tbuckley/cabot-search huggingface dataset:
Effect of alveolar pressure on pulmonary artery pressure in chronically hypoxic rats
Authors: R WACH, C J EMERY, D BEE, G R BARER
Journal: Cardiovascular Research (1987)

The effect on pulmonary artery pressure of a rise in alveolar pressure differed in chronically hypoxic rats (10% O2 for 3-5 weeks) compared with control rats. Chronically hypoxic rats have newly muscularised walls in arterioles in the alveolar region. Isolated lungs of chronically hypoxic and control rats were perfused with blood under conditions in which alveolar pressure was greater than left atrial pressure during both normoxia and hypoxia. Alveolar pressure was the effective downstream pressure. Pressure-flow lines were measured at low and high alveolar pressure (5 and 15 mmHg). During normoxia pressure-flow lines of chronically hypoxic rats had a steeper slope (higher resistance) and greater extrapolated intercept on the pressure axis (effective downstream pressure) than control rats. In both groups of rats the change from low to high alveolar pressure during normoxia caused an approximately parallel shift in the pressure-flow line similar to the change in alveolar pressure. During hypoxia, which led to an increase in slope and intercept in both groups of rats, the effect of a rise in alveolar pressure differed in chronically hypoxic from control rats. In control rats there was a small parallel shift in the pressure-flow line that was much less than the increase in alveolar pressure; in chronically hypoxic rats there was a large parallel shift in the pressure-flow line that was greater than the increase in alveolar pressure. Thus in chronically hypoxic rats hypoxic vasoconstriction probably occurred mainly in muscular alveolar vessels, whereas in control rats it probably occurred upstream in extra-alveolar vessels. At constant blood flow the relation between pulmonary artery pressure and alveolar pressure was measured while alveolar pressure was reduced from approximately 15 mmHg to zero during both normoxia and hypoxia. In control and chronically hypoxic rats the slope of this line was less than 1. At an alveolar pressure of 2-3 mmHg there was an inflection point below which the line was nearly horizontal in control but negative in chronically hypoxic rats. During hypoxia the inflection point increased in control but not in chronically hypoxic rats, whereas the preinflection slope became negative. Apart from a rise in pulmonary artery pressure at all values of alveolar pressure, which occurred in both groups of rats, there was no change in the form of the curve in chronically hypoxic rats during hypoxia. These results also suggest constriction of extra-alveolar vessels in control rats and alveolar vessels in chronically hypoxic rats during hypoxia.
RPN2-mediated glycosylation of tetraspanin CD63 regulates breast cancer cell malignancy
Authors: Naoomi Tominaga, Keitaro Hagiwara, Nobuyoshi Kosaka, Kimi Honma, Hitoshi Nakagama, Takahiro Ochiya
Journal: Molecular Cancer (2014)

The tetraspanin CD63 is a highly N-glycosylated protein that is known to regulate cancer malignancy. However, the contribution of glycosylation of CD63 to cancer malignancy remains unclear. Previously, we reported that ribophorin II (RPN2), which is part of an N-oligosaccharyle transferase complex, is responsible for drug resistance in breast cancer cells. In this study, we demonstrate that cancer malignancy associated with the glycosylation of CD63 is regulated by RPN2. Inhibition of RPN2 expression led to a reduction in CD63 glycosylation. In addition, the localization of CD63 was deregulated by knockdown of RPN2. Interestingly, multidrug resistance protein 1 (MDR1) localization was displaced from the cell surface in CD63-silenced cells. CD63 silencing reduced the chemoresistance and invasion ability of malignant breast cancer cells. Furthermore, the enrichment of CD63/MDR1-double positive cells was associated with lymph node metastasis. Taken together, these results indicated that high glycosylation of CD63 by RPN2 is implicated in clinical outcomes in breast cancer patients. These findings describe a novel and important function of RPN2-mediated CD63 glycosylation, which regulates MDR1 localization and cancer malignancy, including drug resistance and invasion.
Emergency Aortocoronary Bypass for Impending or Extending Myocardial Infarction
Authors: J. DONALD HILL, WELLIAM J. KERTH, JOHN J. KELLY, ARTHUR SELZER, WILLIAM ARMSTRONG, ROBERT W. POPPER, MANLY F. LANGSTON, KEITH E. COHN
Journal: Circulation (1971)

