tbuckley/cabot-search huggingface dataset:
H-Ras Regulates Angiogenesis and Vascular Permeability by Activation of Distinct Downstream Effectors
Authors: Doinita Serban, Jie Leng, David Cheresh
Journal: Circulation Research (2008)

Angiogenesis and vascular permeability occur following endothelium activation by vascular endothelial growth factor (VEGF). Downstream mechanisms that define these vascular responses remain unknown. H-Ras activation has been associated with the angiogenic response. However, active H-Ras initiates a wide spectrum of other biological responses through multiple downstream effectors. To identify vascular signaling by H-Ras and the immediate effectors we activated the extracellular signal regulated kinase/mitogen-activated protein kinase or phosphatidylinositol 3-kinase (PI3K) pathways in chicken and mouse endothelial tissues by ectopic expression of the Ras effector mutants H-RasV12S35 or H-RasV12C40, respectively. Constitutive activation of the extracellular signal-regulate kinase/mitogen-activated protein kinase pathway by H-RasV12S35 was sufficient to induce angiogenesis and not vascular permeability, whereas activation of the PI3K pathway by H-RasV12C40 was required for both angiogenesis and vascular permeability. Pharmacological inhibition of PI3K (alpha/beta) suppressed both Ras- or VEGF-mediated vascular response in vivo and survival of primary human endothelial cells in vitro. However, inhibition of PI3K (gamma/delta) suppressed Ras- or VEGF-mediated vascular permeability in vivo, with no effect on survival of primary endothelial cells. This was supported by genetic studies because PI3K p110gamma knockout mice showed impaired vascular permeability response to VEGF or H-RasV12C40 treatment yet produced a wild-type angiogenic response to H-RasV12S35. We conclude that downstream of VEGF, H-Ras serves as a cellular switch that controls neovascularization and vascular permeability by activation of distinct effectors.
Overexpression of steroidogenic acute regulatory protein increases macrophage cholesterol efflux to apolipoprotein AI
Authors: Janice M.W. Taylor, Faye Borthwick, Chris Bartholomew, Annette Graham
Journal: Cardiovascular Research (2010)

In this study, we investigated the impact of enhancing cholesterol delivery to mitochondrial sterol 27-hydroxylase, via steroidogenic acute regulatory protein (StAR), on the expression of genes involved in macrophage cholesterol homeostasis and efflux of cholesterol to apolipoprotein (apo) AI. Stably transfected, murine (RAW 264.7) macrophages were used to investigate the role of StAR in cholesterol homeostasis. Cellular responses were analysed using quantitative PCR, immunoblotting, and an LXRE reporter plasmid; [3H]cholesterol efflux was measured in the presence or absence of apoAI. Macrophage overexpression of mitochondrial cholesterol trafficking protein, StAR, activates and induces expression of liver X receptors (LXRs), and significantly alters expression of genes involved in cholesterol homeostasis, decreasing Fdps, Hmgcr, Mvk, Ldlr, and Scap, and markedly increasing Abca1 mRNA and protein. Overexpression of StAR, but not mutated 'loss-of-function' (R181L) StAR, enhanced efflux of [3H]cholesterol to apoAI, and this effect was maintained in macrophages pretreated with LDL or acetylated LDL. The effect of StAR overexpression on apoAI-dependent [3H]cholesterol efflux was mimicked by non-sterol agonist, T901317, and 27-hydroxycholesterol, and blocked by LXR inhibitor, geranylgeranyl pyrophosphate, sterol 27-hydroxylase inhibitor, GW273297x, and probucol, inhibitor of ATP binding cassette transporter A1 (ABCA1). Importantly, all observed effects of StAR overexpression were dependent upon cyclic AMP (cAMP analogue, dibutyryl cAMP), which is required for the full activity of the StAR protein to be manifested. Macrophage overexpression of StAR significantly enhances LXR-dependent apoAI- and ABCA1-dependent cholesterol efflux, by which disposal of excess arterial cholesterol deposits and atheroma regression can be achieved.
Humoral and cell-mediated autoimmunity in allergy to Aspergillus fumigatus.
Authors: R Crameri, A Faith, S Hemmann, R Jaussi, C Ismail, G Menz, K Blaser
Journal: The Journal of Experimental Medicine (1996)

