tbuckley/cabot-search huggingface dataset:
Tiotropium reduces established pulmonary inflammation in a 12 weeks cigarette smoke mouse model of COPD
Authors: Lutz Wollin, Florian Gantner, Michael Pieper
Journal: European Respiratory Journal (2011)

Rationale:  Tiotropium bromide (Spiriva®) is the only marketed long acting anticholinergic for the treatment of chronic obstructive pulmonary disease (COPD). We recently demonstrated that tiotropium reduces established cigarette smoke (CS)-induced lung inflammation in a short term mouse model.   Aim:  To investigate the therapeutic anti-inflammatory activity of tiotropium on CS-induced lung inflammation in a chronic 12 weeks mouse model.   Methods:  All mice except controls were exposed to CS for 3 weeks (W) to elicit pronounced lung inflammation. Thereafter, 4 groups of mice were either further exposed to CS or room air (RA) with or without tiotropium treatment up to W12. Tiotropium was administered by inhalation (0.1 mg/mL for 5 min) 1 h prior to CS or RA exposure. Cell counts in the bronchoalveolar lavage (BAL) were determined at W3, W8, and W12.   Results:  Lung inflammation induced by 3 W of CS exposure was resolved 5 W after termination of smoke exposure regardless of Tiotropium treatment. Continued CS exposure increases lung inflammation to a maximum at W8. Tiotropium treatment of existing inflammation for 5 W completely inhibited the increase in neutrophil number and reduced monocytic inflammation. After 9 W of Tiotropium treatment the number of monocytes was reduced to baseline levels of healthy animals. Neutrophil number was significantly reduced by 58% after 9 W of Tiotropium treatment compared to sham treated CS exposed mice.   Conclusion:  The therapeutic anti-inflammatory properties of tiotropium bromide may contribute to the beneficial influence of tiotropium in chronic inflammatory airway diseases like COPD.
Novel antiviral properties of vitamin D in cystic fibrosis airway epithelial cells
Authors: Aline Schoegler, Brigitte S. Kopf, Ricardo J. Muster, Carmen Casaulta, Andreas Jung, Alexander Moeller, Thomas Geiser, Marco P. Alves, Nicolas Regamey
Journal: European Respiratory Journal (2014)

Introduction. CF patients suffer from pulmonary exacerbations induced by virus infections, most frequently triggered by rhinoviruses (RVs). Vitamin D deficiency is a widespread feature of CF patients. Recent evidences suggest that Vitamin D has important immunomodulatory activities in the defense towards pathogens. We hypothesize that Vitamin D has antiviral properties in primary CF airway epithelial cells.  Methods. Primary bronchial epithelial cells (BECs) from CF children were pretreated with different concentrations of Vitamin D (10-8 to 10-6 M) and infected with the major group virus RV16. Viral RNA and RV16 surface receptor intercellular adhesion molecule-1 (ICAM-1), pattern recognition receptors (PRRs) involved in detection of RV16, interferon (IFN)-λ2/3, viperin and the antimicrobial peptides cathelicidin and β-defensin expression was assessed by RT-qPCR. Levels of pro-inflammatory cytokines were determined by ELISA. Cell death was measured by Flow cytometry.  Results. Vitamin D reduced RV16 load in a dose-dependent manner in CF BECs (10-6M: p  Conclusion. Vitamin D lowers RV16 replication in primary paediatric CF BECs possibly through the induction of the antimicrobial peptide cathelicidin. Our in vitro study may point to the importance of an adequate control of the Vitamin D status in CF patients to prevent virus-induced exacerbations.
Metronomic oral chemotherapy (CT) versus the same regimen in association with Thalidomide (TLM): results of a randomized trial in patients (pts) with advanced breast cancer (ABC)
Authors: L. Orlando, M. Colleoni, F. Bertolini, R. Ghisini, G. Sanna, V. Formica, F. Nolè, G. Viale, L. Franceschelli, A. Goldhirsch
Journal: Journal of Clinical Oncology (2004)

