tbuckley/cabot-search huggingface dataset:
Changes in Forced Expiratory Volume in 1 Second over Time in COPD
Authors: Jørgen Vestbo, Lisa D. Edwards, Paul D. Scanlon, Julie C. Yates, Alvar Agusti, Per Bakke, Peter M.A. Calverley, Bartolome Celli, Harvey O. Coxson, Courtney Crim, David A. Lomas, William MacNee, Bruce E. Miller, Edwin K. Silverman, Ruth Tal-Singer, Emiel Wouters, Stephen I. Rennard
Journal: New England Journal of Medicine (2011)

A key feature of chronic obstructive pulmonary disease (COPD) is an accelerated rate of decline in forced expiratory volume in 1 second (FEV(1)), but data on the variability and determinants of this change in patients who have established disease are scarce.We analyzed the changes in FEV(1) after administration of a bronchodilator over a 3-year period in 2163 patients. A random-coefficient model was used to evaluate possible predictors of both FEV(1) levels and their changes over time.The mean (±SE) rate of change in FEV(1) was a decline of 33±2 ml per year, with significant variation among the patients studied. The between-patient standard deviation for the rate of decline was 59 ml per year. Over the 3-year study period, 38% of patients had an estimated decline in FEV(1) of more than 40 ml per year, 31% had a decline of 21 to 40 ml per year, 23% had a change in FEV(1) that ranged from a decrease of 20 ml per year to an increase of 20 ml per year, and 8% had an increase of more than 20 ml per year. The mean rate of decline in FEV(1) was 21±4 ml per year greater in current smokers than in current nonsmokers, 13±4 ml per year greater in patients with emphysema than in those without emphysema, and 17±4 ml per year greater in patients with bronchodilator reversibility than in those without reversibility.The rate of change in FEV(1) among patients with COPD is highly variable, with increased rates of decline among current smokers, patients with bronchodilator reversibility, and patients with emphysema.
Airway Basal Stem/Progenitor Cells Have Diminished Capacity to Regenerate Airway Epithelium in Chronic Obstructive Pulmonary Disease
Authors: Michelle R. Staudt, Lauren J. Buro-Auriemma, Matthew S. Walters, Jacqueline Salit, Thomas Vincent, Renat Shaykhiev, Jason G. Mezey, Ann E. Tilley, Robert J. Kaner, Melisa W. Y. Ho, Ronald G. Crystal
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Obstructive sleep apnea (OSA) is a highly prevalent condition throughout the lifespan, affecting 2-10% of the general population at any given age.It is associated with an extensive array of cognitive, behavioral, metabolic, and cardiovascular morbidities
Primary Allogeneic T-Cell Responses against Mantle Cell Lymphoma Antigen-Presenting Cells for Adoptive Immunotherapy after Stem Cell Transplantation
Authors: Mels Hoogendoorn, Judith Olde Wolbers, Willem M. Smit, M. Ronald Schaafsma, Inge Jedema, Renee M.Y. Barge, Roel Willemze, J.H. Frederik Falkenburg
Journal: Clinical Cancer Research (2005)

In patients treated with allogeneic stem cell transplantation for advanced mantle cell lymphoma (MCL), complete sustained remissions have been observed illustrating susceptibility of MCL cells to a graft-versus-lymphoma effect. To potentiate this graft-versus-lymphoma effect, adoptive transfer of in vitro selected MCL-specific CTL can be an attractive approach. The lack of expression of costimulatory molecules on MCL cells hampers the generation of MCL-reactive T-cell responses. The purpose of this study was to modify MCL cells into antigen-presenting cells (APC) and to use these MCL-APCs to induce allogeneic MCL-reactive T-cell responses.Interleukin (IL)-4, IL-10, CpG, and CD40 activation were tested for their capacity to up-regulate costimulatory molecules on MCL cells. Primary MCL cells or the modified MCL-APCs were then used to evaluate the induction of MCL-reactive T-cell responses in HLA-matched donors.Ligation of CD40 on MCL cells was essential to up-regulate costimulatory molecules and to induce production of high amounts of IL-12. In contrast to primary MCL cells, MCL-APC cells as stimulators were capable of inducing CD8+ CTL lines from HLA class I-matched donors. High numbers of CTL clones could be generated capable of efficiently killing the primary MCL cells and MCL-APC but not donor-specific targets.These results show the feasibility to generate primary allogeneic T-cell responses against MCL-APC, and may provide new immunotherapeutic tools to further exploit the graft-versus-lymphoma effect following allogeneic stem cell transplantation in patients with MCL.
THE IN VITRO PREPARATION AND HISTOCHEMICAL PROPERTIES OF SUBSTANCES RESEMBLING CEROID
Authors: W. G. Bruce Casselman
Journal: The Journal of Experimental Medicine (1951)

