tbuckley/cabot-search huggingface dataset:
<i>N</i>-acetylcysteine reduces the risk of re-hospitalisation among patients with chronic obstructive pulmonary disease
Authors: C.M.J.M. Gerrits, R.M.C. Herings, H.G.M. Leufkens, J-W.J. Lammers
Journal: European Respiratory Journal (2003)

The aim of this study was to evaluate the effect of oral N-acetylcysteine in the prevention of re-hospitalisation for chronic obstructive pulmonary disease (COPD) exacerbations. Using the PHARmacoMOrbidity linkage (PHARMO) system the authors included all patients aged > or = 55 yrs who had been dispensed medication, labelled for respiratory indications (anatomical therapeutic chemical (ATC) classification system: R03), between 1986-1998 and who had also been hospitalised for COPD (International Classification of Diseases (ICD)-9: 491, 492, 496) in this time frame. These subjects were subsequently divided into two groups, those who had received N-acetylcysteine following discharge from their first admission between 1986-1998 and those who had not. All the patients were studied starting from their initial discharge, until their first readmission, death or end of data collection period. The maximum follow-up period was 1 yr. A total of 1,219 patients, who were hospitalised for COPD between 1986-1998, were included in this study. After adjustment for disease severity, it was observed that the use of N-acetylcysteine was significantly associated with a reduced risk of readmission. The readmission risk was significantly lower in patients with high average daily doses of N-acetylcysteine. In conclusion it was observed that N-acetylcysteine reduces the risk of rehospitalisation for chronic obstructive pulmonary disease by approximately 30% and that this risk reduction is dose-dependent.
Anti-tumour necrosis factor therapy for ankylosing spondylitis: international experience
Authors: J Braun, J Sieper, M Breban, E Collantes-Estevez, J Davis, R Inman, H Marzo-Ortega, H Mielants
Journal: Annals of the Rheumatic Diseases (2002)

The conventional approach to treatment of patients with spondyloarthritis (SpA), particularly ankylosing spondylitis (AS), has serious limitations, adding a sense of urgency to the evaluation of new treatments for these rheumatic disorders. Tumour necrosis factor α (TNFα) is a cytokine that has been shown to mediate inflammatory and regulatory activities in SpA and other immune mediated diseases, including other arthritides and inflammatory bowel disease. Positive results have been reported in several international open label and randomised controlled trials of infliximab and etanercept, the two main biological agents targeting TNFα, which have included approximately 300 patients with SpA. Specifically, TNFα-directed therapy resulted in significant improvements in disease activity, function, and quality of life in these patients, most of whom had AS and received infliximab. Preliminary evidence from open label, long term extension trials suggests clinical benefit with continued use. Serious side effects were rare and consistent with experience from patient groups receiving infliximab or etanercept treatment for inflammatory bowel disease or rheumatoid arthritis. Together, these findings herald an age of more effective treatment of patients with AS with anti-TNFα and other emerging biological agents.
Evolutionary Switch and Genetic Convergence on rbcL following the Evolution of C4 Photosynthesis
Authors: Pascal-Antoine Christin, Nicolas Salamin, A. Muthama Muasya, Eric H. Roalson, Flavien Russier, Guillaume Besnard
Journal: Molecular Biology and Evolution (2008)

Rubisco is responsible for the fixation of CO2 into organic compounds through photosynthesis and thus has a great agronomic importance. It is well established that this enzyme suffers from a slow catalysis, and its low specificity results into photorespiration, which is considered as an energy waste for the plant. However, natural variations exist, and some Rubisco lineages, such as in C4 plants, exhibit higher catalytic efficiencies coupled to lower specificities. These C4 kinetics could have evolved as an adaptation to the higher CO2 concentration present in C4 photosynthetic cells. In this study, using phylogenetic analyses on a large data set of C3 and C4 monocots, we showed that the rbcL gene, which encodes the large subunit of Rubisco, evolved under positive selection in independent C4 lineages. This confirms that selective pressures on Rubisco have been switched in C4 plants by the high CO2 environment prevailing in their photosynthetic cells. Eight rbcL codons evolving under positive selection in C4 clades were involved in parallel changes among the 23 independent monocot C4 lineages included in this study. These amino acids are potentially responsible for the C4 kinetics, and their identification opens new roads for human-directed Rubisco engineering. The introgression of C4-like high-efficiency Rubisco would strongly enhance C3 crop yields in the future CO2-enriched atmosphere.
Innate immunity against <i>Francisella tularensis</i> is dependent on the ASC/caspase-1 axis
Authors: Sanjeev Mariathasan, David S. Weiss, Vishva M. Dixit, Denise M. Monack
Journal: The Journal of Experimental Medicine (2005)