Emergency coronary arteriography and aortocoronary bypass were successfully performed in three patients with preinfarction angina. Four patients with impending extension of a recent infarction died during or after aortocoronary bypass surgery. Aortocoronary bypass may improve angina and prevent infarction in selected instances of preinfarction angina. In patients with recent infarction and impending extension the risk of surgery appears to be prohibitively high.
Cord blood transplantation combined with rituximab for Wiskott-Aldrich syndrome with autoimmune thrombotic thrombocytopenic purpura
Authors: Hidemi Toyoda, Eiichi Azuma, Yukako Kawasaki, Tadashi Iwasa, Hiroyuki Ohashi, Shoichiro Otsuki, Shotaro Iwamoto, Masahiro Hirayama, Naomi Itoh-Habe, Hideo Wada, Mineo Kondo, Yoshitaka Keida, Tsuyoshi Ito, Yoshihiro Komada
Journal: Journal of Allergy and Clinical Immunology (2013)
Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies
Authors: Craig Anderson, Koon Teo, Peggy Gao, Hisatomi Arima, Antonio Dans, Thomas Unger, Patrick Commerford, Leanne Dyal, Helmut Schumacher, Janice Pogue, Ernesto Paolasso, Nicolaas Holwerda, Irina Chazova, Azan Binbrek, James Young, Salim Yusuf
Journal: The Lancet Neurology (2010)
Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma
Authors: Koen Van Besien, Fausto R. Loberiza, Ruta Bajorunaite, James O. Armitage, Asad Bashey, Linda J. Burns, Cesar O. Freytes, John Gibson, Mary M. Horowitz, David J. Inwards, David I. Marks, Rodrigo Martino, Richard T. Maziarz, Arturo Molina, Santiago Pavlovsky, Andrew L. Pecora, Harry C. Schouten, Thomas C. Shea, Hillard M. Lazarus, J. Douglas Rizzo, Julie M. Vose
Journal: Blood (2003)
HIF-1 Inhibits Mitochondrial Biogenesis and Cellular Respiration in VHL-Deficient Renal Cell Carcinoma by Repression of C-MYC Activity
Authors: Huafeng Zhang, Ping Gao, Ryo Fukuda, Ganesh Kumar, Balaji Krishnamachary, Karen I. Zeller, Chi V. Dang, Gregg L. Semenza
Journal: Cancer Cell (2007)
A Large Variation in the Rates of Synonymous Substitution for RNA Viruses and Its Relationship to a Diversity of Viral Infection and Transmission Modes
Authors: Kousuke Hanada, Yoshiyuki Suzuki, Takashi Gojobori
Journal: Molecular Biology and Evolution (2004)

RNA viruses successfully adapt to various environments by repeatedly producing new mutants, often through generating a number of nucleotide substitutions. To estimate the degree of variation in mutation rates of RNA viruses and to understand the source of such variation, we studied the synonymous substitution rate because synonymous substitution is exempt from functional constraints at the protein level, and its rate reflects the mutation rate to a great extent. We estimated the synonymous substitution rates for a total of 49 different species of RNA viruses, and we found that the rates had tremendous variation by 5 orders of magnitude (from 1.3 × 10−7 to 6.2 × 10−2 /synonymous site/year). Comparing the synonymous substitution rates with the replication frequencies and replication error rates for the RNA viruses, we found that the main source of the rate variation was differences in the replication frequency because the rates of replication error were roughly constant over different RNA viruses. Moreover, we examined a relationship between viral life strategies and synonymous substitution rates to understand which viral life strategies affect replication frequencies. The results show that the variation of synonymous substitution rates has been influenced most by either the difference in the infection modes or the differences in the transmission modes. In conclusion, the variation of mutation rates for RNA viruses is caused by different replication frequencies, which are affected strongly by the infection and transmission modes.
Decreased cardiac activity of AMP deaminase in subjects with the AMPD1 mutation—A potential mechanism of protection in heart failure
Authors: K Kalsi
Journal: Cardiovascular Research (2003)

