tbuckley/cabot-search huggingface dataset:
High incidence of disease recurrence after discontinuation of disease-modifying antirheumatic drug treatment in patients with psoriatic arthritis in remission
Authors: Elizabeth G Araujo, Stephanie Finzel, Matthias Englbrecht, Dominik A Schreiber, Francesca Faustini, Axel Hueber, Kemal Nas, Juergen Rech, Georg Schett
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To investigate the possibility of drug-free remission in patients with psoriatic arthritis (PsA) in continuous remission. <h3>Methods</h3> Prospective observational study in disease-modifying antirheumatic drug (DMARD)-treated PsA patients in continuous disease remission (no musculoskeletal symptoms, no or minimal skin/nail disease) for at least 6 months. Demographic, disease-specific and ultrasound parameters were assessed at baseline. DMARDs (traditional or biologic) were discontinued at the initial visit, and patients were followed for a maximum of 6 months for recurrence of disease. <h3>Results</h3> 26 patients (methotrexate monotherapy: N=14; tumour necrosis factor inhibitors: N=12) with a mean age of 55.2 years, absence of musculoskeletal symptoms and minimal skin disease (mean Psoriasis Area Severity Index (PASI): 0.21) were enrolled. Incidence of recurrence of disease was high (N=20, 76.9%) and occurred rapidly (74.50±51.72 days) after treatment discontinuation. Male PsA patients were significantly more likely to lose remission. Long disease duration, more severe skin involvement and the presence of synovial hypertrophy by ultrasonographic examination at baseline decreased the likelihood for drug-free remission. Reinitiation of DMARDs promptly restored remission in all PsA patients with recurrence of disease. <h3>Conclusions</h3> This study shows that the chance to reach drug-free remission in PsA patients is low. Discontinuation of DMARD therapy cannot be recommended in patients with PsA.
Effects of vitamin C on airway responsiveness to inhaled histamine in heavy smokers
Authors: C Bucca, G Rolla, E Caria, W Arossa, M Bugiani
Journal: European Respiratory Journal (1989)

Histamine bronchial threshold, the provocation concentration of histamine causing a 25% fall in maximal expiratory flow at 50% of forced vital capacity from the control value (PC25MEF50), was measured in seven heavy smokers and in seven sex- and age-matched nonsmokers before and one hour after ingestion, double-blind, of vitamin C (2 g) or placebo. Smokers had significantly lower baseline values of serum ascorbate, maximal expiratory flow at 50% of forced vital capacity (MEF50) and PC25MEF50: the latter was negatively related to serum ascorbate (r = -0.85; p less than 0.001). Acute treatment with vitamin C produced a significant decrease in PC25MEF50 in smokers (95% confidence limit (CL) from 4.87-3.36 to 2.91-2.01 mg.ml-1; p = 0.017), whilst it had no effect in nonsmokers. A preliminary open study on the effect of prolonged administration of vitamin C (1 g daily) was performed in smokers. One week of treatment produced a further significant decrease in PC25MEF50 (p less than 0.0001). Our results suggest that in heavy smokers histamine bronchial responsiveness may be attenuated by chronic ascorbate deficiency. In these circumstances, acute and short-term treatment with vitamin C may increase the bronchoconstrictive response to inhaled histamine.
The Ultrastructure of Glomerular Filtration
Authors: M J Karnovsky
Journal: Annual Review of Medicine (1979)

The glomeruli of the kidney serve to separate about one third of the plasma entering them into a virtually ideal ultrafiltrate. To accomplish this, fluid is driven by hydraulic forces across the glomerular capillary wall (GCW), which has a high permeability to water but virtually excludes molecules larger than albumin from the filtrate. In recent years it has become apparent that the glomerulus is not merely a mechanical filter but that it is an organ of extreme complexity and subtle behavior. It is the purpose of this brief review to cover the physiological and morphological observations underlying our current concepts of the struc­ tural bases for glomerular filtration.
Protective effect of 55- but not 75-kD soluble tumor necrosis factor receptor-immunoglobulin G fusion proteins in an animal model of gram-negative sepsis.
Authors: T J Evans, D Moyes, A Carpenter, R Martin, H Loetscher, W Lesslauer, J Cohen
Journal: The Journal of Experimental Medicine (1994)

