tbuckley/cabot-search huggingface dataset:
Asthma–COPD Overlap. Clinical Relevance of Genomic Signatures of Type 2 Inflammation in Chronic Obstructive Pulmonary Disease
Authors: Stephanie A. Christenson, Katrina Steiling, Maarten van den Berge, Kahkeshan Hijazi, Pieter S. Hiemstra, Dirkje S. Postma, Marc E. Lenburg, Avrum Spira, Prescott G. Woodruff
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids.Objectives: To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features.Methods: We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89).Measurements and Main Results: The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting significant gene expression overlap. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD.Conclusions: These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and “asthma-like” features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma.
Adler's Psychology and Group Psychotherapy
Authors: HELENE PAPANEK
Journal: American Journal of Psychiatry (1970)

Adler's concept of the social nature of man favored the use of group treatment, as exemplified by the Child Guidance Clinics in Vienna. Adler considered social interest the criterion of mental health, and the interactions in group therapy foster the development of this social interest. The author deals with the growing use of group therapy, its bases in the principles of Individual Psychology, and the value of a social setting as the mode of treatment.
β2-adrenoceptor polymorphisms and asthma from childhood to middle age in the British 1958 birth cohort: a genetic association study
Authors: Ian P Hall, John D Blakey, Khalid A Al Balushi, Amanda Wheatley, Ian Sayers, Marcus E Pembrey, Susan M Ring, Wendy L McArdle, David P Strachan
Journal: The Lancet (2006)
TRANSAMINASES IN SKIN DISEASE.
Authors: A. TICKNER, P. D. MIER, M. P. McCABE
Journal: British Journal of Dermatology (1961)

Journal Article TRANSAMINASES IN SKIN DISEASE. Get access A. TICKNER, A. TICKNER Institute of Dermatology, St. John's Hospital for Diseases of the Skin, London, W.C.2 Search for other works by this author on: Oxford Academic Google Scholar P. D. MIER, P. D. MIER Institute of Dermatology, St. John's Hospital for Diseases of the Skin, London, W.C.2 Search for other works by this author on: Oxford Academic Google Scholar M. P. McCABE M. P. McCABE Institute of Dermatology, St. John's Hospital for Diseases of the Skin, London, W.C.2 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 73, Issue 5, 1 May 1961, Pages 180–184, https://doi.org/10.1111/j.1365-2133.1961.tb14429.x Published: 01 May 1961
Ethical Issues for Control-Arm Patients After Revelation of Benefits of Experimental Therapy: A Framework Modeled in Neuroblastoma
Authors: Yoram Unguru, Steven Joffe, Conrad V. Fernandez, Alice L. Yu
Journal: Journal of Clinical Oncology (2013)

In 2009, the Children's Oncology Group (COG) phase III randomized controlled trial, ANBL0032, found that adding immunotherapy (Ch14.18) to standard therapy significantly improved outcomes in patients with high-risk neuroblastoma when administered within 110 days after autologous stem-cell transplantation (SCT). After careful deliberation and consultation, the COG Neuroblastoma Committee decided to offer Ch14.18 to prior trial participants who had been randomly assigned to the control arm (no immunotherapy), regardless of the time that had elapsed since SCT. This decision occurred in the context of a limited supply of Ch14.18 and no data regarding its role when administered beyond 110 days. In this article, we analyze the numerous ethical challenges highlighted by the ANBL0032 trial, including the limits of researchers' reciprocity-based obligations to study participants, post-trial access to beneficial therapies, and the balance between scientific knowledge and parental hope. These deliberations may be useful to other researchers when considering their ethical obligations to control-arm participants in the wake of a positive randomized trial.
Replication of <i>Plasmodium</i> in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance
Authors: Jing-wen Lin, Roberta Spaccapelo, Evelin Schwarzer, Mohammed Sajid, Takeshi Annoura, Katrien Deroost, Raimond B.G. Ravelli, Elena Aime, Barbara Capuccini, Anna M. Mommaas-Kienhuis, Tom O’Toole, Frans Prins, Blandine M.D. Franke-Fayard, Jai Ramesar, Séverine Chevalley-Maurel, Hans Kroeze, Abraham J. Koster, Hans J. Tanke, Andrea Crisanti, Jean Langhorne, Paolo Arese, Philippe E. Van den Steen, Chris J. Janse, Shahid M. Khan
Journal: The Journal of Experimental Medicine (2015)