Francisella tularensis is a highly infectious gram-negative coccobacillus that causes the zoonosis tularemia. This bacterial pathogen causes a plague-like disease in humans after exposure to as few as 10 cells. Many of the mechanisms by which the innate immune system fights Francisella are unknown. Here we show that wild-type Francisella, which reach the cytosol, but not Francisella mutants that remain localized to the vacuole, induced a host defense response in macrophages, which is dependent on caspase-1 and the death-fold containing adaptor protein ASC. Caspase-1 and ASC signaling resulted in host cell death and the release of the proinflammatory cytokines interleukin (IL)-1β and IL-18. F. tularensis–infected caspase-1– and ASC-deficient mice showed markedly increased bacterial burdens and mortality as compared with wild-type mice, demonstrating a key role for caspase-1 and ASC in innate defense against infection by this pathogen.
Dietary Fiber Intake and Glycemic Index and Incidence of Diabetes in African-American and White Adults
Authors: June Stevens, Kyungmi Ahn, None Juhaeri, Denise Houston, Lyn Steffan, David Couper
Journal: Diabetes Care (2002)

OBJECTIVE—To determine the association of dietary fiber and glycemic index with incident type 2 diabetes in African-Americans and whites. RESEARCH DESIGN AND METHODS—We studied 12,251 adults aged 45–64 years and free of diabetes at baseline (1987–1989). A total of 1,447 cases of diabetes were reported between baseline and 9 years of follow-up. Diabetes status was determined by fasting glucose level ≥126 mg/dl (7.0 mmol/l), nonfasting glucose level ≥200 mg/dl (11.1 mmol/l), self-report of physician diagnosis, or use of diabetes medication. Usual dietary intake over the previous year was obtained at baseline using a 66-item food-frequency questionnaire. Nutrients were energy-adjusted using the residuals method. Proportional hazard regression analysis was used to examine dietary fiber intake and glycemic index as predictors of type 2 diabetes in both ethnic groups. RESULTS—After adjustment for age, BMI, education, smoking status, physical activity, sex, and field center, there were no statistically significant associations of intake of total dietary fiber, fruit fiber, legume fiber, glycemic index, or glycemic load with incident diabetes. The hazard ratio for the fifth compared with the first quintile of cereal fiber was 0.75 (95% CI 0.60–0.92) in whites and 0.86 (0.65–1.15) in African-Americans. CONCLUSIONS—This finding supports a protective role for cereal fiber in the development of diabetes in whites. More studies are needed to determine the role of dietary fiber and glycemic index in diabetes in African-Americans.
Truth About ERCC1 in Lung Cancer
Authors: Daniel S.-W. Tan, Quan-Sing Ng, Iain B.-H. Tan, Soon-Thye Lim, Wan-Teck Lim
Journal: Journal of Clinical Oncology (2010)