3015 Background: Clinical efficacy and antiangiogenic effect of low dose, continuous oral cyclophosphamide (CTX) and methotrexate (MTX) have been demonstrated. We hypothesized that the addition of TLM might further improve clinical response and modulate angiogenic factors in pts with ABC. Methods: Pts with ABC, either untreated or pretreated, were randomized to receive an oral schedule of MTX (2.5 mg orally, twice daily on day 1 and day 4) and CTX (50 mg, orally, daily) (arm A) or to receive the same regimen plus TLM (200mg, orally, daily) (arm B). Blood samples were collected at first visit and monthly to measure VEGF, bFGF, and circulating endothelial cells. Results: 178 pts were enrolled, 166 were evaluable for response. PS was 0 (150 patients), 1 (28 patients). Metastatic sites: lung (40 pts), liver (75 pts), bone (79 pts), lymph nodes (48 pts), and skin (20 pts). Median age was 54 (range 31–78). Progressive disease at study entry reported in 113 pts. Pts were stratified by preatreatment (no = 58; yes = 120). In the latter, 75 pts were pretreated with 1 line of CT, 45 pts with ≥ 2. Three CR in arm A and 4 in arm B, 17 PR in arm A and 9 in arm B for an overall response of 24% in arm A e 16% in arm B, SD was seen in 29 pts in arm A and 31 in arm B. The overall clinical benefit (CR+ PR+ SD >24 weeks) was 47% for both arms. PD was observed in 41% of pts in arm A and in 47% of pts in arm B. Overall clinical toxicity was generally mild. Grade ≥2 leucopenia was reported in 39 pts. Grade ≥2 thrombocytopenia appeared in 4 pts. Grade ≥2 liver toxicity was reported in 59 pts. No difference in terms of toxicity were observed between the 2 arms, with exception of more neurological toxicity (grade ≥2) and higher incidence of thromboembolic events in the TLM arm. In arm B twelve pts (14%) stopped TLM: 8 due to neurological toxicity grade 1–2, 2 due to hematological toxicity, 2 due to skin toxicity. Two pts in Arm B had a Grade 4 pancytopenia (1) and thromboembolism (1). Conclusions: Adding TLM to continuous, low-dose CTX and MTX did not increase clinical responses in pts with ABC. No significant financial relationships to disclose.
Abstract 16772: Discovery of a Novel Approach for Modulating Angiogenesis: The Interaction Between Heat Shock Protein 27 and ATP5A1 Promotes Endothelial Cell Dynamics
Authors: Yumei Li, Chunhua Shi, Yongxiang Chen, Geremy Koumbadinga, Ayinuer Adijiang, Edward R O’Brien
Journal: Circulation (2014)

Introduction: ATP5A1 is the alpha subunit of the soluble F1 catalytic core of mitochondrial ATP synthase that catalyzes ATP synthesis. Previous studies identified ATP synthase as the receptor for the anti-angiogenic factor, angiostatin. We demonstrated that Heat Shock Protein 27 (HSP27) functions in the extracellular space to accelerate re-endothelialization (FASEB 2014) and more recently using mass spectrometry identified ATP5A1 as a potential cell membrane client protein of HSP27. Hypothesis: HSP27 interacts with ATP5A1 to promote endothelial dynamics. Methods / Results: (1) The binding of HSP27 to ATP5A1 was quantified using an ELISA by coating plates with an anti-ATP5A1 antibody. While a negative control truncated C-terminus form of HSP27 did not bind ATP5A1, full length HSP27 showed an abundant binding pattern to HSP27 that was further enhanced by the presence of auto-antibodies to HSP27. (2) As detected by immunofluorescence imaging and use of a fluorescent activated cell sorter, ATP5A1 expression was up-regulated in endothelial cells that over-express HSP27. (3) ATP production in endothelial cells was increased after exposure to HSP27 (p&lt;0.01 vs. control; detected using a Luciferin-Luciferase ATP detection assay). (4) Endothelial cell migration in vitro was increased with the addition of HSP27. Indeed, HSP27 in combination with anti-HSP27 auto-antibodies potentiated the interaction with ATP5A1. Conclusions: The interaction of HSP27 with cell membrane localized ATP5A1 appears to be a key mechanism of enhancing endothelial cell dynamics. Interestingly, the presence of auto-antibodies to HSP27 potentiates this effect and is explained in separately described data regarding anti-HSP27 immune phenomena in cell signaling. These data provide for the first time impetus for the development of angiogenesis modulating strategies that either promote or antagonize the interaction between HSP27 and ATP5A1 in order to enhance or suppress angiogenesis, respectively.
Novel targets for interleukin 18 binding protein
Authors: C A Dinarello
Journal: Annals of the Rheumatic Diseases (2001)