Substances possessing the same histochemical properties as the ceroid in cirrhotic livers of rats fed choline-deficient diets have been prepared from various unsaturated fats, fatty acids and their esters by autoxidation but could not be obtained from hydrocarbons or saturated fats or fatty acids. The formation of ceroid-like substances occurred first on surfaces or at interfaces in the reaction mixtures. It was inhibited by antioxidants and was accelerated by the addition of tissues, blood cells, erythrocytic stroma, or hemoglobin, by emulsification, by increasing the surface exposed to the air, and by increasing the temperature. Histochemical studies provided much evidence that the following properties of ceroid might be attributed to the products of the autoxidation of unsaturated lipids: insolubility in organic solvents, sudanophilia, yellowing by concentrated nitric acid, positive periodic acid-Schiff's reaction, basophilia, acid fastness, positive hernofuscin reaction, and reduction of diammine silver carbonate and alkaline potassium permanganate. The normal reactivity of cells or tissues embedded in ceroid was effectively masked by the pigment, apparently, initially at least, by preventing the reagents' gaining access to them. It is suggested that the iron sometimes demonstrated in ceroid may be that of blood cells or tissue fragments incompletely masked by the ceroid. It is concluded that whenever conditions are such that unsaturated fats accumulate in tissues to such an extent that a relative lack of biological anti-oxidants results, autoxidation of the fats and their conversion to ceroid pigment are favored, and that ceroid and the lipofuscin pigment of vitamin E deficiency may be fundamentally similar.
Loss of ATP Diphosphohydrolase Activity with Endothelial Cell Activation
Authors: Simon C. Robson, Elzbieta Kaczmarek, Jonathan B. Siegel, Daniel Candinas, Katarzyna Koziak, Maria Millan, Wayne W. Hancock, Fritz H. Bach
Journal: The Journal of Experimental Medicine (1997)

Quiescent endothelial cells (EC) regulate blood flow and prevent intravascular thrombosis. This latter effect is mediated in a number of ways, including expression by EC of thrombomodulin and heparan sulfate, both of which are lost from the EC surface as part of the activation response to proinflammatory cytokines. Loss of these anticoagulant molecules potentiates the procoagulant properties of the injured vasculature. An additional thromboregulatory factor, ATP diphosphohydrolase (ATPDase; designated as EC 3.6.1.5) is also expressed by quiescent EC, and has the capacity to degrade the extracellular inflammatory mediators ATP and ADP to AMP, thereby inhibiting platelet activation and modulating vascular thrombosis. We describe here that the antithrombotic effects of the ATPDase, like heparan sulfate and thrombomodulin, are lost after EC activation, both in vitro and in vivo. Because platelet activation and aggregation are important components of the hemostatic changes that accompany inflammatory diseases, we suggest that the loss of vascular ATPDase may be crucial for the progression of vascular injury.
Deficiency of Antigen-Presenting Cell Invariant Chain Reduces Atherosclerosis in Mice
Authors: Jiusong Sun, Karsten Hartvigsen, Meng-Yun Chou, Yadong Zhang, Galina K. Sukhova, Jie Zhang, Marco Lopez-Ilasaca, Cody J. Diehl, Niva Yakov, Dror Harats, Jacob George, Joseph L. Witztum, Peter Libby, Hidde Ploegh, Guo-Ping Shi
Journal: Circulation (2010)