sion, as evaluated by immunohistochemistry, was associated with worse outcomes in inoperable non–small-cell lung cancer (NSCLC), particularly in men. However, like most previous literature pertaining to ERCC1 in NSCLC—the majority of which are retrospective in nature—there are methodological issues that require clarification. From the data presented, stage IIA, IIIA, and IIIB constitute 44% of the cohort. It is unclear from the survival analysis if stage was evenly distributed between groups, as well as the proportion of patients that were treated with curative intent— both of which have distinct prognostic implications. In addition, the use concurrent treatments, such as radiotherapy or gemcitabine and its known interaction with RRM1 expression, 2 can further influence outcome, confounding the interpretation of ERCC1 status on survival. Technical issues also require urgent resolution, especially pertaining to the measurement of ERCC1 expression with assays that are inadequately validated and have undefined thresholds of functional significance. Indeed, it can be challenging to equate expression levels of a single protein or mRNA transcript with repair capacity, which is a dynamic process comprising of interaction between multiple factors. 3 Moreover, the 8F1 antibody used for detection of ERCC1 in Holm et al 1 and other groups 4 has been shown to be by no means discriminatory. 5 In elegant validation experiments using formalinfixed, paraffin-embedded normal (negative control) and ERCC1XPF– deficient (positive control) cell lines, it was recently confirmed that 8F1 antibody was unable to differentiate between normal and ERCC1-deficient cells by immunohistochemistry. 6 In the same study, immunofluorescence experiments conducted on UV-C– damaged fibroblasts revealed diffuse cytoplasmic staining with the 8F1 antibody, as opposed to specific localization to the nucleus where DNA damage occurs. Nuclear-specific staining using alternative antibodies such as FL297 (anti-ERCC1) and 3F2 (anti-XPF) has subsequently been suggested to be more accurate in depicting DNA repair. 6
Serum thymulin in human zinc deficiency.
Authors: A S Prasad, S Meftah, J Abdallah, J Kaplan, G J Brewer, J F Bach, M Dardenne
Journal: Journal of Clinical Investigation (1988)

The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no overt clinical manifestations of zinc deficiency. The diagnosis of mild zinc deficiency was based on the assay of zinc in lymphocytes, granulocytes, and platelets. Serum thymulin activity was decreased as a result of mild zinc deficiency and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter was a sensitive indicator of zinc deficiency in humans. An increase in T101-, sIg-cells, decrease in T4+/T8+ ratio, and decreased IL 2 activity were observed in the experimental human model during the zinc depletion phase, all of which were corrected after repletion with zinc. Similar changes in lymphocyte subpopulation, correctable with zinc supplementation, were also observed in mildly ZD SCA subjects. Inasmuch as thymulin is known to induce intra- and extrathymic T cell differentiation, our studies provide a possible mechanism for the role of zinc on T cell functions.
Ductular reaction in hereditary hemochromatosis: The link between hepatocyte senescence and fibrosis progression
Authors: Marnie J. Wood, Victoria L. Gadd, Lawrie W. Powell, Grant A. Ramm, Andrew D. Clouston
Journal: Hepatology (2013)

The development of portal fibrosis following the iron loading of hepatocytes is the first stage of fibrogenesis in hereditary hemochromatosis. In other chronic liver diseases it has been shown that a ductular reaction (DR) appears early, correlates with fibrosis progression, and is a consequence of activation of an alternative pathway of hepatocyte replication. This study was designed to investigate the presence of the DR in hemochromatosis and describe its associations. Liver biopsies from 63 C282Y homozygous patients were assessed for hepatic iron concentration (HIC) and graded for iron loading, fibrosis stage, steatosis, and inflammation. Immunostaining allowed quantification of the DR, hepatocyte senescence and proliferation, and analysis incorporated clinical data. Hepatocyte senescence was positively correlated with HIC, serum ferritin, and oxidative stress. A DR was demonstrated and occurred prior to histological fibrosis. HIC, age, hepatocyte senescence and proliferation, portal inflammation, and excessive alcohol consumption all had significant associations with the extent of the DR. In multivariate analysis, iron loading, hepatocyte replicative arrest, and portal inflammation remained independently and significantly associated with the DR. Of factors associated with fibrosis progression, the DR (odds ratio [OR] 10.86 P &lt; 0.0001) and the presence of portal inflammation (OR 4.31, P = 0.028) remained significant after adjustment for cofactors. The extent of the DR regressed following therapeutic venesection. Conclusion : Iron loading of hepatocytes leads to impaired replication, stimulating the development of the DR in hemochromatosis and this correlates strongly with hepatic fibrosis. Portal inflammation occurs in hemochromatosis and is independently associated with the DR and fibrosis, and thus its role in this disease should be evaluated further. (HEPATOLOGY 2014;59:848–857)
Magnetosomes, Biogenic Magnetic Nanomaterials for Brain Molecular Imaging with 17.2 T MRI Scanner
Authors: Sébastien Mériaux, Marianne Boucher, Benjamin Marty, Yoann Lalatonne, Sandra Prévéral, Laurence Motte, Christopher T. Lefèvre, Françoise Geffroy, Franck Lethimonnier, Michel Péan, Daniel Garcia, Géraldine Adryanczyk‐Perrier, David Pignol, Nicolas Ginet
Journal: Advanced Healthcare Materials (2015)