A cDNA encoding an allergenic protein was isolated from an Aspergillus fumigatus (A. fumigatus) cDNA library displayed on the surface of filamentous phage. Serum immunoglobulin E (IgE) from A. fumigatus-sensitized individuals was used to enrich phage-expressing gene products binding to IgE. One of the cDNAs encoded a 26.7-kD protein that was identified as a manganese superoxide dismutase (MnSOD) sharing 51.5% identity and 67.2% homology to the corresponding human enzyme. Both human and A. fumigatus MnSOD coding sequences were expressed in Escherichia coli as [His]6-tagged fusion proteins and purified by Ni(2+)-chelate affinity chromatography. The two recombinant MnSODs were both recognized by IgE antibodies from subjects allergic to the A. fumigatus MnSOD and elicited specific immediate type allergic skin reactions in these individuals. Moreover, both human and A. fumigatus MnSOD induced proliferation in peripheral blood mononuclear cells of A. fumigatus-allergic subjects who showed specific IgE responses and reacted in skin tests to MnSOD. These observations provide evidence for autoreactivity to the human MnSOD in allergic persons sensitized to an environmental allergen from A. fumigatus who share a high degree of sequence homology to the corresponding human enzyme.
Renal effects of oral prostaglandin supplementation after ibuprofen in diabetic subjects
Authors: G L Bakris, U Starke, M Heifets, D Polack, M Smith, S Leurgans
Journal: Journal of the American Society of Nephrology (1995)

Prostaglandins of the E series (PGE) are known to contribute to the maintenance of renal hemodynamics in subjects with chronic renal insufficiency. Agents that block PGE synthesis, nonsteroidal anti-inflammatory agents (NSAID), are widely used by people with renal insufficiency. This study was undertaken in subjects with renal insufficiency secondary to diabetes to evaluate the acute effects of a PGE1 analog, misoprostol, on NSAID-induced changes in RBF, as calculated by para-aminohippurate clearance, and GFR, as calculated by inulin clearance. Sodium excretion was also assessed. Twenty-five fasting subjects with a mean age of 56 +/- 4 yr received 800 mg of ibuprofen orally. A concomitant dose of either a placebo (PL) or 200 micrograms of misoprostol was also given. This was followed in 1 h by either a placebo or an additional 200-micrograms dose of misoprostol. Measurements for the determination of RBF, GFR, blood pressure, and fractional excretion of sodium were performed every 30 min for the next 5 h. The greatest reduction in both GFR (-25 +/- 7 mL/min per 1.73 m2 PL versus -10 +/- 4 mL/min per 1.73 m2, misoprostol delta GFR; P < 0.05) and RBF (-48 +/- 21 mL/min per 1.73 m2 PL versus -15 +/- 8 mL/min per 1.73 m2, M delta RBF; P < 0.05) occurred approximately 2 h after the NSAID dose. No significant differences were noted in blood pressure, fractional excretion of sodium, or other measured parameters between groups during the entire study. Gastrointestinal upset was the most common side effect observed in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Double sodium and potassium sulphates revealed by microprobe analysis in dried cervical mucus: a mid-cycle crystallographic index
Authors: J Berthou
Journal: Human Reproduction Update (1997)

The use of physical techniques such as scanning electron microscopy and microprobe analysis permits the analysis of valuable details of the structure of dried samples of mid-cycle cervical mucus during the period of maximum ferning. From a crystallographic point of view, particular attention was paid to the location, morphology and chemical composition of anisotropic organic sulphate microstructures. As distinct from the isotropic sodium chloride pattern described by Papanicolaou, these appear in a narrow period of time corresponding to the middle of the period of maximum ferning. Anisotropic microstructures were revealed to be tiny isolated crystals or polycrystalline aggregates composed of double salts of potassium and sodium. The potassium/sodium cation ratio, equal to 3/1, was constant in the best specimens. Using a simple polarizing microscope, the detection of anisotropic microstructures may be useful to determine the period of maximum fertility more accurately. In addition, experiments have been carried out in order to determine the relative importance of sulphate anisotropic structures as compared with the whole crystallized surface and to investigate precisely their transience after they appear.
Mast cells are an important cellular source of tumour necrosis factor α in human intestinal tissue
Authors: S C Bischoff, A Lorentz, S Schwengberg, G Weier, R Raab, M P Manns
Journal: Gut (1999)

