tbuckley/cabot-search huggingface dataset:
Regulation of nuclear factor kappaB by corticosteroids in rat mesangial cells.
Authors: R B Auwardt, S J Mudge, C G Chen, D A Power
Journal: Journal of the American Society of Nephrology (1998)

Nuclear factor kappaB (NF-kappaB) is one of the most important proinflammatory transcription factors. The anti-inflammatory activity of steroids in leukocytes is partly due to inhibition of signaling by NF-kappaB, but it is not known whether steroids inhibit NF-kappaB in kidney cells. Since the mesangial cell is important in several kidney diseases, especially mesangial proliferative glomerulonephritis, the aims of this study were: (1) to define the mechanism of NF-kappaB activation in rat glomerular mesangial cells; and (2) to determine whether steroids inhibit activation of NF-kappaB in these cells. Electrophoretic mobility shift assays (EMSA) showed that interleukin-1beta and tumor necrosis factor-alpha activated NF-kappaB from 15 min to 48 h after stimulation. Supershift EMSA demonstrated that p65 and p50 were the predominant subunits involved. Degradation of the inhibitory subunit IkappaB-alpha was first observed 15 min after stimulation by Western blot, was maximal at 15 to 30 min (>90% by densitometry), and had returned to near normal levels at 90 min. In contrast, IkappaB-beta was maximally degraded at 60 to 120 min and was still reduced at 48 h (<50% of the untreated level). Although treatment of mesangial cells with dexamethasone increased IkappaB-alpha mRNA by 1.92x and protein by 1.45x over controls, pretreatment did not inhibit degradation of IkappaB-alpha or -beta in response to stimulation, or prevent the increase in NF-kappaB binding activity shown by EMSA. However, dexamethasone significantly inhibited the increase in monocyte chemoattractant protein-1 mRNA seen after stimulation with interleukin 1beta, although this was not complete. It did not reduce transcription of an NF-kappaB reporter. In comparison, the pyrrolidine derivative of dithiocarnamate (PDTC), a known inhibitor of NF-kappaB, prevented the increase in NF-kappaB binding activity and significantly reduced transcription of the NF-kappaB reporter. These studies suggest that steroids can partially inhibit transcriptional activation by NF-kappaB in mesangial cells but not through an increase in IkappaB-alpha protein alone. Their effect must occur at the promoter and may be restricted to some NF-kappaB-responsive genes. Therapies that block NF-kappaB more effectively than steroids in mesangial cells, therefore, may be useful in the treatment of mesangial proliferative glomerulonephritis.
Basophil Hyporesponsiveness Following Six Months of Peanut Oral Immunotherapy (OIT) Is Associated with Suppression of Syk Phosphorylation
Authors: Michael D. Kulis, Caitlin Burk, Xiaohong Yue, Huamei Zhang, Pamela H. Steele, Deanna K. Hamilton, Ayeshia Beavers, Benjamin L. Wright, Soman N. Abraham, Brian P. Vickery, A. Wesley Burks
Journal: Journal of Allergy and Clinical Immunology (2015)
Characterization of Left Ventricular Activation in Patients With Heart Failure and Left Bundle-Branch Block
Authors: Angelo Auricchio, Cecilia Fantoni, Francois Regoli, Corrado Carbucicchio, Andreas Goette, Christoph Geller, Michael Kloss, Helmut Klein
Journal: Circulation (2004)

