tbuckley/cabot-search huggingface dataset:
Different disease subtypes in allergic eosinophilic granulomatosis with polyangiitis (EGPA)
Authors: Manuela Latorre, Federica Novelli, Chiara Baldini, Elena Bacci, Veronica Seccia, Silvana Cianchetti, Stefano Bombardieri, Pier Luigi Paggiaro
Journal: European Respiratory Journal (2013)

Background: EGPA is a systemic disease in which we can distinguish “vasculitic” and “eosinophilic” manifestations.  Aims: to describe, in a group of EGPA patients, the occurrence of “vasculitic” and “eosinophilic” manifestations; to compare asthma in patients with a predominant “vasculitic phenotype” (VP) and an “eosinophilic phenotype” (EP).  Methods: 36 patients with EGPA were enrolled. Were assessed: lung function, bronchial hyperreactivity, asthma severity and control according to GINA guidelines and ACT test; sputum eosinophilia, exhaled nitric oxide (eNO) and blood biomarkers (eosinophilic count, serum IL-2-4-5, eosinophil cationic protein, anti-neutrophil cytoplasmic autoantibody (ANCA). Systemic and inhaled therapy, Birmingham Vasculitis Activity Score, Vasculitis Damage Index and the Asthma Quality of Life Questionnaire (AQLQ) were recorded.  Results: 19 patient with VP and 17 with EP were enrolled. Patients with VP were older (p  No significant differences were observed in lung function, asthma control, disease relapses, therapeutic approaches and quality of life.  Conclusions: This study confirms the presence of two different pathogenetic and clinical subsets in EGPA shedding a new light for targeted therapies.
Health-Related Quality Of Life Of Japanese Patients With Primary Immunodeficiency Diseases Receiving IgPro20, a 20% Liquid Subcutaneous Immunoglobulin (Hizentra®)
Authors: Hirokazu Kanegane, Kohsuke Imai, Masafumi Yamada, Hidetoshi Takada, Tadashi Ariga, Ataru Igarashi, Kiichiro Tsutani, Martin Bexon, Mikhail Rojavin, Midori Kobayashi, John-Philip Lawo, Art Zbrozek, Shigeaki Nonoyama, Toshiro Hara, Toshio Miyawaki
Journal: Journal of Allergy and Clinical Immunology (2014)
Response: Re: Rituximab Maintenance for the Treatment of Patients With Follicular Lymphoma: Systematic Review and Meta-analysis of Randomized trials
Authors: Liat Vidal, Anat Gafter-Gvili, Leonard Leibovici, Martin Dreyling, Michele Ghielmini, Ofer Shpilberg
Journal: JNCI Journal of the National Cancer Institute (2009)
How the new taekwondo rules have decreased the injuries and concussions since 2008
Authors: Paul Viscogliosi
Journal: British Journal of Sports Medicine (2013)

Before 2008, the rules of taekwondo to score points required powerful feet or hand movements to the trunk and feet movements to the head. Under this system the insurance statistics (Statistics of Mutuelle des Sports France) showed that taekwondo was a safe sport and that concussion was rare. The rules were changed 2 years ago with the adoption of an electronic scoring system for the trunk hits and valid head scoring with light feet taps only (without power). The electronic trunk protector's scoring system scores relative power in relation to the weight category. Statistics from three competitions that took place during 2011 and 2012 were analysed including the World Taekwondo Federation (WTF) World championships, the WTF World qualification tournament for the Olympic Games and the European Qualification tournament for Olympic Games and then compared to an earlier WTF World qualification tournament for Olympics Games ruled by the previous rule system (2008). Under the old system, we determined that out of 380 fights analysed, 55 injuries occurred, 3 were knocked down; which equates to 14.5% injuries and 0.8% KO. Under the new rules, we found that out of 1180 fights, there were 15 injuries and 2 knock down; which equates to 1.3% injuries and 0.17% KO. Conclusion With the new rules, the injuries were 11 times less likely to occur and the KOs 5 times less likely to occur. The next step for 2016 is to adopt an electronic headgear to make the sport of taekwondo even safer.
Exposure to Mycotoxins Increases the Allergic Immune Response in a Murine Asthma Model
Authors: Nicole Schütze, Irina Lehmann, Ulrike Bönisch, Jan C. Simon, Tobias Polte
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Epidemiological studies have shown that indoor molds are associated with increased prevalence and exacerbation of respiratory symptoms and asthma. Mycotoxins, secondary metabolites of molds, may contribute to these effects.To investigate the adjuvant activity of mycotoxins on allergic airway inflammation.Balb/c mice were exposed via the airways to gliotoxin and via the intestine to patulin, sensitized with ovalbumin (OVA), and then analyzed in acute and chronic murine asthma models. In addition, the effect of mycotoxin exposure on dendritic cell (DC) function was investigated using murine bone marrow-derived DCs.Exposure of mice to both mycotoxins enhanced dose-dependently airway hyperreactivity, eosinophilic lung inflammation, and OVA-specific IgE serum levels compared with mice that received only the antigen. These findings correlated with increased Th2 cytokine levels and decreased IFN-gamma production. Long-term mycotoxin exposure exacerbated chronic airway inflammation and airway remodeling. In vitro or in vivo mycotoxin exposure inhibited IL-12 production in maturing DCs and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. Mycotoxin exposure enhanced OVA-induced lung lipid peroxidation and moderately increased isoprostane levels in naive mice. Treatment of mycotoxin-exposed DCs with the antioxidants N-acetylcysteine or glutathione ethyl ester restored IL-12 secretion and pretreatment of exposed mice with N-acetylcysteine prevented the mycotoxin-induced increase of airway inflammation and AHR.Our results demonstrate that gliotoxin and patulin increase the allergic immune response in mice by modulating the Th1/Th2 balance via direct effects on IL-12 secretion in DCs and by inducing oxidative stress.
Prevalence of asthma and exhaled nitric oxide are increased in bleachery workers exposed to ozone
Authors: A-C. Olin, E. Andersson, M. Andersson, G. Granung, S. Hagberg, K. Torén
Journal: European Respiratory Journal (2003)