Possession of the C34T (Glu12Stop) nonsense mutation in the AMP-deaminase 1 (AMPD1) gene has been shown to be associated with improved prognosis in heart failure and ischemic heart disease. The most likely event leading to these clinical effects is a reduced capacity of the AMP deamination pathway and increased production of cardio-protective adenosine. However, since AMPD1 is predominantly expressed in skeletal muscle, the protective effects could be related not only to local cardiac changes, but also to a systemic mechanism. In the present study we evaluated the effect of the C34T mutation on cardiac AMP-deaminase activity and on the systemic changes in adenosine production.The presence of the C34T mutation was assayed by single-stranded conformational polymorphism (SSCP). Analysis of the AMPD1 genotype and measurement of enzyme activities was performed on 27 patients with heart failure (HF). In addition, blood adenosine concentration was measured by liquid chromatography/mass spectrometry (LC/MS) in 21 healthy subjects with established AMPD1 genotype at rest and following exhaustive exercise.Cardiac AMP-deaminase activity in heterozygotes (C/T) was 0.59+/-0.02 nmol/min/g wet wt-about half of the activity found in normal wild-type (C/C) individuals (1.06+/-0.09 nmol/min/g wet wt, P=0.003). There were no significant differences in the activities of any other enzymes between subjects with the C/T or C/C genotype. Resting venous blood adenosine concentration was similar in subjects with C/C, C/T and homozygous for the mutated allele (T/T) genotype. Following exercise, a significant increase in adenosine was observed in T/T subjects (by 0.013+/-0.009 micromol/l, P=0.035) but not in C/C (0.003+/-0.009 micromol/l) or C/T (-0.002+/-0.011 micromol/l).Our findings indicate that the C34T mutation of AMPD1 leads to a decrease in cardiac enzyme activity of AMP-deaminase without changes in any other adenosine-regulating enzymes, highlighting the importance of local cardiac metabolic changes. Systemic (blood) changes in adenosine concentration were apparent only in homozygous subjects and therefore may play a relatively small part in cardio-protection.
S47 Pseudomonas aeruginosa induces apoptosis in human dendritic cells: a potential mechanism to evade pulmonary immune responses
Authors: H. K. Bayes, T. Evans
Journal: Thorax (2011)

<h3>Introduction</h3> Airway colonisation with <i>Pseudomonas aeruginosa</i> (PA) represents a hallmark of cystic fibrosis (CF). Mechanisms by which PA establishes pulmonary infection are undoubtedly complex and, in part, will reflect the capacity to interfere with host defense mechanisms. Dendritic cells (DCs) represent the most potent antigen-presenting cells in the lungs, with the unique ability to prime naïve T cells. PA-induced apoptosis has been demonstrated in epithelial cells and macrophages. We examined the capacity of PA to induce cell death in human dendritic cells, the cytotoxicity of clinical PA isolates, and the impact on antigen-presenting capacity. <h3>Methods</h3> CD14<sup>+</sup> monocytes were isolated from peripheral blood of healthy controls (n=11) and individuals with CF (n=5). Monocyte-derived DCs were generated by culture in the presence of IL-4 and GM-CSF. DCs were infected with live PA including isogenic laboratory strains of PA103 and PA isolates derived from the sputum of patients with CF. Heat-inactivated PA were utilised to evaluate the role of bacterial membrane components. Presence of early apoptosis and established cell death was analysed via annexin-V and 7-AAD incorporation, respectively. Cytotoxicity was further demonstrated via LDH release into the supernatant. Co-stimulatory molecules, CD40 and CD86, were measured via flow cytometry. <h3>Results</h3> PA readily induced apoptosis and cell death in human DCs, with cytotoxicity seen within 3 h of infection. Induction of apoptosis by PA was an active process requiring live organisms, but was not dependent on a functional type III secretion system. A significant decrease in viable DCs was seen in response to infection with clinical PA strains at 3 h and 20 h compared with laboratory PA103 strains (p&lt;0.05 and p&lt;0.001, respectively). Due to increased cytotoxicity of clinical PA isolates, post-infection DCs demonstrated no increase in co-stimulatory molecule expression compared with uninfected DCs (p&gt;0.05). <h3>Conclusions</h3> These data demonstrate that human dendritic cells are susceptible to apoptosis induced by <i>P aeruginosa</i>, with clinical isolates of PA demonstrating high levels of cytotoxicity, and a subsequent reduction in DC antigen-presenting capacity. Elimination of these important antigen-presenting cells could lead to impairment of immune responses and thus a factor in the establishment of chronic PA colonisation in the CF lung.
Quality of life in men with locally advanced prostate cancer treated with leuprorelin and radiotherapy with or without zoledronic acid (TROG 03.04 RADAR): secondary endpoints from a randomised phase 3 factorial trial
Authors: James W Denham, Chantelle Wilcox, David Joseph, Nigel A Spry, David S Lamb, Keen-Hun Tai, John Matthews, Chris Atkinson, Sandra Turner, David Christie, Nirdosh Kumar Gogna, Lizbeth Kenny, Gillian Duchesne, Brett Delahunt, Patrick McElduff
Journal: The Lancet Oncology (2012)
DNA Methyltransferase Inhibition Reverses Epigenetically Embedded Phenotypes in Lung Cancer Preferentially Affecting Polycomb Target Genes
Authors: Antje Hascher, Ann-Kristin Haase, Katja Hebestreit, Christian Rohde, Hans-Ulrich Klein, Maria Rius, Dominik Jungen, Anika Witten, Monika Stoll, Isabell Schulze, Seishi Ogawa, Rainer Wiewrodt, Lara Tickenbrock, Wolfgang E. Berdel, Martin Dugas, Nils H. Thoennissen, Carsten Müller-Tidow
Journal: Clinical Cancer Research (2013)