Conventional activation mapping in the dilated human left ventricle (LV) with left bundle-branch block (LBBB) morphology is incomplete given the limited number of recording sites that may be collected in a reasonable time and given the lack of precision in marking specific anatomic locations.We studied LV activation sequences in 24 patients with heart failure and LBBB QRS morphology with simultaneous application of 3D contact and noncontact mapping during intrinsic rhythm and asynchronous pacing. Approximately one third of the patients with typical LBBB QRS morphology had normal transseptal activation time and a slightly prolonged or near-normal LV endocardial activation time. A "U-shaped" activation wave front was present in 23 patients because of a line of block that was located anteriorly (n=12), laterally (n=8), and inferiorly (n=3). Patients with a lateral line of block had significantly shorter QRS (P<0.003) and transseptal durations (P<0.001) and a longer distance from the LV breakthrough site to line of block (P<0.03). Functional behavior of the line of block was demonstrated by a change in its location during asynchronous ventricular pacing at different sites and cycle lengths.A U-shaped conduction pattern is imposed on the LV activation sequence by a transmural functional line of block located between the LV septum and the lateral wall with a prolonged activation time. Assessment of functional block is facilitated by noncontact mapping, which may be useful for identifying and targeting specific locations that are optimal for successful cardiac resynchronization therapy.
Development of intraepithelial T lymphocytes in the intestine of irradiated SCID mice by adult liver hematopoietic stem cells from normal mice
Authors: Satoshi Yamagiwa, Shuhji Seki, Katsuaki Shirai, Yuhei Yoshida, Chikako Miyaji, Hisami Watanabe, Toru Abo
Journal: Journal of Hepatology (1999)
Self-Renewal of Multipotent Long-Term Repopulating Hematopoietic Stem Cells Is Negatively Regulated by FAS and Tumor Necrosis Factor Receptor Activation
Authors: David Bryder, Veslemøy Ramsfjell, Ingunn Dybedal, Kim Theilgaard-Mönch, Carl-Magnus Högerkorp, Jörgen Adolfsson, Ole Johan Borge, Sten Eirik W. Jacobsen
Journal: The Journal of Experimental Medicine (2001)

Multipotent self-renewing hematopoietic stem cells (HSCs) are responsible for reconstitution of all blood cell lineages. Whereas growth stimulatory cytokines have been demonstrated to promote HSC self-renewal, the potential role of negative regulators remains elusive. Receptors for tumor necrosis factor (TNF) and Fas ligand have been implicated as regulators of steady-state hematopoiesis, and if overexpressed mediate bone marrow failure. However, it has been proposed that hematopoietic progenitors rather than stem cells might be targeted by Fas activation. Here, murine Lin−Sca1+c-kit+ stem cells revealed little or no constitutive expression of Fas and failed to respond to an agonistic anti-Fas antibody. However, if induced to undergo self-renewal in the presence of TNF-α, the entire short and long-term repopulating HSC pool acquired Fas expression at high levels and concomitant activation of Fas suppressed in vitro growth of Lin−Sca1+c-kit+ cells cultured at the single cell level. Moreover, Lin−Sca1+c-kit+ stem cells undergoing self-renewal divisions in vitro were severely and irreversibly compromised in their short- and long-term multilineage reconstituting ability if activated by TNF-α or through Fas, providing the first evidence for negative regulators of HSC self-renewal.
Immunobiology of the Maternal-Fetal Relationship
Authors: R E Rocklin, J L Kitzmiller, M D Kaye
Journal: Annual Review of Medicine (1979)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Endothelial cell orientation on aortic valve leaflets
Authors: J D. DECK
Journal: Cardiovascular Research (1986)

Journal Article Endothelial cell orientation on aortic valve leaflets Get access J DAVID DECK J DAVID DECK From the Department of Anatomy, School of Medicine, University of Virginia, Charlottesville, Virginia, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 20, Issue 10, October 1986, Pages 760–767, https://doi.org/10.1093/cvr/20.10.760 Published: 01 October 1986
Relative bioavailability of salbutamol to the lung following inhalation using metered dose inhalation methods and spacer devices.
Authors: M Hindle, H Chrystyn
Journal: Thorax (1994)

BACKGROUND--Inhalation aids do not require coordination between actuation of a metered dose inhaler (MDI) with inspiration and reduce oropharyngeal impaction. The delivery of salbutamol to the lung and systemic availability following inhalation with three commonly used spacers and an open mouth technique have been evaluated using a simple noninvasive technique based on urinary excretion 30 minutes and 24 hours after the dose. METHODS--Ten healthy subjects inhaled, on randomised study days, 4 x 100 micrograms from a Ventolin MDI and, subsequently, with the aid of a Volumatic, Bricanyl Spacer, and Nebuhaler spacer device. In addition, an open mouth inhaler technique was evaluated. Urine samples were collected 0-30 minutes and 0.5-24 hours after inhalation. From these samples the relative bioavailability to the lung (urinary salbutamol excretion 30 minutes after dosing) and the systemic bioavailability of the dose (24 hour urinary excretion of salbutamol and its metabolite) for each inhalation method was obtained. RESULTS--The mean (SD) urinary excretion of salbutamol 30 minutes after inhalation using the MDI alone and with the Volumatic, Bricanyl Spacer, Nebuhaler, and open mouth technique was 2.83 (0.78)%, 3.37 (0.69)%, 4.09 (0.91)%, 4.34 (1.60)%, and 3.49 (0.98)%, respectively, expressed as a percentage of the nominal dose. The nebuhaler and Bricanyl Spacer spacer devices were found to increase the relative bioavailability of salbutamol to the lung compared with the MDI alone. Compared with the MDI the inhalation aid increases were much greater than the intra-individual variability of the urinary excretion method. In 11 individuals who each repeated the same inhalation procedure on four separate occasions, the mean (SD) coefficient of variation was 8.24 (2.36)%. The mean (SD) 24 hour urinary excretion of salbutamol and its metabolites was 26.6 (6.79), 27.0 (7.95), and 55.6 (9.74)% of the salbutamol dose for the Volumatic, Nebuhaler, and MDI, respectively. Similar values following the open mouth method and Bricanyl Spacer were 48.9 (10.97)% and 43.8 (11.57)%. These values, representing the systemic availability of the inhaled dose, were lower when inhaling with the aid of the Volumatic and Nebuhaler than inhalation from the MDI alone. CONCLUSIONS--Spacer devices improve pulmonary bioavailability of salbutamol and reduce the systemically available dose.
Familial sarcoidosis presenting with stridor.
Authors: S Priestley, J C Delaney
Journal: Thorax (1981)