The aims of the present study were to determine whether exposure to high peaks of ozone resulted in an increased prevalence of asthma or respiratory symptoms among bleachery workers and whether nitric oxide (NO) was elevated in the exhaled air of these workers. Bleachery workers (n=228) from three Swedish pulp mills who had been exposed to ozone, together with 63 unexposed control subjects, were investigated by means of spirometry, Phadiatop®, exhaled and nasal NO and answers to a questionnaire concerning respiratory symptoms and exposure. Exposure to an ozone peak that gave rise to respiratory symptoms was defined as a “gassing”. Bleachery workers reporting four or more gassings involving ozone had an increased prevalence of adult-onset asthma, wheeze, and current asthma symptoms. They also had a higher median concentration of exhaled NO in comparison with those who reported no such gassings (19.2 versus 15.7 parts per billion). No such associations were found in respect of nasal NO. The results from this study show that bleachery workers who have been repeatedly exposed to ozone gassings have an increased prevalence of adult-onset asthma. The results also indicate exhaled nitric oxide may be a marker of airway inflammation in bleachery workers who have been exposed to high peaks of ozone.
SERMs: Meeting the Promise of Multifunctional Medicines
Authors: V. C. Jordan
Journal: JNCI Journal of the National Cancer Institute (2007)

The successful development and clinical evaluation of the selective estrogen receptor modulators in the Study of Tamoxifen and Raloxifene trial provides an occasion to reflect on the milestone that has been achieved and the potential for further progress in the chemoprevention of breast cancer. The evolution of tamoxifen from a successful treatment for breast cancer to the first chemopreventive for any cancer took two decades. Clinicians gained an enormous amount of experience with the use of tamoxifen as a treatment, and, as a result, there were few surprises in terms of efficacy or the side effect profile when the medicine was used to prevent breast cancer in high-risk women. In contrast, raloxifene emerged via the novel path of the evidence-based hypothesis that a drug targeted at one disease, osteoporosis, could also prevent breast cancer. Changes in health care strategies to implement chemoprevention take time, but the evidence now suggests that chemoprevention has become a reality in clinical practice.
T cell genetic background determines default T helper phenotype development in vitro.
Authors: C S Hsieh, S E Macatonia, A O'Garra, K M Murphy
Journal: The Journal of Experimental Medicine (1995)