The aim of this study was to compare the ability of both a 55- and 75-kD soluble tumor necrosis factor receptor immunoglobulin G fusion protein (sTNFR-IgG) in protecting against death in a murine model of gram-negative sepsis. Pretreatment with 250 micrograms of the p75 construct delayed but did not avert death in this model, reducing peak bioactive TNF-alpha levels after infection from 76.4 ng ml-1 in control mice to 4.7 ng ml-1 in the treated group (p &amp;lt; 0.05, two-sample t test). However, these low levels of bioactive TNF-alpha persisted in the p75 fusion protein-treated animals compared with the controls and were sufficient to mediate delayed death. In contrast, pretreatment with 200 micrograms of the p55 sTNFR-IgG gave excellent protection against death with complete neutralization of circulating TNF. Studies of the binding of TNF-alpha with the soluble TNFR fusion proteins showed that the p75 fusion construct exchanges bound TNF-alpha about 50-100-fold faster than the p55 fusion protein. Thus, although both fusion proteins in equilibrium bind TNF-alpha with high affinity, the TNF-alpha p55 fusion protein complex is kinetically more stable than the p75 fusion construct, which thus acts as a TNF carrier. The persistent release of TNF-alpha from the p75 fusion construct limits its therapeutic effect in this model of sepsis.
Prevalence of childhood asthma, rhinitis and eczema in Scandinavia and Eastern Europe
Authors: B Bjorksten, D Dumitrascu, T Foucard, N Khetsuriani, R Khaitov, M Leja, G Lis, J Pekkanen, A Priftanji, MA Riikjarv
Journal: European Respiratory Journal (1998)

There is evidence that the prevalence of allergies and asthma differs between populations in western and eastern Europe. This study investigated the prevalence of wheezing, rhinitis and eczema among schoolchildren in urban and rural areas of Scandinavia and the formerly socialist countries of Eastern Europe. A total of 79,000 children from two age groups (13-14 yrs and 6-7 yrs) in 18 study centres responded to a questionnaire within the International Study of Asthma and Allergy in Children (ISAAC). The 12 month period prevalence of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema was calculated. The prevalence of wheezing among the 13-14 yr old children was 11.2-19.7% in Finland and Sweden, 7.6-8.5% in Estonia, Latvia and Poland and 2.6-5.9% in Albania, Romania, Russia, Georgia and Uzbekistan (except Samarkand). The prevalence of itching eyes and flexural dermatitis varied in a similar manner between the three regions. The regional differences were less pronounced among the 6-7 yr old children in the seven participating centres. The highest prevalence of rhinitis was recorded in April-July in Scandinavia and during the winter months in the other countries. The prevalence of atopy-related disorders was higher in Scandinavia than in Estonia, Latvia and Poland, which in turn had a higher prevalence than five other countries of eastern Europe with a culture less similar to western Europe. This supports the hypothesis that "Western life style" is associated with a high prevalence of childhood allergy.
The NCGC Pharmaceutical Collection: A Comprehensive Resource of Clinically Approved Drugs Enabling Repurposing and Chemical Genomics
Authors: Ruili Huang, Noel Southall, Yuhong Wang, Adam Yasgar, Paul Shinn, Ajit Jadhav, Dac-Trung Nguyen, Christopher P. Austin
Journal: Science Translational Medicine (2011)

Small-molecule compounds approved for use as drugs may be "repurposed" for new indications and studied to determine the mechanisms of their beneficial and adverse effects. A comprehensive collection of all small-molecule drugs approved for human use would be invaluable for systematic repurposing across human diseases, particularly for rare and neglected diseases, for which the cost and time required for development of a new chemical entity are often prohibitive. Previous efforts to build such a comprehensive collection have been limited by the complexities, redundancies, and semantic inconsistencies of drug naming within and among regulatory agencies worldwide; a lack of clear conceptualization of what constitutes a drug; and a lack of access to physical samples. We report here the creation of a definitive, complete, and nonredundant list of all approved molecular entities as a freely available electronic resource and a physical collection of small molecules amenable to high-throughput screening.
Reply: Bacille Calmette-Guérin Vaccine: Innate Immunity and Nonspecific Effects
Authors: Nicole Ritz, Dan Casalaz, Willem A. Hanekom, Warwick J. Britton, Binita Dutta, Susan Donath, Tom G. Connell, Marc Tebruegge, Roy Robins-Browne, Nigel Curtis
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
In vivo technetium-99m S12 antibody imaging of platelet alpha-granules in rabbit endothelial neointimal proliferation after angioplasty.
Authors: D D Miller, A J Boulet, F O Tio, O J Garcia, D M Guy, R P McEver, J C Palmaz, K Y Pak, D S Neblock, H J Berger
Journal: Circulation (1991)