Sarcoidosis uncommonly presents with bronchial nar- rowing, produced by mucosal lesions or external com- pression by enlarged glands.We report two sisters with sarcoidosis who presented with severe inspiratory stridor as a result of obstruction of the major airways.An un- usual feature of the second case was unilateral glandular enlargement.This produced such severe obstruction that mechanical dilatation was necessary to relieve the dys- pnoea. Case reports PATIENT IA 26-year-old accounts clerk presented with a three- month history of increasing dyspnoea, non-productive cough, and lassitude.Although she smoked 20 cigarettes per day, there was no history of previous respiratory disease.On examination, she was severely breathless at rest, with a marked inspiratory stridor.The chest radio- graph showed bilateral hilar lymphadenopathy and pul- monary infiltrates.Tomograms confirmed the hilar
Comparison of Effectiveness of Autologous and Nonautologous Plasma in Oligemic Shock in Dogs
Authors: George L. Elias, Fraser N. Gurd, Lawrence G. Hampson, Arnold S. V. Burgen
Journal: Circulation Research (1962)

A comparison has been made between the effectiveness of nonautologous and autologous plasma as a plasma volume expander in dogs made severely oligemic by acute hemorrhage. No difference was found in their effectiveness in expanding plasma volume or in raising blood pressure. It is suggested that the reactions seen in normal dogs are suppressed in oligemic dogs by catecholamines liberated in response to hypotension.
Between Rho(k) and a Hard Place
Authors: Stephan Huveneers, Mat J.A.P. Daemen, Peter L. Hordijk
Journal: Circulation Research (2015)