Adaptive immunity and innate immunity play important roles in atherogenesis. Invariant chain (CD74) mediates antigen-presenting cell antigen presentation and T-cell activation. This study tested the hypothesis that CD74-deficient mice have reduced numbers of active T cells and resist atherogenesis.In low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice, CD74 deficiency (Ldlr(-/-)Cd74(-/-)) significantly reduced atherosclerosis and CD25(+)-activated T cells in the atheromata. Although Ldlr(-/-)Cd74(-/-) mice had decreased levels of plasma immunoglobulin (Ig) G1, IgG2b, and IgG2c against malondialdehyde-modified LDL (MDA-LDL), presumably as a result of impaired antigen-presenting cell function, Ldlr(-/-)Cd74(-/-) mice showed higher levels of anti-MDA-LDL IgM and IgG3. After immunization with MDA-LDL, Ldlr(-/-)Cd74(-/-) mice had lower levels of all anti-MDA-LDL Ig isotypes compared with Ldlr(-/-) mice. As anticipated, only Ldlr(-/-) splenocytes responded to in vitro stimulation with MDA-LDL, producing Th1/Th2 cytokines. Heat shock protein-65 immunization enhanced atherogenesis in Ldlr(-/-) mice, but Ldlr(-/-) Cd74(-/-) mice remained protected. Compared with Ldlr(-/-) mice, Ldlr(-/-)Cd74(-/-) mice had higher anti-MDA-LDL autoantibody titers, fewer lesion CD25(+)-activated T cells, impaired release of Th1/Th2 cytokines from antigen-presenting cells after heat shock protein-65 stimulation, and reduced levels of all plasma anti-heat shock protein-65 Ig isotypes. Cytofluorimetry of splenocytes and peritoneal cavity cells of MDA-LDL- or heat shock protein-65-immunized mice showed increased percentages of autoantibody-producing marginal zone B and B-1 cells in Ldlr(-/-)Cd74(-/-) mice compared with Ldlr(-/-) mice.Invariant chain deficiency in Ldlr(-/-) mice reduced atherosclerosis. This finding was associated with an impaired adaptive immune response to disease-specific antigens. Concomitantly, an unexpected increase in the number of innate-like peripheral B-1 cell populations occurred, resulting in increased IgM/IgG3 titers to the oxidation-specific epitopes.
Generation of Hydroxyl Radical by Enzymes, Chemicals, and Human Phagocytes In Vitro
Authors: John E. Repine, John W. Eaton, M. W. Anders, John R. Hoidal, Richard B. Fox
Journal: Journal of Clinical Investigation (1979)

Methane (CH4) production from the anti-inflammatory agent, dimethyl sulfoxide (DMSO), was used to measure ·OH from chemical reactions or human phagocytes. Reactions producing ·OH (xanthine/xanthine oxidase or Fe++/EDTA/H2O2) generated CH4 from DMSO, whereas reactions yielding primarily O-2̇ or H2O2 failed to produce CH4. Neutrophils (PMN), monocytes, and alveolar macrophages also produced CH4 from DMSO. Mass spectroscopy using d6-DMSO showed formation of d3-CH4 indicating that CH4 was derived from DMSO. Methane generation by normal but not chronic granulomatous disease or heat-killed phagocytes increased after stimulation with opsonized zymosan particles or the chemical, phorbol myristate acetate. Methane production from DMSO increased as the number of stimulated PMN was increased and the kinetics of CH4 production approximated other metabolic activities of stimulated PMN. Methane production from stimulated phagocytes and DMSO was markedly decreased by purportedly potent ·OH scavengers (thiourea or tryptophane) and diminished to lesser degrees by weaker ·OH scavengers (mannitol, ethanol, or sodium benzoate). Superoxide dismutase or catalase also decreased CH4 production but urea, albumin, inactivated superoxide dismutase, or boiled catalase had no appreciable effect. The results suggest that the production of CH4 from DMSO may reflect release of ·OH from both chemical systems and phagocytic cells. Interaction of the nontoxic, highly permeable DMSO with ·OH may explain the anti-inflammatory actions of DMSO and provide a useful measurement of ·OH in vitro and in vivo.
Dual effect of serotonin on growth of bovine pulmonary artery smooth muscle cells in culture.
Authors: S L Lee, W W Wang, B J Moore, B L Fanburg
Journal: Circulation Research (1991)