Cancer cell phenotypes are partially determined by epigenetic specifications, such as DNA methylation. Metastasis development is a late event in cancerogenesis and might be associated with epigenetic alterations.An in vivo selection approach was used to generate highly aggressive non-small cell lung cancer (NSCLC) cell lines (A549 and HTB56) followed by genome-wide DNA methylation analysis. Furthermore, the therapeutic effects of the epigenetic agent azacytidine on DNA methylation patterns and the in vivo phenotypes were explored.Widespread changes of DNA methylation were observed during development of highly aggressive cell lines. Up to 2.5% of the CpG-rich region was differentially methylated as identified by reduced representation bisulfite sequencing compared with the less aggressive parental cell lines. DNA methyltransferase inhibition by azacytidine reversed the prometastatic phenotype; this was highly associated with the preferential loss of DNA methylation at sites that were hypermethylated during the in vivo selection. Of note, polycomb (PRC2) binding sites were particularly affected by DNA methylation changes after azacytidine exposure that persisted over time.We could show that metastatic capability of NSCLC is closely associated with DNA methylome alterations. Because inhibition of DNA methyltransferase reversed metastasis-prone phenotype, epigenetic modulation seems to be a potential therapeutic approach to prevent metastasis formation.
Local and systemic glucocorticoid metabolism in inflammatory arthritis
Authors: R Hardy, E H Rabbitt, A Filer, P Emery, M Hewison, P M Stewart, N J Gittoes, C D Buckley, K Raza, M S Cooper
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Background:</h3> Isolated, primary synovial fibroblasts generate active glucocorticoids through expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). This enzyme produces cortisol from inactive cortisone (and prednisolone from prednisone). <h3>Objective:</h3> To determine how intact synovial tissue metabolises glucocorticoids and to identify the local and systemic consequences of this activity by examination of glucocorticoid metabolism in patients with rheumatoid arthritis (RA). <h3>Methods:</h3> Synovial tissue was taken from patients with RA during joint replacement surgery. Glucocorticoid metabolism in explants was assessed by thin-layer chromatography and specific enzyme inhibitors. RT-PCR and immunohistochemistry were used to determine expression and distribution of 11β-HSD enzymes. Systemic glucocorticoid metabolism was examined in patients with RA using gas chromatography/mass spectrometry. <h3>Results:</h3> Synovial tissue synthesised cortisol from cortisone, confirming functional 11β-HSD1 expression. In patients with RA, enzyme activity correlated with donor erythrocyte sedimentation rate (ESR). Synovial tissues could also convert cortisol back to cortisone. Inhibitor studies and immunohistochemistry suggested this was owing to 11β-HSD2 expression in synovial macrophages, whereas 11β-HSD1 expression occurred primarily in fibroblasts. Synovial fluids exhibited lower cortisone levels than matched serum samples, indicating net local steroid activation. Urinary analyses indicated high 11β-HSD1 activity in untreated patients with RA compared with controls and a significant correlation between total body 11β-HSD1 activity and ESR. <h3>Conclusions:</h3> Synovial tissue metabolises glucocorticoids, the predominant effect being glucocorticoid activation, and this increases with inflammation. Endogenous glucocorticoid production in the joint is likely to have an impact on local inflammation and bone integrity.
Serum uric acid as a predictor of mortality and future exacerbations of COPD
Authors: Konstantinos Bartziokas, Andriana I. Papaioannou, Stelios Loukides, Alexandros Papadopoulos, Aikaterini Haniotou, Spyridon Papiris, Konstantinos Kostikas
Journal: European Respiratory Journal (2013)