Interleukin 18 (IL18) is related to the IL1 family by structure, receptors, signalling molecules, and function. IL18 induces gene expression and synthesis of tumour necrosis factor (TNF), IL1, Fas ligand, several chemokines, and vascular adhesion molecules. Similar to IL1beta, IL18 is synthesised as a biologically inactive precursor molecule lacking a signal peptide. The IL18 precursor requires cleavage into an active, mature molecule by the intracellular cysteine protease, IL1beta converting enzyme (ICE, or caspase-1). Inhibitors of ICE activity limit the biological activity of IL18 in animals and may be useful in reducing the activity of IL18 in human disease. However, a constitutively secreted IL18 binding protein (IL18BP) exists which functions as a natural inhibitor of IL18 activity. IL18BP binds IL18 with a high affinity (Kd of 400 pM) and, at equimolar ratios, inhibits 50-70% of IL18; at twofold molar excess, IL18BP neutralises nearly all IL18 activity.IL18 was investigated for its role in human myocardial function. An ischaemia/reperfusion (I/R) model of suprafused human atrial myocardium was used to assess myocardial contractile force.The addition of IL18BP to the perfusate during and after I/R resulted in improved post-I/R contractile function from 35% of control to 76% with IL18BP. Also, IL18BP treatment preserved intracellular tissue creatine kinase levels (by 420%). Because active IL18 requires cleavage of its precursor form by ICE, inhibition of ICE attenuated the depression in contractile force after I/R (from 35% of control compared with 75.8% in treated atrial muscle, p<0.01).Myocardial ischaemia is a target for IL18BP and use of IL18BP may thereby reduce ischaemia-induced myocardial dysfunction.
A Cost-Effectiveness Analysis of Erythropoiesis-Stimulating Agents for Treating Cancer-Treatment Induced Anaemia
Authors: N. Huxley, T. Snowsill, M. Hoyle, L. Crathorne, M. Haasova, S. Briscoe, H. Coelho, A. Medina-Lara, R. Mujica-Mota, M. Napier, C. Hyde
Journal: Annals of Oncology (2014)
PTPN22 Variant R620W Is Associated With Reduced Toll-like Receptor 7-Induced Type I Interferon in Systemic Lupus Erythematosus
Authors: Yaya Wang, David Ewart, Juliet N. Crabtree, Ami Yamamoto, Emily C. Baechler, Parastoo Fazeli, Erik J. Peterson
Journal: Arthritis & Rheumatology (2015)

Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is associated with an increased risk of systemic lupus erythematosus (SLE). PTPN22 encodes Lyp, and a disease-associated coding variant bears an R620W substitution (LypW). LypW carriage is associated with impaired production of type I interferon (IFN) by myeloid cells following Toll-like receptor (TLR) engagement. The aim of this study was to investigate the effects of LypW carriage on TLR signaling in patients with SLE.Plasma IFNα concentrations and whole-blood IFN gene scores were compared in SLE patients who were LypW carriers and those who were noncarriers. TLR-7 agonist R848-stimulated IFNα and tumor necrosis factor levels, IFN-dependent gene expression, and STAT-1 activation were determined in peripheral blood mononuclear cells (PBMCs) and/or plasmacytoid dendritic cells (PDCs) obtained from these patients. The effect of LypW expression on the systemic type I IFN response to R848 stimulation in vivo was assessed in transgenic mice.Plasma IFNα levels and whole-blood IFN gene signatures were comparable in SLE patients who were LypW carriers and those who were noncarriers. However, PBMCs from LypW carriers produced less IFNα and showed reduced IFN-dependent gene up-regulation and STAT-1 activation after R848 stimulation. The frequency of PDCs producing IFNα2 and the per-cell IFNα2 levels were significantly reduced in LypW carriers. LypW-transgenic mice displayed reduced TLR-7-induced circulating type I IFN responses.PDCs from SLE patients carrying the disease-associated PTPN22 variant LypW showed a reduced capacity for TLR-7 agonist-induced type I IFN production, even though LypW carriers displayed systemic type I IFN activation comparable with that observed in noncarriers. LypW carriage identifies SLE patients who may harbor defects in TLR- and PDC-dependent host defense or antiinflammatory functions.
Predictors of SpO2 ≤ 95% in a cross-sectional population based survey
Authors: Monica Linea Vold, Hasse Melbye, Ulf Aasebø
Journal: European Respiratory Journal (2011)