We have previously reported that serotonin (5-hydroxytryptamine [5HT]) alters cultured bovine pulmonary artery smooth muscle cell (SMC) configuration through two different regulatory mechanisms. We now report that 5HT also regulates SMC growth through these same two mechanisms--a stimulatory event initiated intracellularly and inhibition of growth resulting from a cell surface action. 5HT (1 microM) plus 0.1 mM iproniazid (a 5HT metabolic inhibitor) produced a severalfold stimulation of DNA synthesis (as measured by [3H]thymidine incorporation) of SMCs after a 17-24-hour incubation with only a slight elevation of cellular cAMP. This stimulatory effect responded synergistically with other growth factors including platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor and was effectively reversed by 5HT uptake inhibition. It was not produced by 5-hydroxyindoleacetic acid, a metabolite of 5HT. In the presence of 1 microM 5HT plus 0.1 mM isobutylmethylxanthine (IBMX), cAMP was elevated eightfold, dendritic formation occurred, and [3H]thymidine labeling of SMCs was inhibited. Inhibition of labeling by [3H]thymidine was mimicked by other agents that elevated cellular cAMP (10 microM histamine, 1 microM isoproterenol plus 0.1 mM IBMX, and 10 microM forskolin) and by 1 mM dibutyryl cAMP. This inhibitory effect was not blocked by either inhibition of 5HT uptake or 5HT-receptor antagonists ketanserin (5HT2); methiothepin, spiperone, and mianserin (5HT1/5HT2); and 3-tropanyl-indole-3-carboxylate and 3-tropanyl-3,5-dichlorobenzoate (5HT3). However, similar to 5HT, the 5HT1A agonist, (+/-)-8-hydroxy-(+/-)-2-dipropylamino-8-hydroxy-1,2,3, 4-tetrahydronaphthalenehydrobromide, in association with IBMX, produced an elevation in cAMP and inhibition of labeling by [3H]thymidine. 5HT, in the presence of either iproniazid or IBMX, did not alter [Ca2+]i, indicating that [Ca2+]i was not a signal for either of these actions.(ABSTRACT TRUNCATED AT 250 WORDS)
Founder von Willebrand factor haplotype associated with type 1 von Willebrand disease
Authors: Lee A. O'Brien, Paula D. James, Maha Othman, Ergul Berber, Cherie Cameron, Colleen R. P. Notley, Carol A. Hegadorn, Jeffrey J. Sutherland, Christine Hough, Georges E. Rivard, Denise O'Shaunessey, David Lillicrap
Journal: Blood (2003)
Long-term survival of patients with unresectable colorectal cancer liver metastases following infusional chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and surgery
Authors: S. Giacchetti, M. Itzhaki, G. Gruia, R. Adam, R. Zidani, F. Kunstlinger, S. Brienza, E. Alafaci, F. Bertheault-Cvitkovic, C. Jasmin, M. Reynes, H. Bismuth, J.L. Misset, F. Lévi
Journal: Annals of Oncology (1999)
Failure of once daily inhaled corticosteroid treatment to control chronic asthma.
Authors: D V McGivern, M Ward, J T Macfarlane, W H Roderick Smith
Journal: Thorax (1984)

Twelve patients with chronic asthma received either high dose beclomethasone once a day or standard doses of beclomethasone three times a day in a double blind crossover trial to determine whether inhalation once a day would be sufficient. With the once a day regimen peak expiratory flow rates fell significantly, symptoms of nocturnal asthma increased, and two patients withdrew from the study because of worsening asthma. Whether control can be achieved with steroids inhaled once a day by simply increasing the total daily dose remains to be seen.
Predicting Response to Radioimmunotherapy from the Tumor Microenvironment of Colorectal Carcinomas
Authors: Ethaar El Emir, Uzma Qureshi, Jason L.J. Dearling, Geoffrey M. Boxer, Innes Clatworthy, Amos A. Folarin, Mathew P. Robson, Sylvia Nagl, Moritz A. Konerding, R. Barbara Pedley
Journal: Cancer Research (2007)