To examine the specificity of technetium-99m monoclonal antibody (S12) imaging for identifying activated platelets at interventional injury sites in atherosclerotic rabbit arteries, subgroups of unheparinized rabbits (n = 39) underwent serial percutaneous transluminal aortic angioplasty (PTA) procedures (with or without intravascular stent placement) followed by in vivo and then ex vivo gamma camera imaging, scanning, and immunoelectron microscopy to determine the intravascular loci of S12 Fab' antibody binding. Despite angiographic vessel patency, image-derived ratios of in vivo S12 binding in injured versus uninjured vascular segments were significantly increased (p less than 0.05) after one PTA (1.3 +/- 0.17, n = 7), PTA twice at 6-week intervals (1.4 +/- 0.22, n = 7), and PTA plus stent placement (1.6 +/- 0.28, n = 7) compared with control experiments (1.1 +/- 0.13, n = 7). Ex vivo imaging of blood-free excised aortas confirmed S12 localization at PTA (2 +/- 0.4, n = 3) and PTA plus stent placement (5 +/- 3.8, n = 7) sites (both p less than 0.05 versus controls). S12 antibody uptake decreased significantly (p less than 0.05) at 1 week after PTA plus stent placement in vivo (1.1 +/- 0.10, n = 4) and ex vivo (1.6 +/- 0.7, n = 3). Electron microscopic studies confirmed dense platelet, fibrin, and red blood cell deposition in regions of acute injury, with endothelial neointimal proliferation at 1 week after PTA. Immunoelectron microscopic studies confirmed specific in vivo S12 binding (22:1 versus nonrelevant IgG) at sites of alpha-granule GMP-140 expression in activated platelets. Therefore, S12 studies may be useful to localize sites of platelet-derived mitogen release at arterial PTA injury sites.
Hydrogen Peroxide–Scavenging Properties of Normal Human Airway Secretions
Authors: Souheil El-Chemaly, Matthias Salathe, Sylvia Baier, Gregory E. Conner, Rosanna Forteza
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

To examine the antioxidant capacity of normal human airway secretions and to characterize its molecular components, tracheal lavages were obtained from eight patients intubated for elective surgery and free of lung disease. These samples (20 microl, approximately 6.8 microg of protein) scavenged 0.57 +/- 0.09 nmol of added 0.96 nmol hydrogen peroxide (H2O2) within 10 minutes at room temperature (n = 8). The scavenging activity was inhibited 60 +/- 4% by azide (an inhibitor of heme-containing peroxidases and catalase) and 42 +/- 9% by dapsone (an inhibitor of lactoperoxidase). Mercaptosuccinic acid (an inhibitor of glutathione peroxidase) did not significantly inhibit H2O2 scavenging by these secretions. Fourfold diluted secretions showed only nonenzymatic scavenging activity, but the addition of thiocyanate to these samples (0.4 mM; substrate for lactoperoxidase) restored their ability to scavenge H2O2. The addition of reduced glutathione (8 microM) only enhanced nonenzymatic scavenging activity. These data provide evidence that multiple enzymatic and nonenzymatic systems coexist in human airway secretions that contribute to H2O2 scavenging. It appears, however, that H2O2 is mainly consumed by the lactoperoxidase system.
Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: a case-control study
Authors: Eric M Reiman, Yakeel T Quiroz, Adam S Fleisher, Kewei Chen, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio, Anne M Fagan, Aarti R Shah, Sergio Alvarez, Andrés Arbelaez, Margarita Giraldo, Natalia Acosta-Baena, Reisa A Sperling, Brad Dickerson, Chantal E Stern, Victoria Tirado, Claudia Munoz, Rebecca A Reiman, Matthew J Huentelman, Gene E Alexander, Jessica BS Langbaum, Kenneth S Kosik, Pierre N Tariot, Francisco Lopera
Journal: The Lancet Neurology (2012)
Tumour necrosis factor alpha potentiates ion secretion induced by histamine in a human intestinal epithelial cell line and in mouse colon: involvement of the phospholipase D pathway
Authors: J C J Oprins
Journal: Gut (2002)