Most studies on malaria-parasite digestion of hemoglobin (Hb) have been performed using P. falciparum maintained in mature erythrocytes, in vitro. In this study, we examine Plasmodium Hb degradation in vivo in mice, using the parasite P. berghei, and show that it is possible to create mutant parasites lacking enzymes involved in the initial steps of Hb proteolysis. These mutants only complete development in reticulocytes and mature into both schizonts and gametocytes. Hb degradation is severely impaired and large amounts of undigested Hb remains in the reticulocyte cytoplasm and in vesicles in the parasite. The mutants produce little or no hemozoin (Hz), the detoxification by-product of Hb degradation. Further, they are resistant to chloroquine, an antimalarial drug that interferes with Hz formation, but their sensitivity to artesunate, also thought to be dependent on Hb degradation, is retained. Survival in reticulocytes with reduced or absent Hb digestion may imply a novel mechanism of drug resistance. These findings have implications for drug development against human-malaria parasites, such as P. vivax and P. ovale, which develop inside reticulocytes.
Pathogenesis of ANCA-associated vasculitides
Authors: C. G. M. Kallenberg
Journal: Annals of the Rheumatic Diseases (2011)

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides are characterised by necrotising inflammation of small vessels in conjunction with ANCA directed to either proteinase 3 (PR3) or myeloperoxidase (MPO). The aetiopathogenesis of these disorders is still not fully elucidated but clinical as well as in vitro and in vivo experimental data strongly suggest a role for the autoimmune responses to PR3 and MPO in disease development. Clinically, PR3-ANCA are strongly associated with granulomatous vasculitis as in Wegener9s granulomatosis, and MPO-ANCA with necrotising small vessel vasculitis as in microscopic polyangiitis. Levels of PR3-ANCA and MPO-ANCA do, however, not fully reflect disease activity. In vitro, ANCA activate primed neutrophils to release lytic enzymes and reactive oxygen species, a process reinforced by the alternative pathway of complement. In the context of endothelial cells, this process leads to endothelial detachment and lysis. In vivo experimental studies have clearly demonstrated the pathogenic potential of MPO-ANCA for necrotising glomerulonephritis and pulmonary capillaritis. For PR3-ANCA-associated granulomatous vasculitis, an animal model is lacking. Here, effector T cells, in particular Th17 cells, appear to have a major pathogenic role in addition to ANCA. Finally, microbial factors, derived in particular from S aureus and Gram-negative bacteria, could play a part in disease induction and expression. These new insights into the pathogenesis of ANCA-associated vasculitides have opened new ways for targeted treatment.
Overexpression of Interleukin-10 by Activated T Lymphocytes Inhibits Atherosclerosis in LDL Receptor–Deficient Mice by Altering Lymphocyte and Macrophage Phenotypes
Authors: Laura J. Pinderski, Michael P. Fischbein, Ganesamoorthy Subbanagounder, Michael C. Fishbein, Nobuhiko Kubo, Hilde Cheroutre, Linda K. Curtiss, Judith A. Berliner, William A. Boisvert
Journal: Circulation Research (2002)