Abstract Solid tumors have a heterogeneous pathophysiology, which directly affects antibody-targeted therapies. Here, we consider the influence of selected tumor parameters on radioimmunotherapy, by comparing the gross biodistribution, microdistribution, and therapeutic efficacy of either radiolabeled or fluorescently labeled antibodies (A5B7 anti–carcinoembryonic antigen antibody and a nonspecific control) after i.v. injection in two contrasting human colorectal xenografts in MF1 nude mice. The LS174T is moderately/poorly differentiated, whereas SW1222 has a well-differentiated glandular structure. Biodistribution studies (1.8 MBq 131I-labeled A5B7, four mice per group) showed similar gross tumor uptake at 48 h in the two models (25.1% and 24.0% injected dose per gram, respectively). However, in therapy studies (six mice per group), LS174T required a 3-fold increase in dose (18 versus 6 MBq) to equal SW1222 growth inhibition (∼55 versus ∼60 days, respectively). To investigate the basis of this discrepancy, high-resolution multifluorescence microscopy was used to study antibody localization in relation to tumor parameters (5 min, 1 and 24 h, four mice per time point). Three-dimensional microvascular corrosion casting and transmission electron microscopy showed further structural differences between xenografts. Vascular supply, overall antigen distribution, and tumor structure varied greatly between models, and were principally responsible for major differences in antibody localization and subsequent therapeutic efficacy. The study shows that multiparameter, high-resolution imaging of both therapeutic and tumor microenvironment is required to comprehend complex antibody-tumor interactions, and to determine which tumor regions are being successfully treated. This will inform the design of optimized clinical trials of single and combined agents, and aid individual patient selection for antibody-targeted therapies. [Cancer Res 2007;67(24):11896–905]
Androgen Deprivation Therapy for Node-Positive Prostate Cancer: Adjuvant Does Not Mean Salvage
Authors: Stéphane Culine
Journal: Journal of Clinical Oncology (2009)