Background:  Pulse oximetry has become an important tool in evaluating, and monitoring pulmonary diseases. There is limited knowledge on distribution of SpO 2  values in a general population.   Aims and objectives:  We wanted to determine independent predictors of low pulse oximetry values in a screened population.   Methods:  A cross-sectional population based survey was performed in the city of Tromso, Norway, in 2007-2008. Valid spirometry and pulse oximetry (SpO 2 ) were performed in 6320 participants aged 38-87 years (57% women). The examinations also included questionnaires and readings for hemoglobin, C-reactive protein (CRP), pulse, weight and height. We considered resting oxygen saturation ≤ 95 as an abnormal value. Predictors of SpO 2  ≤ 95% with a statistical significance of p   Results:  We found SpO 2  ≤ 95% in 400 participants (6.3%) and SpO 2  ≤ 92 in 30 (0.5%). The strongest predictors in the logistic regression (p   Conclusion:  Independent predictors of SpO 2  ≤ 95% in this population based survey were BMI (↑), FEV1% predicted (↓), age (↑), hemoglobin (↑), CRP (↑), and history of smoking (↑).
Effect of Pregnancy on Overall Survival After the Diagnosis of Early-Stage Breast Cancer
Authors: Shari Gelber, Alan S. Coates, Aron Goldhirsch, Monica Castiglione-Gertsch, Gianluigi Marini, Jurij Lindtner, David Z. Edelmann, Anne Gudgeon, Vernon Harvey, Richard D. Gelber
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate the impact of subsequent pregnancy on the prognosis of patients with early breast cancer. PATIENTS AND METHODS: One hundred eight patients who became pregnant after diagnosis of early-stage breast cancer were identified in institutions participating in International Breast Cancer Study Group (IBCSG) studies. Fourteen had relapse of breast cancer before their first subsequent pregnancy. The remaining 94 patients (including eight who relapsed during pregnancy) formed the study group reported here. A comparison group of 188 was obtained by randomly selecting two patients, matched for nodal status, tumor size, age, and year of diagnosis from the IBCSG database, who were free of relapse for at least as long as the time between breast cancer diagnosis and completion of pregnancy for each pregnant patient. Survival comparison used Cox proportional hazards regression models. RESULTS: Overall 5- and 10-year survival percentages (± SE) measured from the diagnosis of early-stage breast cancer among the 94 study group patients were 92% ± 3% and 86% ± 4%, respectively. For the matched comparison group survival was 85% ± 3% at 5 years and 74% ± 4% at 10 years (risk ratio, 0.44; 95% confidence interval, 0.21 to 0.96; P = .04). CONCLUSION: Subsequent pregnancy does not adversely affect the prognosis of early-stage breast cancer. The superior survival seen in this and other controlled series may merely reflect a healthy patient selection bias, but is also consistent with an antitumor effect of the pregnancy.
A biopsychosocial approach to treating patients with affective disorders
Authors: R G Vasile, J A Samson, J Bemporad, K L Bloomingdale, D Creasey, B T Fenton, J E Gudeman, J J Schildkraut
Journal: American Journal of Psychiatry (1987)

The authors describe the development of an affective disorders consultation service that implemented a biopsychosocial model of subspecialty consultation within a university-affiliated community mental health center. They retrospectively analyzed the first 2 years of consultations, assessing the process of consultation and examining patterns of consultee inquiries and consultation recommendations. Consultants recommended combined psychopharmacologic and psychodynamic therapies for most patients and found psychodynamic psychotherapy strikingly overlooked by consultees, all of whom were psychiatrists or other mental health professionals. This evaluation documents the psychiatric consultees' deemphasis of the biopsychosocial perspective in clinical practice.
Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas
Authors: Bruce D. Cheson, Sandra J. Horning, Bertr Coiffier, Margaret A. Shipp, Richard I. Fisher, Joseph M. Connors, T. Andrew Lister, Julie Vose, Antonio Grillo-López, Anton Hagenbeek, Fernando Cabanillas, Donald Klippensten, Wolfgang Hiddemann, Ronald Castellino, Nancy L. Harris, James O. Armitage, William Carter, Richard Hoppe, George P. Canellos
Journal: Journal of Clinical Oncology (1999)

ABSTRACT: Standardized guidelines for response assessment are needed to ensure comparability among clinical trials in non-Hodgkin's lymphomas (NHL). To achieve this, two meetings were convened among United States and international lymphoma experts representing medical hematology/oncology, radiology, radiation oncology, and pathology to review currently used response definitions and to develop a uniform set of criteria for assessing response in clinical trials. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients—especially those with large-cell NHL—who may not have residual disease. Single-photon emission computed tomography gallium scans are encouraged as a valuable adjunct to assessment of patients with large-cell NHL, but such scans require appropriate expertise. Flow cytometric, cytogenetic, and molecular studies are not currently included in response definitions. Response rates may be the most important objective in phase II trials where the activity of a new agent is important and may provide support for approval by regulatory agencies. However, the goals of most phase III trials are to identify therapies that will prolong the progression-free survival, if not the overall survival, of the treated patients. We hope that these guidelines will serve to improve communication among investigators and comparability among clinical trials until clinically relevant laboratory and imaging studies are identified and become more widely available.
Augmentation of Tumor Immunity Against Syngeneic Tumors in Mice by β-Carotene<xref ref-type="fn" rid="FN2">2</xref>
Authors: Y Tomita, K Himeno, K Nomoto, H Endo, T Hirohata
Journal: JNCI Journal of the National Cancer Institute (1987)