Background and aims: Patients suffering from inflammatory bowel disease show increased levels of the mast cell products histamine and tumour necrosis factor α (TNF-α). Treating these patients with antibodies against TNF-α diminishes the symptoms of diarrhoea. In this study, the effect of TNF-α on ion secretion induced by the mast cell mediator histamine in HT29cl.19A cells and mouse distal colon was investigated and the possible second messengers involved were studied. Methods: Electrophysiology of filter grown HT29cl.19A cells and isolated mouse distal colon was used to monitor the secretory response to histamine with and without prior exposure to TNF-α for 3–24 hours. Phospholipase D (PLD) activity and phosphatidic acid levels were analysed by <sup>32</sup>P<sub>i</sub> labelling of HT29cl.19A cells. Results: In both experimental systems TNF-α was found to potentiate ion secretion induced by histamine. Phospholipid analysis of HT29cl.19A cells revealed that histamine activates the PLD pathway. Furthermore, TNF-α pretreated cells were found to have decreased phosphatidic acid levels, the intermediate product of the PLD pathway, which indicates upregulation of the enzyme phosphatidic acid phosphatase. Conclusions: The mast cell products TNF-α and histamine synergistically stimulate ion secretion in intestinal epithelium via upregulation of the PLD pathway.
Relation of Consumption of Vitamin E, Vitamin C, and Carotenoids to Risk for Stroke among Men in the United States
Authors: Alberto Ascherio
Journal: Annals of Internal Medicine (1999)

Antioxidants increase the resistance of low-density lipoprotein to oxidation and may thereby reduce risk for atherosclerosis.To determine whether intake of vitamin E, vitamin C, or carotenoids predict risk for total or ischemic stroke.Prospective observational study.The Health Professionals Follow-up Study.43,738 men 40 to 75 years of age who did not have cardiovascular disease or diabetes.Repeated and validated dietary assessments were done by using a self-administered 131-item food-frequency questionnaire, which included questions on dose and duration of vitamin supplement use. The follow-up period was 8 years.A total of 328 strokes occurred: 210 ischemic, 70 hemorrhagic, and 48 unclassified. After adjustment for age, smoking, hypertension, hypercholesterolemia, body mass index, physical activity, parental history of myocardial infarction, alcohol consumption, and total energy intake, the relative risk for ischemic stroke in the top quintile of vitamin E intake (median, 411 IU/d) compared with the bottom quintile (5.4 IU/d) was 1.18 (95% CI, 0.77 to 1.82). The relative risk for ischemic stroke in the top quintile of vitamin C intake (1167 mg/d) compared with the bottom quintile (95 mg/d) was 1.03 (CI, 0.66 to 1.59). Results for total stroke were similar. Associations of vitamin intake with hemorrhagic stroke were also nonsignificant, but the CIs were wide. Neither dose nor duration of vitamin E or vitamin C supplement use was related to risk for total or ischemic stroke. The relative risk for ischemic stroke was 1.16 (CI, 0.81 to 1.67) in men using 250 IU or more of vitamin E supplementation per day compared with men who used no vitamin E supplements and was 0.93 (CI, 0.60 to 1.45) in men using 700 mg or more of vitamin C supplementation per day compared with men who used no vitamin C supplements. A significant inverse relation between lutein intake and risk for ischemic stroke was seen but was not independent of other dietary factors.Vitamin E and vitamin C supplements and specific carotenoids did not seem to substantially reduce risk for stroke in this cohort. Modest effects, however, cannot be excluded.
Genome Architecture Drives Protein Evolution in Ciliates
Authors: Rebecca A. Zufall, Casey L. McGrath, Spencer V. Muse, Laura A. Katz
Journal: Molecular Biology and Evolution (2006)