BACKGROUND Several inflammatory disorders of the intestine are characterised by enhanced expression of tumour necrosis factor α (TNF-α). Monocytes and macrophages have been suggested as a major cellular source of TNF-α in human gut, whereas mast cells, although known to be capable of producing TNF-α, have been poorly examined in this respect. AIMS To investigate whether human intestinal mast cells can produce TNF-α, and which factors regulate TNF-α production in these cells. METHODS Mast cells were isolated from surgery tissue specimens of patients undergoing bowel resection because of cancer. Immunohistochemical studies were performed in biopsy specimens derived from 13 patients (two healthy controls, four with Crohn’s disease, four with ulcerative colitis, three others). TNF-α mRNA and protein expression were studied in vitro by polymerase chain reaction, RNAse protection assay, western blot, and enzyme linked immunosorbent assay in isolated purified human intestinal mast cells stimulated by IgE receptor crosslinking, intestinal bacteria, and lipopolysaccharide. Cellular localisation of TNF-α was examined by immunohistochemistry. RESULTS TNF-α mRNA and protein were expressed constitutively in isolated human intestinal mast cells. Expression of TNF-α mRNA and release of TNF-α protein were substantially enhanced by IgE receptor crosslinking and by coculture of mast cells with intestinal bacteria; lipopolysaccharide had only marginal effects. Immunohistochemical studies revealed that approximately 60% of the lamina propria cells with immunoreactivity for TNF-α were mast cells. CONCLUSIONS The data show that mast cells are an important source of TNF-α in the human intestinal mucosa.
Football injuries in Oslo: a one-year study.
Authors: S. Maehlum, O. A. Daljord
Journal: British Journal of Sports Medicine (1984)

All football injuries treated at the Emergency Department, Oslo City Hospital, 1329 patients, 1167 males and 162 females, were recorded for one year, accounting for 28.4% of all sports injuries. Most injuries seen were in the 15-19 years age group in females and 20-24 years age group in males; 68% of the females and 42% of the males (p less than 0.001) were below 20 years of age, and 87% of the injuries occurred in competitive football. During matches, 695 players were injured giving an incidence of 34.5 injuries/10,000 player matches. The injuries occurred all year with a peak in June. Sprains accounted for 41% of the injuries, 23% were contusions and 19% fractures. Most injuries (59%) affected the legs. Hospital admission was required for three females and 57 males. The football injuries required 1966 consultations and necessitated that 349 patients had to stay away from work for a total of 6137 days.
MEDI-563, a humanized anti–IL-5 receptor α mAb with enhanced antibody-dependent cell-mediated cytotoxicity function
Authors: Roland Kolbeck, Alexander Kozhich, Masamichi Koike, Li Peng, Cecilia K. Andersson, Melissa M. Damschroder, Jennifer L. Reed, Robert Woods, William W. Dall'Acqua, Geoffrey L. Stephens, Jonas S. Erjefalt, Leif Bjermer, Alison A. Humbles, David Gossage, Herren Wu, Peter A. Kiener, George L. Spitalny, Charles R. Mackay, Nestor A. Molfino, Anthony J. Coyle
Journal: Journal of Allergy and Clinical Immunology (2010)
High-Energy Shock Waves Enhance Hyperthermic Response of Tumors: Effects on Blood Flow, Energy Metabolism, and Tumor Growth
Authors: M. Dellian, S. Walenta, F. Gamarra, G. E. H. Kuhnle, W. Mueller-Klieser, A. E. Goetz
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article High-Energy Shock Waves Enhance Hyperthermic Response of Tumors: Effects on Blood Flow, Energy Metabolism, and Tumor Growth Get access Marc Dellian, Marc Dellian Search for other works by this author on: Oxford Academic PubMed Google Scholar Stefan Walenta, Stefan Walenta Search for other works by this author on: Oxford Academic PubMed Google Scholar Fernando Gamarra, Fernando Gamarra Search for other works by this author on: Oxford Academic PubMed Google Scholar Gerhard E. H. Kuhnle, Gerhard E. H. Kuhnle Search for other works by this author on: Oxford Academic PubMed Google Scholar Wolfgang Mueller-Klieser, Wolfgang Mueller-Klieser Search for other works by this author on: Oxford Academic PubMed Google Scholar Alwin E. Goetz Alwin E. Goetz * * Correspondence to: A. E. Goetz, M.D., Institute of Anesthesiology. Klinikum Grosshadern. Ludwig-Maximilians-University. Marchioninistr. 15. D-81366 Munich, FRG. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 4, 16 February 1994, Pages 287–293, https://doi.org/10.1093/jnci/86.4.287 Published: 16 February 1994 Article history Received: 08 July 1993 Revision received: 09 November 1993 Accepted: 17 November 1993 Published: 16 February 1994
Apical Cell Membranes Are Shed into Urine from Injured Podocytes
Authors: Masanori Hara, Toshio Yanagihara, Itaru Kihara, Kazuhiro Higashi, Kotarou Fujimoto, Tadahiro Kajita
Journal: Journal of the American Society of Nephrology (2005)