The fast development of sensitive molecular diagnostic tools is currently paving the way for a personalized medicine. A new class of ultrasensitive magnetic resonance imaging (MRI) T 2 ‐contrast agents based on magnetosomes, magnetite nanocrystals biomineralized by magnetotactic bacteria, is proposed here. The contrast agents can be injected into the blood circulation and detected in the picomolar range. Purified magnetosomes are water‐dispersible and stable within physiological conditions and exhibit at 17.2 T a transverse relaxivity r 2 four times higher than commercial ferumoxide. The subsequent gain in sensitivity by T 2 * ‐weighted imaging at 17.2 T of the mouse brain vasculature is evidenced in vivo after tail vein injection of magnetosomes representing a low dose of iron (20 μmol iron kg −1 ), whereas no such phenomenon with the same dose of ferumoxide is observed. Preclinical studies of human pathologies in animal models will benefit from the combination of high magnetic field MRI with sensitive, low dose, easy‐to‐produce biocompatible contrast agents derived from bacterial magnetosomes.
Bacterial Biofilms Induce Neutrophil and B Cell Recruitment As Well As Up-regulation of IL-8 In Patients with Chronic Rhinosinusitis
Authors: J. Kofonow, A.M. Hekiert, L. Doghramji, D.W. Kennedy, A.G. Chiu, J.N. Palmer, N.A. Cohen
Journal: Journal of Allergy and Clinical Immunology (2009)
Cervical Spine in Psoriasis and in Psoriatic Arthritis
Authors: D. Kaplan, C. M. Plotz, L. Nathanson, L. Frank
Journal: Annals of the Rheumatic Diseases (1964)

We reported that both donor CD4<sup>+</sup> T and B cells in transplants were required for induction of an autoimmune-like chronic graft-versus-host disease (cGVHD) in a murine model of DBA/2 donor to BALB/c recipient, but mechanisms whereby donor B cells augment cGVHD pathogenesis remain unknown. In this study, we report that, although donor B cells have little impact on acute GVHD severity, they play an important role in augmenting the persistence of tissue damage in the acute and chronic GVHD overlapping target organs (i.e., skin and lung); they also markedly augment damage in a prototypical cGVHD target organ, the salivary gland. During cGVHD pathogenesis, donor B cells are activated by donor CD4<sup>+</sup> T cells to upregulate MHC II and costimulatory molecules. Acting as efficient APCs, donor B cells augment donor CD4<sup>+</sup> T clonal expansion, autoreactivity, IL-7Rα expression, and survival. These qualitative changes markedly augment donor CD4<sup>+</sup> T cells’ capacity in mediating autoimmune-like cGVHD, so that they mediate disease in the absence of donor B cells in secondary recipients. Therefore, a major mechanism whereby donor B cells augment cGVHD is through augmenting the clonal expansion, differentiation, and survival of pathogenic CD4<sup>+</sup> T cells.
Treatment of symptomatic patients with essential thrombocythemia: Effectiveness of anagrelide
Authors: Rossella R. Cacciola, Antonio Cipolla, Ernesto Di Francesco, Rosario Giustolisi, Emma Cacciola
Journal: American Journal of Hematology (2005)