Studies of microbial eukaryotes have been pivotal in the discovery of biological phenomena, including RNA editing, self-splicing RNA, and telomere addition. Here we extend this list by demonstrating that genome architecture, namely the extensive processing of somatic (macronuclear) genomes in some ciliate lineages, is associated with elevated rates of protein evolution. Using newly developed likelihood-based procedures for studying molecular evolution, we investigate 6 genes to compare 1) ciliate protein evolution to that of 3 other clades of eukaryotes (plants, animals, and fungi) and 2) protein evolution in ciliates with extensively processed macronuclear genomes to that of other ciliate lineages. In 5 of the 6 genes, ciliates are estimated to have a higher ratio of nonsynonymous/synonymous substitution rates, consistent with an increase in the rate of protein diversification in ciliates relative to other eukaryotes. Even more striking, there is a significant effect of genome architecture within ciliates as the most divergent proteins are consistently found in those lineages with the most highly processed macronuclear genomes. We propose a model whereby genome architecture-specifically chromosomal processing, amitosis within macronuclei, and epigenetics-allows ciliates to explore protein space in a novel manner. Further, we predict that examination of diverse eukaryotes will reveal additional evidence of the impact of genome architecture on molecular evolution.
Effect of HIV infection on pregnancy-related mortality in sub-Saharan Africa: secondary analyses of pooled community-based data from the network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA)
Authors: Basia Zaba, Clara Calvert, Milly Marston, Raphael Isingo, Jessica Nakiyingi-Miiro, Tom Lutalo, Amelia Crampin, Laura Robertson, Kobus Herbst, Marie-Louise Newell, Jim Todd, Peter Byass, Ties Boerma, Carine Ronsmans
Journal: The Lancet (2013)
Response of nasal ciliated cells of the guinea-pig during allergic reactions in human blood
Authors: Y Ohashi, Y Nakai, H Ikeoka, H Koshimo, Y Esaki
Journal: European Respiratory Journal (1988)

Nasal mucosal samples from thirty-five guinea-pigs were placed in a chamber, containing the medium RPMI 1640. Ciliary activity (beats.s-1) of the most active cell in each mucosal culture was measured using a photoelectric method. The RPMI 1640 was then replaced by 2 ml of RPMI 1640 and 1 ml of heparinized human blood from a non-allergic patient, with a ragweed-sensitive nasal allergy, or patients with D. farinae-sensitive nasal allergy: the ciliary activity of the same ciliated cell in each culture did not change significantly. We then added 1 micrograms of D. farinae extracts to evoke an in vitro allergic reaction. Ciliary excitation was induced when D. farinae extracts were added to the blood from D. farinae-sensitive subjects but not when added to blood from subjects without sensitivity to D. farinae. The peak and plateau of such an event occurred after 20-30 min. Ciliary stimulations were correlated with D. farinae-induced histamine release from whole blood. Thus, in vitro allergic reactions stimulate activity in cilia from normal nasal mucosa.
Adjuvant Therapy With Pegylated Interferon Alfa-2b Versus Observation in Resected Stage III Melanoma: A Phase III Randomized Controlled Trial of Health-Related Quality of Life and Symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group
Authors: Andrew Bottomley, Corneel Coens, Stefan Suciu, Mario Santinami, Willem Kruit, Alessandro Testori, Jeremy Marsden, Cornelis Punt, François Salès, Martin Gore, Rona MacKie, Zvonko Kusic, Reinhard Dummer, Poulam Patel, Dirk Schadendorf, Alain Spatz, Ulrich Keilholz, Alexander Eggermont
Journal: Journal of Clinical Oncology (2009)

Purpose Interferon (IFN) -based adjuvant therapy in melanoma is associated with significant side effects, which necessitates evaluation of health-related quality of life (HRQOL). Our trial examined the HRQOL effects of adjuvant pegylated IFN-α-2b (PEG-IFN-α-2b) versus observation in patients with stage III melanoma. Methods A total of 1,256 patients with stage III melanoma were randomly assigned after full lymphadenectomy to receive either observation (n = 629) or PEG-IFN-α-2b (n = 627): induction 6 μg/kg/wk for 8 weeks then maintenance 3 μg/kg/wk for an intended total duration of 5 years. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 was used to assess HRQOL. Results At 3.8 years of median follow-up, for the primary end point, recurrence-free survival (RFS), risk was reduced by 18% (hazard rate = 0.82; P = .01) in the PEG-IFN-α-2b arm compared with observation. Significant and clinically meaningful differences occurred with the PEG-IFN-α-2b treatment arm compared with the observation group, showing decreased global HRQOL at month 3 (−11.6 points; 99% CI, −8.2 to −15.0) and year 2 (−10.5 points; 99% CI, −6.6 to −14.4). Many of the other scales showed statistically significant differences between scores when comparing the two arms. From a clinical point of view, important differences were found for five scales: two functioning scales (social and role functioning) and three symptom scales (appetite loss, fatigue, and dyspnea), with the PEG-IFN-α-2b arm being most impaired. Conclusion PEG-IFN-α-2b leads to a significant and sustained improvement in RFS. There is an expected negative effect on global HRQOL and selected symptoms when patients undergo PEG-IFN-α-2b treatment.