combining drugs targeting both tumor B cells and survival signals provided by the tumor microenvironment. Clin Cancer Res; 20(10); 2663–73. ©2014 AACR.
Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222
Authors: Joseph O. Moore, Stephen L. George, Richard K. Dodge, Philip C. Amrein, Bayard L. Powell, Jonathan E. Kolitz, Maria R. Baer, Frederick R. Davey, Clara D. Bloomfield, Richard A. Larson, Charles A. Schiffer
Journal: Blood (2004)
Increased intrahepatic cyclooxygenase 2, matrix metalloproteinase 2, and matrix metalloproteinase 9 expression is associated with progressive liver disease in chronic hepatitis C virus infection: role of viral core and NS5A proteins
Authors: O Nunez
Journal: Gut (2004)

<b>Background:</b> Cyclooxygenase 2 (COX-2) and matrix metalloproteinases (MMPs) have been implicated in tissue injury and fibrogenesis in animal models but little is known regarding their role in hepatitis C virus (HCV) related liver disease in humans. <b>Aims:</b> To characterise the intrahepatic expression pattern of COX-2 and MMPs in chronic HCV infection and determine whether HCV core and NS5A proteins could promote their expression in cultured hepatocyte derived cell lines. <b>Patients:</b> Thirty two anti-HCV+ and 10 anti-HCV− patients were studied. <b>Methods:</b> Western blot, reverse transcription-polymerase chain reaction (RT-PCR), enzyme immunoassay, and immunohistochemistry were used to assess the expression pattern of COX-2 and MMPs in liver biopsy samples from all patients. COX-2 gene expression and MMP-9 protein levels were also determined by immunoblot, RT-PCR, and luciferase assays in core and NS5A transfected hepatocyte derived cells. <b>Results:</b> The intrahepatic expression level of COX-2, MMP-2, and MMP-9 was significantly higher in HCV+ than in HCV− patients, increasing with the fibrotic stage of liver disease. We further demonstrated that COX-2 mRNA, protein, and activity were induced in resting and activated core and NS5A transfectants. Both viral proteins induced transcriptional activity of the COX-2 gene promoter whereas core, but not NS5A, exerted an inducer effect on MMP-9 protein levels in cultured hepatocyte derived cells. <b>Conclusions:</b> Intrahepatic COX-2, MMP-2, and MMP-9 overexpression is associated with progressive hepatic fibrosis in chronic HCV infection, suggesting their pathogenic role in fibrogenesis. HCV core and NS5A proteins were able to upregulate COX-2 and MMP-9 gene expression in hepatocyte derived cells, providing a potential mechanism for hepatic fibrosis during chronic HCV infection.
Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor
Authors: Onisha Patel, Daniel G Pellicci, Stephanie Gras, Maria L Sandoval-Romero, Adam P Uldrich, Thierry Mallevaey, Andrew J Clarke, Jérôme Le Nours, Alex Theodossis, Susanna L Cardell, Laurent Gapin, Dale I Godfrey, Jamie Rossjohn
Journal: Nature Immunology (2012)
Are Outcomes of Surgical Versus Transcatheter Balloon Valvotomy Equivalent in Neonatal Critical Aortic Stenosis?
Authors: Brian W. McCrindle, Eugene H. Blackstone, William G. Williams, Rekwan Sittiwangkul, Thomas L. Spray, Anthony Azakie, Richard A. Jonas
Journal: Circulation (2001)

For neonates with critical aortic valve stenosis who are selected for biventricular repair, valvotomy can be achieved surgically (SAV) or by transcatheter balloon dilation (BAV).Data regarding 110 neonates with critical aortic valve stenosis were evaluated in a study by the Congenital Heart Surgeons Society from 1994 to 1999. Reduced left ventricular function was present in 46% of neonates. The initial procedure was SAV in 28 patients and BAV in 82 patients. Mean percent reduction in systolic gradient was significantly greater with BAV (65+/-17%) than SAV (41+/-32%; P<0.001). Higher residual median gradients were present in the SAV versus BAV group (36 mm Hg [range, 10 to 85 mm Hg] versus 20 mm Hg [0 to 85 mm Hg], P<0.001). Important aortic regurgitation was more often present after BAV (18%) than SAV (3%; P=0.07). Time-related survival after valvotomy was 82% at 1 month and 72% at 5 years, with no significant difference for SAV versus BAV, even after adjustment for differences in patient and disease characteristics. Independent risk factors for mortality were mechanical ventilation before valvotomy, smaller aortic valve annulus (z score), smaller aortic diameter at the sinotubular junction (z score), and a smaller subaortic region. A second procedure was performed in 46 survivors. Estimates for freedom from reintervention were 91% at 1 month and 48% at 5 years after the initial valvotomy and did not differ significantly between groups.SAV and BAV for neonatal critical aortic stenosis have similar outcomes. There is a greater likelihood of important aortic regurgitation with BAV and of residual stenosis with SAV.