A host's ability to resist certain pathogens such as Leishmania major can depend upon the phenotype of T helper (Th) subset that develops. Different murine genetic backgrounds are known to significantly alter the direction of Th subset development, although the cellular basis of this influence is poorly understood. To examine the basis of this effect we used an in vitro alpha/beta-T cell receptor (TCR) transgenic system for analysis of Th phenotype development. To control for TCR usage, we derived the DO11.10 alpha/beta-TCR transgene in several genetic backgrounds. Our findings suggest that the effects of genetic background on Th phenotype development reside within the T cell, and not the antigen-presenting cell compartment. Transgenic T cells from both the B10.D2 and BALB/c backgrounds showed development toward either the Th1 or Th2 phenotype under the strong directing influence of interleukin (IL) 12 and IL4, respectively. However, when T cells were activated in vitro under neutral conditions in which exogenous cytokines were not added, B10.D2-derived T cells acquired a significantly stronger Th1 phenotype than T cells from the BALB/c background, correspondent with in vivo Th responses to Leishmania in these strains. Importantly, these cytokine differences resulted in distinct functional properties, because B10.D2- but not BALB/c-derived T cells could induce macrophage production of nitric oxide, an important antimicrobial factor. Thus, the genetically determined default Th phenotype development observed in vitro may correspond to in vivo Th subset responses for pathogens such as Leishmania which do not initiate strong Th phenotype-directing signals.
Improving Postapproval Drug Safety Surveillance: Getting Better Information Sooner
Authors: Sean Hennessy, Brian L. Strom
Journal: The Annual Review of Pharmacology and Toxicology (2014)

Adverse drug events (ADEs) are an important public health concern, accounting for 5% of all hospital admissions and two-thirds of all complications occurring shortly after hospital discharge. There are often long delays between when a drug is approved and when serious ADEs are identified. Recent and ongoing advances in drug safety surveillance include the establishment of government-sponsored networks of population databases, the use of data mining approaches, and the formal integration of diverse sources of drug safety information. These advances promise to reduce delays in identifying drug-related risks and in providing reassurance about the absence of such risks.
Craniofacial profile in Asian and white subjects with obstructive sleep apnoea
Authors: B Lam
Journal: Thorax (2005)

<b>Background:</b> Clinical detection of structural narrowing of the upper airway may facilitate early recognition of obstructive sleep apnoea (OSA). To determine whether the craniofacial profile predicts the presence of OSA, the upper airway and craniofacial structure of 239 consecutive patients (164 Asian and 75 white subjects) referred to two sleep centres (Hong Kong and Vancouver) were prospectively examined for suspected sleep disordered breathing. <b>Methods:</b> All subjects underwent a history and physical examination with measurements of anthropometric parameters and craniofacial structure including neck circumference, thyromental distance, thyromental angle, and Mallampati oropharyngeal score. OSA was defined as an apnoea-hypopnoea index (AHI) of ⩾5/hour on full overnight polysomnography. <b>Results:</b> Discriminant function analysis indicated that the Mallampati score (F = 0.70), thyromental angle (F = 0.60), neck circumference (F = 0.54), body mass index (F = 0.53), and age (F = 0.53) were the best predictors of OSA. After controlling for ethnicity, body mass index and neck circumference, patients with OSA were older, had larger thyromental angles, and higher Mallampati scores than non-apnoeic subjects. These variables remained significantly different between OSA patients and controls across a range of cut-off values of AHI from 5 to 30/hour. <b>Conclusions:</b> A crowded posterior oropharynx and a steep thyromental plane predict OSA across two different ethnic groups and varying degrees of obesity.
<i>Pseudomonas aeruginosa</i> Type-3 Secretion System Dampens Host Defense by Exploiting the NLRC4-coupled Inflammasome
Authors: Emmanuel Faure, Jean-Baptiste Mear, Karine Faure, Sylvain Normand, Aurélie Couturier-Maillard, Teddy Grandjean, Viviane Balloy, Bernhard Ryffel, Rodrigue Dessein, Michel Chignard, Catherine Uyttenhove, Benoit Guery, Philippe Gosset, Mathias Chamaillard, Eric Kipnis
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Pseudomonas aeruginosa, a major problem pathogen responsible for severe infections in critically ill patients, triggers, through a functional type-3 secretion system (T3SS), the activation of an intracellular cytosolic sensor of innate immunity, NLRC4. Although the NLRC4-inflammasome-dependent response contributes to increased clearance of intracellular pathogens, it seems that NLRC4 inflammasome activation decreases the clearance of P. aeruginosa, a mainly extracellular pathogen.We sought to determine the underlying mechanisms of this effect of the activation of NLRC4 by P. aeruginosa.We established acute lung injury in wild-type and Nlrc4(-/-) mice using sublethal intranasal inocula of P. aeruginosa strain CHA expressing or not a functional T3SS. We studied 96-hour survival, lung injury, bacterial clearance from the lungs, cytokine secretion in bronchoalveolar lavage, lung antimicrobial peptide expression by quantitative polymerase chain reaction, and flow cytometry analysis of lung cells.Nlrc4(-/-) mice showed enhanced bacterial clearance and decreased lung injury contributing to increased survival against extracellular P. aeruginosa strain expressing a functional T3SS. The mechanism involved decreased NLRC4-inflammasome-driven IL-18 secretion attenuating lung injury caused by excessive neutrophil recruitment. Additionally, in the lungs of Nlrc4(-/-) mice secretion of IL-17 by innate immune cells was increased and responsible for increased expression of lung epithelial antimicrobial peptides. Furthermore, IL-18 secretion was found to repress IL-17 and IL-17-driven lung antimicrobial peptide expression.We report a new role of the T3SS apparatus itself, independently of exotoxin translocation. Through NLRC4 inflammasome activation, the T3SS promotes IL-18 secretion, which dampens a beneficial IL-17-mediated antimicrobial host response.
IFN-γ Enhances the Antimyeloma Activity of the Fully Human Anti–Human Leukocyte Antigen-DR Monoclonal Antibody 1D09C3
Authors: Carmelo Carlo-Stella, Anna Guidetti, Massimo Di Nicola, Cristiana Lavazza, Loredana Cleris, Daniela Sia, Paolo Longoni, Marco Milanesi, Michele Magni, Zoltan Nagy, Paolo Corradini, Antonino Carbone, Franca Formelli, Alessandro M. Gianni
Journal: Cancer Research (2007)