The effect of beta-carotene on tumor immunity was examined with the use of a syngeneic murine tumor system. Oral administration of beta-carotene (120 micrograms/mouse/day) for 9 days from day 1 to the BALB/c mice inoculated sc with 10(7) syngeneic BALB/c Meth A fibrosarcoma cells (Meth A) led to a remarkable rejection against rechallenged Meth A implanted sc on day 10. The growth of Meth 1 fibrosarcoma (Meth 1), another syngeneic tumor of BALB/c origin, as a rechallenge tumor was unaffected by treatment with beta-carotene, thereby suggesting that beta-carotene may augment tumor rejection specific to tumor-specific antigens. Winn assay revealed that the suppressive effect on tumor growth of immune lymph node cells obtained from Meth A-inoculated beta-carotene-treated mice on day 12 was enhanced dose dependently. Primary effector cells responsible for the augmented rejection are Thy-1-positive, Lyt-1-negative, and Lyt-2-positive lymphocytes, presumably cytotoxic T-lymphocytes.
Shell Cleavable Dendritic Polyglycerol Sulfates Show High Anti‐Inflammatory Properties by Inhibiting L‐Selectin Binding and Complement Activation
Authors: Sabine Reimann, Dominic Gröger, Christian Kühne, Sebastian B. Riese, Jens Dernedde, Rainer Haag
Journal: Advanced Healthcare Materials (2015)

A new class of fully synthetic shell cleavable multivalent polysulfates is prepared by introducing degradable linkers into a stable biocompatible dendritic polyglycerol scaffold and subsequent sulfation. The sulfated polymers show different degradation profiles, low anticoagulant and high anti-inflammatory properties, are able to efficiently bind to L-selectin and inhibit the complement activation at very low concentrations in vitro.
Comparison of immunological parameters in patients with pemphigus vulgaris following rituximab and IVIG therapy
Authors: R.J. Feldman, W.G. Christen, A.R. Ahmed
Journal: British Journal of Dermatology (2011)

Journal Article Comparison of immunological parameters in patients with pemphigus vulgaris following rituximab and IVIG therapy Get access R.J. Feldman, R.J. Feldman Center for Blistering Diseases, 70 Parker Hill Ave, Suite 208, Boston, MA 02120, U.S.A Search for other works by this author on: Oxford Academic Google Scholar W.G. Christen, W.G. Christen Harvard School of Public Health, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, U.S.A Search for other works by this author on: Oxford Academic Google Scholar A.R. Ahmed A.R. Ahmed Center for Blistering Diseases, 70 Parker Hill Ave, Suite 208, Boston, MA 02120, U.S.A Razzaque Ahmed. E‐mail: arahmedmd@msn.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 166, Issue 3, 1 March 2012, Pages 511–517, https://doi.org/10.1111/j.1365-2133.2011.10658.x Published: 01 March 2012 Article history Accepted: 21 September 2011 Published: 01 March 2012
Mesna compared with continuous bladder irrigation as uroprotection during high-dose chemotherapy and transplantation: a randomized trial.
Authors: J M Vose, E C Reed, G C Pippert, J R Anderson, P J Bierman, A Kessinger, J Spinolo, J O Armitage
Journal: Journal of Clinical Oncology (1993)

PURPOSE To compare the use of intravenous (IV) hydration plus either continuous bladder irrigation or mesna for the prevention of hemorrhagic cystitis in the bone marrow transplant setting. PATIENTS AND METHODS Two hundred patients were prospectively randomized to receive either continuous bladder irrigation with 200 mL/h of normal saline, or continuous infusion mesna at 100% of the cyclophosphamide dose. RESULTS The overall incidence of hematuria of any grade was significantly higher in the bladder-irrigation group (76%) compared with the mesna group (53%) (P = .007). However, the incidence of grade III and IV hematuria was the same in both groups (18%; P = NS). Moderate or severe discomfort or bladder spasms were reported in 84% of the patients who received bladder irrigation, compared with 2% of the patients who received mesna prophylaxis (P &lt; .0001). Urinary tract infections (UTIs) were documented in 27% of the patients in the bladder-irrigation group, compared with 14% of the patients in the mesna group (P = .03). CONCLUSION Both continuous bladder irrigation and mesna were equally effective in preventing severe hemorrhagic cystitis associated with high-dose cyclophosphamide and bone marrow transplantation. However, the use of mesna was associated with significantly less discomfort and a lower incidence of UTIs.