Abstract We prospectively evaluated the effect of anagrelide (ANA) on platelets, PF4, F1+2, PAP, PAI‐1, and TFPI and erythromelalgia in patients with essential thrombocythemia (ET) receiving anti‐aggregants both pre‐ and post‐ANA. At first, we observed a successful reduction of platelets, which was associated with normalization of platelet coagulant and endothelial function and disappearance of erythromelalgia. Secondly, we found a correlation between PF4 and TFPI and between TFPI and thrombosis, suggesting that erythromelalgia may be caused by platelet‐mediated endothelial activation. These data may indicate that ANA may be efficacy in the treatment of symptomatic patients with ET. Am. J. Hematol. 80:81–83, 2005. © 2005 Wiley‐Liss, Inc.
Untreated Depression and Hippocampal Volume Loss
Authors: Yvette I. Sheline, Mokhtar H. Gado, Helena C. Kraemer
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The purpose of this study was to investigate the effect of antidepressant treatment on hippocampal volumes in patients with major depression. METHOD: For 38 female outpatients, the total time each had been in a depressive episode was divided into days during which the patient was receiving antidepressant medication and days during which no antidepressant treatment was received. Hippocampal gray matter volumes were determined by high resolution magnetic resonance imaging and unbiased stereological measurement. RESULTS: Longer durations during which depressive episodes went untreated with antidepressant medication were associated with reductions in hippocampal volume. There was no significant relationship between hippocampal volume loss and time depressed while taking antidepressant medication or with lifetime exposure to antidepressants. CONCLUSIONS: Antidepressants may have a neuroprotective effect during depression.
Guidelines for the management of actinic keratoses
Authors: D. de Berker, J.M. McGregor, B.R. Hughes
Journal: British Journal of Dermatology (2007)

These guidelines stemmed from a consensus meeting held by the British Photobiology Group (BPG) in 1999. Following this meeting one of the authors (J.M.M.) was invited to draw up guidelines for the management of actinic keratoses by the British Association of Dermatologists Therapy Guidelines and Audit Subcommittee. Relevant evidence was sought using the search terms 'solar keratosis' and 'actinic keratosis' in Medline from 1966 onwards. Additional and earlier literature was reviewed on the basis of references within post-1966 publications. All articles of apparent relevance were reviewed independently of the nature of the publication. The quality of the evidence elicited has been indicated. The National Ambulatory Medical Care Survey (U.S.A.) was used for further data on topical chemotherapy. Papers were reviewed and discussed by the contributors to the BPG Workshop (see Acknowledgments). Recommendations are evidence based where possible. Strength of recommendation is coupled with quality of evidence. Strength of recommendation includes consideration of apparent cost-benefit and practical considerations. Quality of evidence reflects the nature of the trial structure that provides data of efficacy.
Cigarette smoke inhalation and the acute airway response.
Authors: T Higenbottam, C Feyeraband, T J Clark
Journal: Thorax (1980)

The acute airway response to smoking varying numbers (one to four) of identical cigarettes in rapid succession and smoking single cigarettes of differing tar/nicotine yields was assessed repeatedly in 13 healthy smokers. The airway response was variable, indicating airway narrowing consistently in only three subjects. There appeared no difference between forced spirometry and measurement of airway resistance in detecting the airway response. No relationship was observed between the airway response and amount of smoke inhaled into the lungs as measured either by changes in venous blood nicotine or percentage carboxyhaemoglobin. When five smokers inhaled smoke directly from a cigarette acute airway narrowing was consistently observed. A normal smoking pattern consisting of an initial drag of smoke into the mouth, followed after a pause by inhalation of smoke diluted with air, did not consistently cause airway narrowing although similar amounts of smoke as the direct drag were inhaled as assessed by changes in venous blood nicotine. The manner of smoke inhalation affects the relative concentrations of the different constituents of smoke reaching the lungs and also appears to be the main determinant of the acute airway response to smoking, which was unrelated to the number of cigarettes smoked or the tar content of the smoke. This suggests that patterns of smoke inhalation may influence the pathogenesis of bronchial disease associated with smoking.