Serum uric acid is increased in respiratory disease, especially in the presence of hypoxia and systemic inflammation. We evaluated serum uric acid as a biomarker for prediction of mortality and future acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Serum uric acid was measured in 314 eligible consecutive patients on admission for AECOPD. Patients were evaluated monthly for 1 year. Uric acid levels were higher in patients with more severe airflow limitation and in those experiencing frequent exacerbations. High uric acid levels (≥6.9 mg·dL(-1)) were an independent predictor of 30-day mortality in multivariate Cox regression analysis (HR 1.317, 95% CI 1.011-1.736; p=0.044), but not of 1-year mortality. Patients with high serum uric acid required more prolonged hospitalisation, and more often needed noninvasive ventilation and admission to the intensive care unit within 30 days. In addition, high uric acid levels were associated with increased risk and hospitalisation for AECOPD in 1 year in multivariate Poisson regression analysis (incidence rate ratio 1.184 (95% CI 1.125-1.246) and 1.190 (95% CI 1.105-1.282), respectively; both p<0.001). Serum uric acid is associated with increased 30-day mortality and risk for AECOPD and hospitalisations in 1-year follow-up. This low-cost biomarker may be useful in the identification of high-risk chronic obstructive pulmonary disease patients that could benefit from intensive management.
Mitotic activity and acid hydrolase levels in human epidermis following a single dose of ultraviolet radiation
Authors: P.D. MIER, J.J.M.A. HURK, F.W. BAUER, R.M. GROOD, H. ROELFZEMA
Journal: British Journal of Dermatology (1977)

Journal Article Mitotic activity and acid hydrolase levels in human epidermis following a single dose of ultraviolet radiation Get access P.D. MIER, P.D. MIER Department of Dermatology, University of Nijmegen, Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar J.J.M.A. VAN DEN HURK, J.J.M.A. VAN DEN HURK Department of Dermatology, University of Nijmegen, Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar F.W. BAUER, F.W. BAUER Department of Dermatology, University of Nijmegen, Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar R.M. DE GROOD, R.M. DE GROOD Department of Dermatology, University of Nijmegen, Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar H. ROELFZEMA H. ROELFZEMA Department of Dermatology, University of Nijmegen, Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 96, Issue 2, 1 February 1977, Pages 163–165, https://doi.org/10.1111/j.1365-2133.1977.tb12538.x Published: 01 February 1977
Late-breaking abstract: IFN-gamma CA microsatellite polymorphism is associated with the susceptibility and severity to respiratory syncytial virus infection
Authors: Mingzhi Zhang, Jianfeng Huang, Libo Wang
Journal: European Respiratory Journal (2014)

Aim: To investigate the relationship between the polymorphism of CA microsatellite(rs3138557) in IFNgamma gene and theseverity to respiratory syncytial virus (RSV) infection.  Methods: The IFNgamma CA microsatellite was tested in 218 RSV bronchiolitis inpatients and 303 healthy children as control. The severity of RSV bronchiolitis was evaluated by standardized respiratory scoring system  Results: (1) The frequencies of CA12+/CA12+, CA12+/CA12- and CA12-/CA12- in the RSV bronchiolitis group were11%, 55.05% and35.95% respectively. The frequencies in the control group were19.47%, 52.81% and 27.72% respectively. The gene polymorphism of IFN gamma CA repeats between both groups was statistically different (P = 0.024).  (2) The clinical respiratory scores of RSV bronchiolitis cases with CA12+/CA12+, CA12+/CA12- were 2.84 plusmn 0.41; 2.95plusmn0.44 respectively. These scores were lower than those with CA12-/CA12- (3.10plusmn0.36).(P=0.004; P=0.027).  Conclusion: The polymorphism of IFN gamma CA microsatellite is associated with the susceptibility and severity of RSV infection in Chinese Han children.  Key words: IFNgamma , gene polymorphism, CA microsatellite , RSV bronchiolitis