TO THE EDITOR: I read with interest the study by Wong et al on the role of androgen deprivation therapy (ADT) in patients who had metastatic regional lymph nodes after radical prostatectomy. As mentioned by the authors, the results of the randomized trial by Messing et al showing a significant advantage in progression-free survival and overall survival in patients who received immediate (rather than delayed at time of metastasis) ADT have led to the standard use of adjuvant ADT for node-positive patients. However, this study was conducted before the prostate-specific antigen (PSA) era and the contemporary practice of surveillance policy with salvage ADT at biochemical recurrence. Therefore, the benefit of adjuvant ADT is not clear, and additional investigations are required. Unfortunately, the methodology used by Wong et al does not allow any useful conclusion to be drawn. Indeed, the major limitation is the absence of data regarding PSA values at onset of ADT. Was ADT administered as an adjuvant treatment in patients who achieved undetectable PSA after surgery or as salvage treatment in patients with biochemical recurrence? For an adjuvant therapy, the choice of 120 days is obviously not optimal. In general oncology, adjuvant treatment is required as soon as possible after local therapy. In prostate cancer, ADT is supposed to be initiated within 8 weeks after surgery (ie, after reaching PSA value 0.1 ng/mL). Therefore, it is highly suspected that patients who received ADT within 120 days of prostatectomy had undetectable (adjuvant ADT) or detectable (salvage ADT) PSA. In my opinion, 150 days or more after prostatectomy, the whole population of patients would have had detectable PSA. Consequently, the reported data do not provide any convincing information regarding the role of adjuvant ADT. The only conclusion can be that in the PSA era, the overall and cancer-specific survivals at 10 years for patients treated with adjuvant ADT or salvage ADT do not seem different from those observed in patients not treated with ADT after prostatectomy.
Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes
Authors: Julius Gudmundsson, Patrick Sulem, Valgerdur Steinthorsdottir, Jon T Bergthorsson, Gudmar Thorleifsson, Andrei Manolescu, Thorunn Rafnar, Daniel Gudbjartsson, Bjarni A Agnarsson, Adam Baker, Asgeir Sigurdsson, Kristrun R Benediktsdottir, Margret Jakobsdottir, Thorarinn Blondal, Simon N Stacey, Agnar Helgason, Steinunn Gunnarsdottir, Adalheidur Olafsdottir, Kari T Kristinsson, Birgitta Birgisdottir, Shyamali Ghosh, Steinunn Thorlacius, Dana Magnusdottir, Gerdur Stefansdottir, Kristleifur Kristjansson, Yu Bagger, Robert L Wilensky, Muredach P Reilly, Andrew D Morris, Charlotte H Kimber, Adebowale Adeyemo, Yuanxiu Chen, Jie Zhou, Wing-Yee So, Peter C Y Tong, Maggie C Y Ng, Torben Hansen, Gitte Andersen, Knut Borch-Johnsen, Torben Jorgensen, Alejandro Tres, Fernando Fuertes, Manuel Ruiz-Echarri, Laura Asin, Berta Saez, Erica van Boven, Siem Klaver, Dorine W Swinkels, Katja K Aben, Theresa Graif, John Cashy, Brian K Suarez, Onco van Vierssen Trip, Michael L Frigge, Carole Ober, Marten H Hofker, Cisca Wijmenga, Claus Christiansen, Daniel J Rader, Colin N A Palmer, Charles Rotimi, Juliana C N Chan, Oluf Pedersen, Gunnar Sigurdsson, Rafn Benediktsson, Eirikur Jonsson, Gudmundur V Einarsson, Jose I Mayordomo, William J Catalona, Lambertus A Kiemeney, Rosa B Barkardottir, Jeffrey R Gulcher, Unnur Thorsteinsdottir, Augustine Kong, Kari Stefansson
Journal: Nature Genetics (2007)
Growth hormone, menopause and ageing: no definite evidence for 'rejuvenation' with growth hormone
Authors: G. Fanciulli, A. Delitala, G. Delitala
Journal: Human Reproduction Update (2009)

BACKGROUNDEstrogens regulate growth hormone (GH) secretion and modulate the tissue responsiveness to GH. After the menopause, and during ageing, a decline in GH secretion (somatopause) is physiologically observed. This article (i) provides a brief overview of the different regulators of GH secretion, (ii) reviews the mechanisms involved in age-related changes in GH concentrations, with particular emphasis on the interrelationships between menopause and GH, and (iii) discusses the interventions aimed at the restoration of GH and insulin-like growth factor (IGF-1) circulating levels.
Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study
Authors: Henryk Barthel, Hermann-Josef Gertz, Stefan Dresel, Oliver Peters, Peter Bartenstein, Katharina Buerger, Florian Hiemeyer, Sabine M Wittemer-Rump, John Seibyl, Cornelia Reininger, Osama Sabri
Journal: The Lancet Neurology (2011)
HER2-Affitoxin: A Potent Therapeutic Agent for the Treatment of HER2-Overexpressing Tumors
Authors: Rafal Zielinski, Ilya Lyakhov, Moinuddin Hassan, Monika Kuban, Kimberly Shafer-Weaver, Amir Gandjbakhche, Jacek Capala
Journal: Clinical Cancer Research (2011)

Cancers overexpressing the HER2/neu gene are usually more aggressive and are associated with poor prognosis. Although trastuzumab has significantly improved the outcome, many tumors do not respond or acquire resistance to current therapies. To provide an alternative HER2-targeted therapy, we have developed and characterized a novel recombinant protein combining an HER2-specific Affibody and modified Pseudomonas aeruginosa exotoxin A (PE 38), which, after binding to HER2, is internalized and delivered to the cytosol of the tumor cell, where it blocks protein synthesis by ADP ribosylation of eEF-2.