To investigate the therapeutic activity of the fully human anti-HLA-DR antibody 1D09C3 in multiple myeloma (MM), we reevaluated HLA-DR expression on CD138(+) cells, analyzed the capacity of IFN-gamma to up-regulate HLA-DR expression on MM cell lines, and tested the in vitro and in vivo activity of 1D09C3 alone or in combination with IFN-gamma. CD138(+)HLA-DR(+) cells were detected in 31 of 60 patients, with 15 of 60 patients having >/=20% CD138(+)HLA-DR(+) cells (median, 50%; range, 23-100). Because primary plasma cells cannot be efficiently cultured in vitro, we used a panel of MM cell lines with a dim/negative to bright HLA-DR expression to evaluate 1D09C3-induced cell death. Annexin V/propidium iodide (PI) staining showed that 1D09C3-induced cell death correlated with constitutive HLA-DR expression. Induction of HLA-DR by IFN-gamma restored the sensitivity of HLA-DR dim cell lines to 1D09C3. In vivo, the combined IFN-gamma/1D09C3 treatment significantly increased the median survival of nonobese diabetic/severe combined immunodeficient mice xenografted with KMS-11 cell line, compared with controls (147 versus 48 days, P </= 0.0001) or mice receiving 1D09C3 alone (147 versus 92 days, P </= 0.03). The better therapeutic activity of IFN-gamma/1D09C3 treatment over 1D09C3 alone was further shown by a 2-fold increase of mice being disease-free at 150 days after xenograft (47% versus 25%). No mice experienced any apparent treatment-related toxicity. Our data show that (a) one fourth of MM patients express HLA-DR on CD138(+) cells and (b) IFN-gamma-induced up-regulation of HLA-DR results in a potent enhancement of the in vivo antimyeloma activity of 1D09C3.
The Reproducibility of Repeat Measures of Airway Inflammation in Stable Atopic Asthma
Authors: JOHN L. FAUL, ELIZABETH A. DEMERS, CONOR M. BURKE, LEONARD W. POULTER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Measures of airway inflammation are increasingly being used as outcome measures in asthma intervention studies. Meaningful interpretation of observed changes in bronchial mucosal cell numbers should depend, in part, on the reproducibility of repeat measures over time. We wanted to investigate the reproducibility of immunopathologic and physiologic parameters after short and long measurement intervals. We therefore performed spirometry, bronchial provocation challenge, and fiberoptic bronchoscopy with endobronchial biopsy (always right upper lobe second-generation bronchus) at baseline, after 2 wk, and again after 8 wk on nine subjects with stable atopic asthma (receiving inhaled placebo and beta-agonist therapy only). Numbers of T cells, memory T cells (CD45Ro(+)), macrophages (CD68(+)), and eosinophils (EG1(+) and EG2(+)) on immunohistochemical stains of bronchial biopsies were quantified by computerized image analysis. Intraclass correlation coefficients (ICCs) of reproducibility were calculated for repeat measures of each parameter and a high ICC (greater than 0.6) was interpreted as "highly reproducible." Repeat measures of FEV(1), FEF(25-75%), and PC(20) were highly reproducible after short (2-wk) and long (8-wk) intervals. Only repeat measures of EG2(+) had an ICC greater than 0.6 after 8 wk. Repeat measures of CD45Ro(+), EG2(+), and T cell numbers (but not CD68(+) and EG1(+) cells) are highly reproducible and reliable parameters of asthmatic airway inflammation after a 2 wk interval.
Cdc42-mediated MTOC polarization in dendritic cells controls targeted delivery of cytokines at the immune synapse
Authors: Julian Pulecio, Jelena Petrovic, Francesca Prete, Giulia Chiaruttini, Ana-Maria Lennon-Dumenil, Chantal Desdouets, Stephane Gasman, Oscar R. Burrone, Federica Benvenuti
Journal: The Journal of Experimental Medicine (2010)