Vascular stiffness is a mechanical property of the vessel wall that affects blood pressure, permeability, and inflammation. As a result, vascular stiffness is a key driver of (chronic) human disorders, including pulmonary arterial hypertension, kidney disease, and atherosclerosis. Responses of the endothelium to stiffening involve integration of mechanical cues from various sources, including the extracellular matrix, smooth muscle cells, and the forces that derive from shear stress of blood. This response in turn affects endothelial cell contractility, which is an important property that regulates endothelial stiffness, permeability, and leukocyte-vessel wall interactions. Moreover, endothelial stiffening reduces nitric oxide production, which promotes smooth muscle cell contraction and vasoconstriction. In fact, vessel wall stiffening, and microcirculatory endothelial dysfunction, precedes hypertension and thus underlies the development of vascular disease. Here, we review the cross talk among vessel wall stiffening, endothelial contractility, and vascular disease, which is controlled by Rho-driven actomyosin contractility and cellular mechanotransduction. In addition to discussing the various inputs and relevant molecular events in the endothelium, we address which actomyosin-regulated changes at cell adhesion complexes are genetically associated with human cardiovascular disease. Finally, we discuss recent findings that broaden therapeutic options for targeting this important mechanical signaling pathway in vascular pathogenesis.
Inverse Relationship between Human Papillomavirus-16 Infection and Disruptive<i>p53</i>Gene Mutations in Squamous Cell Carcinoma of the Head and Neck
Authors: William H. Westra, Janis M. Taube, M.L. Poeta, Shanaz Begum, David Sidransky, Wayne M. Koch
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Squamous cell carcinomas of the head and neck (HNSCC) often harbor p53 mutations, but p53 protein degradation by the viral oncoprotein E6 may supercede p53 mutations in human papillomavirus 16 (HPV16)–positive tumors. The prevalence of p53 mutations in HPV-positive HNSCCs is indeed lower, but in some tumors these alterations coexist. The purpose of this study was to discern whether HNSCCs differ in the type of p53 mutations as a function of HPV16 status. Experimental Design: The study was nested within a prospective multicenter study (ECOGE 4393/RTOG R9614) of patients with HNSCC treated surgically with curative intent. Tumors from one study center were used to construct a tissue microarray. The tumors were well characterized with respect to p53 mutational status. The tissue microarray was evaluated by HPV16 in situ hybridization. HPV16 analysis was also done on a select group of tonsillar carcinomas known to harbor disruptive p53 mutations defined as stop mutations or nonconservative mutations within the DNA binding domain. Results: HPV16 was detected in 12 of 89 (13%) HNSCCs. By tumor site, HPV16 was detected in 12 of 21 (57%) tumors from the palatine/lingual tonsils, but in none of 68 tumors from nontonsillar sites (P &amp;lt; 0.00001). Both HPV16-positive and HPV16-negative HNSCCs harbored p53 mutations (25% versus 52%), but disruptive mutations were only encountered in HPV16-negative carcinomas. Of seven tonsillar carcinomas with disruptive p53 mutations, none were HPV16 positive, in contrast to HPV16-positive tonsillar carcinomas without disruptive p53 mutations (0% versus 57%; P = 0.008). Conclusions: Although HPV16 and mutated p53 may coexist in a subset of HNSCCs, HPV16 and disruptive p53 mutations seem to be nonoverlapping events. A less calamitous genetic profile, including the absence of disruptive p53 mutations, may underlie the emerging clinical profile of HPV16-positive HNSCC such as improved patient outcome.
Noninvasive Ventilator Triggering in Chronic Obstructive Pulmonary Disease
Authors: IAN M. STELL, GRAHAM PAUL, KALOK C. LEE, JOSE PONTE, JOHN MOXHAM
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

To be most effective, noninvasive ventilation (NIV) ventilators should synchronize well with patients' breathing. However, the speed with which different ventilators can respond to the transitions between inspiration and expiration may vary, and abnormal respiratory mechanics and mask leaks may exacerbate this problem. This study explored synchronization using a new test lung model designed to simulate acute exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen ventilators were tested against different combinations of tidal volume (VT), airways resistance (Raw), FRC, and mask leak. These combinations ranged from those of a severe exacerbation of COPD, to a mild condition reflecting the optimal triggering conditions a ventilator is likely to encounter. The triggering delays from the beginning and end of "inspiration" of the test lung, to the appropriate responses from the ventilators were measured. Three of the ventilators had trigger delays less than approximately 120 ms at both the beginning and end of expiration under all conditions. Trigger delays of other ventilators were mainly in the range of 120 to 300 ms, although exceptionally as long as 500 ms. Varying the conditions had a variable but generally small effect on triggering times, suggesting that there is a largely unavoidable element to the triggering delays intrinsic to the design of the ventilators.
Associations of IL6 polymorphisms with lung function decline and COPD
Authors: J-Q He, M G Foreman, K Shumansky, X Zhang, L Akhabir, D D Sin, S F P Man, D L DeMeo, A A Litonjua, E K Silverman, J E Connett, N R Anthonisen, R A Wise, P D Pare, A J Sandford
Journal: Thorax (2009)