Previously it was shown that urine from patients with nephritis contains podocytes and their fragments (podocalyxin [PCX]-positive granular structures [PPGS]), reflecting the degree of podocyte injury. The present study was designed to trace PPGS to their origin. Urine samples and renal biopsy specimens from 53 children with nephrotic syndrome and nephritis were examined immunohistochemically. Immunofluorescence studies of kidney sections using an anti-PCX antibody demonstrated that PPGS originated from the glomerulus and flowed into the tubular lumen. Electron microscopic examination revealed that PPGS originated from microvillous or vesicle-like structures on injured podocytes in the glomerulus. For examining the origin of the PPGS, apical, slit-diaphragmatic, and basal portions of the podocytes were specifically stained, revealing that PPGS are composed primarily of apical podocyte membranes. Several newly developed antibodies that are reactive with various segments of the PCX molecule were used to analyze more detailed membrane structures, and it was found that PPGS contained intact PCX molecules, indicating that cell membrane structures are excreted in urine. The quantification of PCX content and podocyte numbers revealed that urinary sediment PCX (u-sed-PCX) content per urinary podocyte was much higher than PCX content per podocyte from isolated glomeruli of normal controls, suggesting that u-sed-PCX are derived from sources other than just the cell debris of detached podocytes. Analysis of the correlation between u-sed-PCX and renal histology revealed that the presence of PPGS reflects acute glomerular injury. In conclusion, podocyte apical cell membranes are shed into the urine from injured podocytes, indicating a previously unrecognized manifestation of podocyte injury.
Sustained Complete Responses in Patients With Lymphoma Receiving Autologous Cytotoxic T Lymphocytes Targeting Epstein-Barr Virus Latent Membrane Proteins
Authors: Catherine M. Bollard, Stephen Gottschalk, Vicky Torrano, Oumar Diouf, Stephanie Ku, Yasmin Hazrat, George Carrum, Carlos Ramos, Luis Fayad, Elizabeth J. Shpall, Barbara Pro, Hao Liu, Meng-Fen Wu, Daniel Lee, Andrea M. Sheehan, Youli Zu, Adrian P. Gee, Malcolm K. Brenner, Helen E. Heslop, Cliona M. Rooney
Journal: Journal of Clinical Oncology (2013)

Tumor cells from approximately 40% of patients with Hodgkin or non-Hodgkin lymphoma express the type II latency Epstein-Barr virus (EBV) antigens latent membrane protein 1 (LMP1) and LMP2, which represent attractive targets for immunotherapy. Because T cells specific for these antigens are present with low frequency and may be rendered anergic by the tumors that express them, we expanded LMP-cytotoxic T lymphocytes (CTLs) from patients with lymphoma using autologous dendritic cells and EBV-transformed B-lymphoblastoid cell lines transduced with an adenoviral vector expressing either LMP2 alone (n = 17) or both LMP2 and ΔLMP1 (n = 33).
A thousand years of pulmonary medicine: good news and bad
Authors: J.F. Murray
Journal: European Respiratory Journal (2001)

I should like to start by thanking Professor Gibson and all members of the Programme Committee for asking me to give this Millennial Lecture. I am, of course, greatly honoured at having been chosen for this, a once every one-thousand years event. One of the things Professor Gibson refrained from saying in his overly flattering introduction is that I actually started my medical career back in the first half of the last century, a long time ago. So I have been witness to over50 years of medical progress – and what a half century it has been! But that is not what I am going to talk about.

What I propose to do this morning is, first of all, to discuss briefly some of the remarkable achievements in pulmonary medicine and the men and women who made them during the recently departed millennium. Consequently, I will start my review in the year 1000. Then, I will reflect on the evolution and present deplorable status of two of mankind's deadliest scourges, both of them chiefly pulmonary disorders, one practically as old as human beings themselves, and the other practically brand new. And finally, I will make some suggestions as to how the members of the societies that are sponsoring this World Congress on Lung Health can help solve a few of the existing problems. May I remind you that as the title of my talk indicates, I bring you both good news and bad news.