Previous studies demonstrated that interleukin-10 (IL-10) overexpression decreases formation of early fatty-streak lesions in mice independent of lipoprotein levels. The present studies, using bone marrow transplantation, demonstrate that overexpression of IL-10 by T cells inhibits advanced atherosclerotic lesions in LDL receptor–null mice fed an atherogenic diet. In mice receiving bone marrow from the IL-10 transgenic mice compared with those receiving wild-type marrow, there was a 47% decrease in lesion size and a marked decrease in lesion complexity with an 80% reduction in the necrotic core. Accumulation of cholesterol and phospholipid oxidation products in the aorta was decreased by 50% to 80%, unrelated to plasma lipid or IL-10 levels. Our studies also provide insight into the mechanism of the IL-10–mediated decrease in lesion size. Although a strong influence toward a Th1 phenotype has previously been demonstrated in atherosclerotic models, T lymphocytes in the IL-10 transgenic (Tg) group revealed a marked shift to a Th2 phenotype, with decreased IFN-γ production and an increase in IL-10. Evaluation of specific immunoglobulin subclasses demonstrated a preponderance of IgG 1 isotype, characteristic of a Th2 influence on B cell immunoglobulin class-switching in the IL-10 Tg group. A major finding of these studies was altered monocyte/macrophage function in the IL-10 Tg group. Monocytes showed a decrease in activation resulting in decreased expression of IFN-γ. Furthermore, macrophage foam cells within lesions of the IL-10 Tg group exhibited markedly decreased apoptosis. These studies demonstrate that T lymphocyte IL-10 can influence the function of other immune cells to reduce the development of advanced atherosclerotic lesions in mice.
Exposure to volatile organic compounds and loss of pulmonary function in the elderly
Authors: H.I. Yoon, Y-C. Hong, S-H. Cho, H. Kim, Y.H. Kim, J.R. Sohn, M. Kwon, S-H. Park, M-H. Cho, H-K. Cheong
Journal: European Respiratory Journal (2010)

Volatile organic compounds (VOCs) are reported to cause adverse effects on pulmonary function in occupationally exposed workers. However, evidence is lacking on the effect in the general population. We hypothesised that VOCs impair pulmonary function through enhancing oxidative stress, especially in the elderly population. A longitudinal panel study of 154 elderly people was performed in South Korea. Repeated spirometric tests were performed up to eight times on different days for each subject. We also measured urinary concentrations of metabolites of the VOC and markers of oxidative stress (malondialdehyde and 8-oxo-2′-deoxyguanosine) on the same day of spirometric tests. A mixed linear regression model was used to evaluate the association among the VOC metabolites, oxidative stress markers and spirometric tests. We found that the urinary levels of hippuric acid and methylhippuric acid, which are metabolites of toluene and xylene, respectively, were significantly associated with reduction of forced expiratory volume in 1 s (FEV 1 ), FEV 1 /forced vital capacity (FVC), and forced expiratory flow at 25–75% of FVC. We also found significant associations between the metabolites of VOCs and the markers of oxidative stress. In addition, the oxidative stress markers were associated with pulmonary function parameters. This study suggests that exposure to toluene and xylene exert a harmful effect on pulmonary function by exacerbating oxidative stress in elderly people.
Subjective differentiation of normal and pathological bronchi on thin-section CT: impact of observer training
Authors: A.A. Bankier, D. Fleischmann, V. De Maertelaer, M. Kontrus, T. Zontsich, K. Hittmair, R. Mallek
Journal: European Respiratory Journal (1999)

The effect of observer training on sensitivity, specificity and interobserver agreement in the differentiation between normal and pathological bronchi on computed tomography (CT) was studied. The wall thickness of bronchi with normal walls and with pathologically thickened walls were subjectively scored by three independent observers before and after a training period of 2 weeks. Sensitivity, specificity and interobserver agreement were calculated for reading sessions before and after training. Increase and decrease in agreement after training were determined. There was a statistically significant difference (p=0.001) between objectively measured wall thickness of normal and pathological bronchi, both for reference bronchi and for bronchi used for reading sessions. While training increased interobserver agreement, it had no effect on sensitivity (0.46 versus 0.44 after training) and specificity (0.71 versus 0.72 after training) in detecting pathological bronchi. Increased agreement after training was significantly (p=0.001) more frequent than decreased agreement. There is a discrepancy between the effect of training on interobserver agreement and on sensitivity and specificity in the subjective differentiation between normal and pathological bronchi. Interobserver agreement alone is not a reliable indicator of a beneficial effect of training in the evaluation of this parameter.
Ryanodine Receptor Phosphorylation by Calcium/Calmodulin-Dependent Protein Kinase II Promotes Life-Threatening Ventricular Arrhythmias in Mice With Heart Failure
Authors: Ralph J. van Oort, Mark D. McCauley, Sayali S. Dixit, Laetitia Pereira, Yi Yang, Jonathan L. Respress, Qiongling Wang, Angela C. De Almeida, Darlene G. Skapura, Mark E. Anderson, Donald M. Bers, Xander H.T. Wehrens
Journal: Circulation (2010)