<h3>Background:</h3> Interleukin-6 (IL6) is a pleiotropic pro-inflammatory and immunomodulatory cytokine which probably plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). There is a functional single nucleotide polymorphism (SNP), -174G/C, in the promoter region of <i>IL6</i>. It was hypothesised that <i>IL6</i> SNPs influence susceptibility for impaired lung function and COPD in smokers. <h3>Methods:</h3> Seven and five SNPs in <i>IL6</i> were genotyped in two nested case-control samples derived from the Lung Health Study (LHS) based on phenotypes of rate of decline of forced expiratory volume in 1 s (FEV<sub>1</sub>) over 5 years and baseline FEV<sub>1</sub> at the beginning of the LHS. Serum IL6 concentrations were measured for all subjects. A partially overlapping panel of nine <i>IL6</i> SNPs was genotyped in 389 cases of COPD from the National Emphysema Treatment Trial (NETT) and 420 controls from the Normative Aging Study (NAS). <h3>Results:</h3> In the LHS, three <i>IL6</i> SNPs were associated with decline in FEV<sub>1</sub> (0.023⩽p⩽0.041 in additive models). Among them, the <i>IL6</i>_-174C allele was associated with a rapid decline in lung function. The association was more significant in a genotype-based analysis (p = 0.006). In the NETT-NAS study, <i>IL6</i>_-174G/C and four other <i>IL6</i> SNPs, all of which are in linkage disequilibrium with <i>IL6</i>_-174G/C, were associated with susceptibility to COPD (0.01⩽p⩽0.04 in additive genetic models). <h3>Conclusion:</h3> The results suggest that the <i>IL6</i>_-174G/C SNP is associated with a rapid decline in FEV<sub>1</sub> and susceptibility to COPD in smokers.
Molecular Changes in Tamoxifen-Resistant Breast Cancer: Relationship Between Estrogen Receptor, HER-2, and p38 Mitogen-Activated Protein Kinase
Authors: M. Carolina Gutierrez, Simone Detre, Stephen Johnston, Syed K. Mohsin, Jiang Shou, D. Craig Allred, Rachel Schiff, C. Kent Osborne, Mitch Dowsett
Journal: Journal of Clinical Oncology (2005)

To evaluate growth factor receptor cross talk with the estrogen receptor (ER) in paired clinical breast cancer specimens and in a xenograft model before tamoxifen and at tumor progression as a possible mechanism for tamoxifen resistance.Specimen pairs from 39 patients were tissue arrayed and stained for ER, progesterone receptor (PgR), Bcl-2, c-ErbB2 (HER-2), and phosphorylated (p) p38 mitogen-activated protein kinase (MAPK), p-ERK1/2 MAPK, and p-Akt. Xenograft MCF-7 tumors before and after tamoxifen resistance were assessed for levels of p-p38.Pretreatment, there were strong correlations between ER, PgR, and Bcl-2, and an inverse correlation between ER and HER-2. These correlations were lost in the tamoxifen- resistant tumors and replaced by strong correlations between ER and p-p38 and p-ERK. ER expression was lost in 17% of resistant tumors. Three (11%) of the 26 tumors originally negative for HER-2 became amplified and/or overexpressed at resistance. All ER-positive tumors that overexpressed HER-2 originally or at resistance expressed high levels of p-p38. In the pretreatment and tamoxifen-resistant specimens, there were strong correlations between p-p38 and p-ERK. In the tamoxifen-resistant xenograft tumors, like the clinical samples, there was a striking increase in p-p38.The molecular pathways driving tumor growth can change as the tumor progresses. Crosstalk between ER, HER-2, p38, and ERK may contribute to tamoxifen resistance and may provide molecular targets to overcome this resistance.
Exogenous Microparticles of Iron Oxide Bind to Activated Endothelial Cells but, Unlike Monocytes, Do Not Trigger an Endothelial Response
Authors: Andrew Jefferson, Neil Ruparelia, Robin P Choudhury
Journal: Theranostics (2013)

Targeting particles to sites of inflammation is of considerable interest for applications relating to molecular imaging and drug delivery.We and others have described micron-sized particles of iron oxide (MPIO) that can be directed using specific ligands (e.g.antibodies, peptides and oligosaccharides) to bind to mediators of vascular inflammation in vivo.Since leukocyte binding to these molecules can induce changes in the target cell, an outstanding question has been whether the binding of imaging particles to these mediators induces biologically significant changes in the endothelial cells, potentially initiating or propagating inflammation.Here, we address these questions by looking for changes in endothelial cells following binding of contrast agent.Specifically, we have quantified calcium flux, rearrangement of the actin cytoskeleton, production of reactive oxygen species (ROS), apoptosis and potential secondary changes, such as changes in gene and protein expression follow binding events to primary endothelial cells in vitro.Although leukocytes induced changes to endothelial cell function, we did not see any significant changes to endothelial calcium flux, cytoskeletal organisation, production of ROS or induction of apoptosis in response to antibody-MPIO binding.Furthermore, there were no changes to gene expression monitored via real-time RT-PCR or presentation of protein on the cell surface measured using flow cytometry.Our experiments demonstrate that whilst antibody-targeted microparticles mimic the binding capability of leukocytes to inflamed endothelium, they do not trigger the same cellular responses and do not appear to initiate or compound inflammation.These properties are desirable for targeted therapeutic and diagnostic agents.