The year 1000 marked the end in Europe of the formless Dark Ages and the beginning of the slightly more progressive Medieval Period; culture and enlightenment were considerably more advanced in Asia at the time. There isn't much information available about ordinary life in Europe in the year 1000, but it has been characterized as “unimaginably …
Previously undiagnosed obesity hypoventilation syndrome
Authors: J K Quint, L Ward, A G Davison, C. A De Boeck
Journal: Thorax (2007)

There are approximately 300 million obese individuals (body mass index (BMI) 30 kg/m2 or higher) worldwide,1 and in the UK nearly one quarter of all adults are classified as clinically obese.2 Obesity hypoventilation syndrome (OHS) describes a subgroup of obese individuals who develop chronic daytime hypercapnia (arterial carbon dioxide tension (Paco2) >6 kPa) and hypoxia (arterial oxygen tension (Pao2) <8 kPa) in the absence of chronic obstructive pulmonary disease (COPD).3,4 Presentation is usually indolent, with symptoms arising due to hypercapnia and sustained hypoventilation (hypersomnolence, alterations in cognitive function, headache, peripheral oedema, hypertension, congestive cardiac failure).5 At Southend Hospital we have noticed an increase in acute admissions in obese individuals with type II respiratory failure of initially unknown cause in whom a diagnosis of OHS was eventually made.

We collected data on 11 patients (seven men) diagnosed with OHS from 1996 to 2005 from the respiratory disease register. Patients with possible overlap syndrome were excluded (smokers with forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio <70%). Patient demographics, lung function and Epworth sleep score (ESS) were documented. The results of initial sleep studies on air were analysed. Initial management was recorded and follow-up data were reviewed regarding ESS, blood gases, long-term use of continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV, using bi-level pressure support ventilation).

The mean (SD) age of the 11 patients was 59 (12) years and the mean (SD) BMI was 52.7 (16.6) kg/m2 (range 37–102). Two patients were current smokers, one an ex-smoker and …
Sex Differences in Major Bleeding With Glycoprotein IIb/IIIa Inhibitors
Authors: Karen P. Alexander, Anita Y. Chen, L. Kristin Newby, Janice B. Schwartz, Rita F. Redberg, Judith S. Hochman, Matthew T. Roe, W. Brian Gibler, E. Magnus Ohman, Eric D. Peterson
Journal: Circulation (2006)

Glycoprotein (GP) IIb/IIIa inhibitors are beneficial in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS); their safe use in women, however, remains a concern. The contribution of dosing to the observed sex-related differences in bleeding is unknown.We explored the relationship between patient sex, GP IIb/IIIa inhibitor use, dose, and bleeding in 32 601 patients with NSTE ACS across 400 CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) hospitals, of whom 18 436 were treated. GP IIb/IIIa inhibitor dose was defined as excessive if not reduced when creatinine clearance was < 50 mL/min for eptifibatide or < 30 mL/min for tirofiban. Major bleeding was defined as a hematocrit drop > or = 0.12, need for transfusion, or intracranial bleeding. Major bleeding was adjusted for clinical factors and antithrombotic dose. The risk for bleeding attributable to excess GP IIb/IIIa dose was determined by sex using prevalence and adjusted odds ratios (ORs). Women had higher rates of major bleeding than men among those treated with GP IIb/IIIa inhibitors (15.7% versus 7.3%, P<0.0001) and among those not treated (8.5% versus 5.4%, P<0.0001). Despite similar serum creatinine levels, creatinine clearance averaged 20 points lower among treated women than men. Treated women were also more likely to receive excess GP IIb/IIIa doses than men (46.4% versus 17.2%, P<0.0001; adjusted OR 3.81, 95% confidence interval [CI] 3.39 to 4.27). Excess dosing was associated with increased risk of bleeding in women (OR 1.72, 95% CI 1.30 to 2.28) and men (OR 1.27, 95% CI 0.97 to 1.66); however, bleeding risk attributable to dosing was much higher in women (25.0% versus 4.4%).Women experience more bleeding than men whether or not they are treated with GP IIb/IIIa inhibitors; however, because of frequent excessive dosing in women, up to one fourth of this sex-related risk difference in bleeding is avoidable. Appropriate dosing will improve care of all patients with NSTE ACS, with a particular benefit for women.