approximately half of patients with heart failure die suddenly as a result of ventricular arrhythmias. Although abnormal Ca(2+) release from the sarcoplasmic reticulum through ryanodine receptors (RyR2) has been linked to arrhythmogenesis, the molecular mechanisms triggering release of arrhythmogenic Ca(2+) remain unknown. We tested the hypothesis that increased RyR2 phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II is both necessary and sufficient to promote lethal ventricular arrhythmias.mice in which the S2814 Ca(2+)/calmodulin-dependent protein kinase II site on RyR2 is constitutively activated (S2814D) develop pathological sarcoplasmic reticulum Ca(2+) release events, resulting in reduced sarcoplasmic reticulum Ca(2+) load on confocal microscopy. These Ca(2+) release events are associated with increased RyR2 open probability in lipid bilayer preparations. At baseline, young S2814D mice have structurally and functionally normal hearts without arrhythmias; however, they develop sustained ventricular tachycardia and sudden cardiac death on catecholaminergic provocation by caffeine/epinephrine or programmed electric stimulation. Young S2814D mice have a significant predisposition to sudden arrhythmogenic death after transverse aortic constriction surgery. Finally, genetic ablation of the Ca(2+)/calmodulin-dependent protein kinase II site on RyR2 (S2814A) protects mutant mice from pacing-induced arrhythmias versus wild-type mice after transverse aortic constriction surgery.our results suggest that Ca(2+)/calmodulin-dependent protein kinase II phosphorylation of RyR2 Ca(2+) release channels at S2814 plays an important role in arrhythmogenesis and sudden cardiac death in mice with heart failure.
Religiousness and Spiritual Support Among Advanced Cancer Patients and Associations With End-of-Life Treatment Preferences and Quality of Life
Authors: Tracy A. Balboni, Lauren C. Vanderwerker, Susan D. Block, M. Elizabeth Paulk, Christopher S. Lathan, John R. Peteet, Holly G. Prigerson
Journal: Journal of Clinical Oncology (2007)

Religion and spirituality play a role in coping with illness for many cancer patients. This study examined religiousness and spiritual support in advanced cancer patients of diverse racial/ethnic backgrounds and associations with quality of life (QOL), treatment preferences, and advance care planning.The Coping With Cancer study is a federally funded, multi-institutional investigation examining factors associated with advanced cancer patient and caregiver well-being. Patients with an advanced cancer diagnosis and failure of first-line chemotherapy were interviewed at baseline regarding religiousness, spiritual support, QOL, treatment preferences, and advance care planning.Most (88%) of the study population (N = 230) considered religion to be at least somewhat important. Nearly half (47%) reported that their spiritual needs were minimally or not at all supported by a religious community, and 72% reported that their spiritual needs were supported minimally or not at all by the medical system. Spiritual support by religious communities or the medical system was significantly associated with patient QOL (P = .0003). Religiousness was significantly associated with wanting all measures to extend life (odds ratio, 1.96; 95% CI, 1.08 to 3.57).Many advanced cancer patients' spiritual needs are not supported by religious communities or the medical system, and spiritual support is associated with better QOL. Religious individuals more frequently want aggressive measures to extend life.
The Rho Kinases: Critical Mediators of Multiple Profibrotic Processes and Rational Targets for New Therapies for Pulmonary Fibrosis
Authors: Rachel S. Knipe, Andrew M. Tager, James K. Liao
Journal: Pharmacological Reviews (2014)