The immune synapse (IS) forms as dendritic cells (DCs) and T cells interact in lymph nodes during initiation of adaptive immunity. Factors that contribute to the formation and maintenance of IS stability and function have been mostly studied in T cells, whereas little is known about events occurring during synapse formation in DCs. Here, we show that DCs activated by Toll-like receptor (TLR) agonists reorient the microtubule-organizing center (MTOC) toward the interacting T cell during antigen-specific synapse formation through a mechanism that depends on the Rho GTPase Cdc42. IL-12, a pivotal cytokine produced by DCs, is found enriched around the MTOC at early time points after TLR ligation and is dragged to the DC–T cell interface in antigen-specific synapses. Synaptic delivery of IL-12 induces activation of pSTAT4 and IFN-γ neosynthesis in CD8+ naive T cells engaged in antigen-specific conjugates and promotes the survival of antigen-primed T cells. We propose that DC polarization increases the local concentration of proinflammatory mediators at the IS and that this represents a new mechanism by which T cell priming is controlled.
Predictive value of BAL cellular analysis in differentiating pulmonary tuberculosis and sarcoidosis
Authors: S. Greco, A. Marruchella, M. Massari, C. Saltini
Journal: European Respiratory Journal (2005)

criteria were applied, the FeNO values were not more discriminative between children with and without asthma or atopy.With respect to the ambient nitric oxide values, we have examined their effect on exhaled nitric oxide.Since there was no significant influence of ambient nitric oxide levels ,20 ppb on the fraction of exhaled nitric oxide values in our study population (figs 2 and 3), we decided to include all children with ambient nitric oxide levels ,20 ppb in the analyses.When the analyses were repeated, including only those children for whom the ambient nitric oxide values were ,10 ppb, similar results were observed.
Incidence of serious injury and death during sport and recreation activities in Victoria, Australia
Authors: B J Gabbe, C F Finch, P A Cameron, O D Williamson
Journal: British Journal of Sports Medicine (2005)

Background: Participation in sport and recreation is widely encouraged for general good health and the prevention of some non-communicable diseases. However, injury is a significant barrier to participation, and safety concerns are a factor in the decision to participate. An understanding of the sport/recreation activities associated with serious injury is useful for informing physical activity choices and for setting priorities for the targeting of injury prevention efforts. Objectives: To describe the epidemiology of serious injuries sustained in sport/recreation activities by adults in Victoria, Australia. Methods: The Victorian State Trauma Registry and the National Coroner’s Information Service were used to identify and describe sport/recreation related serious injuries, including deaths, occurring during the period July 2001 to June 2003. Age adjusted rates of serious injury and death were calculated using participation figures for each sport and general population data. Results: There were 150 cases of serious injury and 48 deaths. The rates of serious injury and death were 1.8 and 0.6 per 100 000 participants per year respectively. Motor, power boat, and equestrian sports had the highest rates of serious injury. Most deaths were due to drowning. Conclusion: Although the risk of serious injury through sport/recreation participation is low, motor, power boat, and equestrian sports should be priorities for further research into injury prevention. Most sport/recreation related deaths are due to drowning, highlighting this area for prevention efforts.
Hypoglycaemia after initiation of treatment with etanercept in a patient with type 2 diabetes mellitus
Authors: E Bonilla, Y Y Lee, P E Phillips, A Perl
Journal: Annals of the Rheumatic Diseases (2007)

Etanercept, a dimeric fusion protein consisting of the extracellular portion of the human p75 tumour necrosis factor α (TNFα) receptor and the Fc receptor of human immunoglobulin G subclass 1, has been used for the treatment of a variety of rheumatological conditions such as rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis.1

We report the case of a 54 year old white woman with a longstanding history of RA and type 2 diabetes mellitus who developed episodes of hypoglycaemia after initiation of etanercept treatment. The episodes occurred only on …