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung scarring, short median survival, and limited therapeutic options, creating great need for new pharmacologic therapies. IPF is thought to result from repetitive environmental injury to the lung epithelium, in the context of aberrant host wound healing responses. Tissue responses to injury fundamentally involve reorganization of the actin cytoskeleton of participating cells, including epithelial cells, fibroblasts, endothelial cells, and macrophages. Actin filament assembly and actomyosin contraction are directed by the Rho-associated coiled-coil forming protein kinase (ROCK) family of serine/threonine kinases (ROCK1 and ROCK2). As would therefore be expected, lung ROCK activation has been demonstrated in humans with IPF and in animal models of this disease. ROCK inhibitors can prevent fibrosis in these models, and more importantly, induce the regression of already established fibrosis. Here we review ROCK structure and function, upstream activators and downstream targets of ROCKs in pulmonary fibrosis, contributions of ROCKs to profibrotic cellular responses to lung injury, ROCK inhibitors and their efficacy in animal models of pulmonary fibrosis, and potential toxicities of ROCK inhibitors in humans, as well as involvement of ROCKs in fibrosis in other organs. As we discuss, ROCK activation is required for multiple profibrotic responses, in the lung and multiple other organs, suggesting ROCK participation in fundamental pathways that contribute to the pathogenesis of a broad array of fibrotic diseases. Multiple lines of evidence therefore indicate that ROCK inhibition has great potential to be a powerful therapeutic tool in the treatment of fibrosis, both in the lung and beyond.
Outcomes of hospitalisation for right heart failure in pulmonary arterial hypertension
Authors: A. Campo, S.C. Mathai, J. Le Pavec, A.L. Zaiman, L.K. Hummers, D. Boyce, T. Housten, N. Lechtzin, H. Chami, R.E. Girgis, P.M. Hassoun
Journal: European Respiratory Journal (2011)

The aim of this study was to examine the causes and outcomes of hospitalisation in patients with pulmonary arterial hypertension (PAH). 205 consecutive hospitalisations occurring between 2000 and 2009 in 90 PAH patients were studied. The leading causes for hospitalisation were right heart failure (RHF; 56%), infection (16%) and bleeding disorders (8%). For patients with RHF, in-hospital mortality was 14% overall, 46% for patients receiving inotropes and 48% for those admitted to the intensive care unit. The predictors for in-hospital mortality were the presence of connective tissue disease (CTD) (OR 4.92), systolic blood pressure &lt;100 mmHg (OR 4.32) and Na ≤136 mEq·L −1 (OR 4.29). Mortality after discharge was 13, 26 and 35% at 3, 6 and 12 months, respectively. World Health Organization functional class prior to admission, renal dysfunction, Charlson comorbidity index, and the presence of CTD were all predictors of mortality after discharge. Hyponatraemia and low systolic blood pressure upon admission and underlying CTD are the main prognostic factors for in-hospital mortality in patients with PAH admitted for RHF. The short-term outcomes after discharge are poor and remarkably worse in patients with underlying CTD or renal impairment. Early recognition of these factors may guide decisions regarding more aggressive therapy, including consideration for lung transplantation.
Measurement of coronary collateral flow and resistance in the presence of an open critical stenosis, and the response to intra-arterial thrombosis
Authors: M Mansaray
Journal: Cardiovascular Research (2000)

(1) Can one measure coronary collateral flow around an open critical stenosis? (2) Does intracoronary platelet thrombosis affect native coronary collateral vessels?We measured regional myocardial blood flow by the radioactive microsphere technique in seven anaesthetised dogs with an ultrasonic flowmeter on the circumflex branch of the left coronary artery (LCx). Measurements were made (a) in a control period, (b) after induction of a tight stenosis on the LCx, and (c) after additional arterial damage at the stenosis to induce intraluminal thrombosis. Collateral flow was calculated from LCx tissue flow(in ml/min/g tissue) minus LCx flowmeter flow which is in ml/min. Therefore, it was necessary to use scaling by reference back to the control measurements and conversion to ml/min/g tissue equivalent.LCx stenosis induced collateral flow from the other coronary arteries into the LCx area of supply, which decreased (mean+/-S.E.) from 0.23+/-0.03 to 0.15+/-0.05 ml/min/g tissue with thrombosis. Collateral resistance correspondingly increased with thrombosis from 187.6+/-18. 2 to 1069+/-544 mmHg/ml/min/g (P<0.02).Coronary collateral flow around an open stenosis can be measured by reference back to control conditions. The coronary collaterals vasoconstrict in the presence of thrombosis even though they are in the stream of blood coming from normal coronary arteries.