6,020 research outputs found
A new look at the pathogenesis of asthma
No full textAsthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappointing and most therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms. With the disappointing outcomes of targeting individual Th-2 cytokines or manipulating T-cells, the time has come to re-evaluate the direction of research in this disease. A case is made that asthma has its origins in the airways themselves involving defective structural and functional behaviour of the epithelium in relation to environmental insults. Specifically, a defect in barrier function and an impaired innate immune response to viral infection may provide the substrate upon which allergic sensitization takes place. Once sensitized, the repeated allergen exposure will lead to disease persistence. These mechanisms could also be used to explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by respiratory viruses, air pollution episodes and exposure to biologically active allergens. Variable activation of this epithelial-mesenchymal trophic unit could also lead to the emergence of different asthma phenotypes and a more targeted approach to the treatment of these. It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established.<br/
Repeated high-dose inhalation allergen challenge in asthma
No full textIntroduction:? Inhalation allergen challenge in humans is used to investigate lung pathophysiology and responses to novel therapies. However, the single high-dose allergen challenges that are commonly performed do not mimic repeated symptomatic environmental allergen exposure.Objectives:? To develop and evaluate the safety of a repeated high-dose symptomatic inhalation allergen challenge model.Methods:? Sixteen subjects with atopic asthma were recruited. Each underwent three inhalation allergen challenges using house dust mite (Dermatophagoides pteronyssinus) antigen at 48-h intervals with a target of symptom induction and an early asthmatic reaction fall in forced expiratory volume in 1 s (FEV1) of 15% from baseline.Results:? All of the subjects completed the three-challenge protocol and the target immediate airway bronchoconstrictor response was achieved in all the subjects at all challenges. There were no adverse events recorded. The early asthmatic reaction was similar for the three challenges whether measured as mean maximal fall in FEV1 or mean area under the curve. The late asthmatic reaction was also similar over the three challenges with no evidence of priming or desensitisation. Symptom scores and reliever medication use significantly increased over the time of the challenges. Baseline lung function and reversibility was unchanged 4 days after the last challenge.Conclusion:? We demonstrate that repeated high-dose inhaled house dust mite allergen challenge in human volunteers with mild asthma is safe, repeatable and acceptable. This allows the use of this model in further studies focused on understanding the pathophysiology of allergen induced asthma and the impact of therapeutic interventions.<br/
Airway inflammation in atopic patients: a comparison of the upper and lower airways
No full textObjective. The purpose of this study was to understand and assess the inflammatory response within the upper and lower airways in patients suffering from both asthma and allergic rhinitis. Study Design. Cross-sectional study. Setting. A laboratory-based study of patients with allergic rhinitis and asthma. Subjects and Methods. Glycol methacrylate resin-embedded specimens from 10 patients with allergic rhinitis and asthma taken from the nose and bronchi were assessed by immunohistochemistry. Monoclonal antibodies directed against specific cell markers for mast cells (AA1), eosinophils (EG2), neutrophils (NOE), and lymphocytes (CD3(+), CD4(+), CD8(+)) were studied. Cells were counted blind (as cells/mm(2)) in the submucosal matrix. Mann-Whitney U test was used for analyses. P values of .05 or lower were considered statistically significant. Results. There was a significant increase in CD4(+) (P = .05) and CD8(+) cell counts (P = .001) in the lower airway compared to the upper airway. There were no differences between the 2 groups in the number of neutrophils, mast cells, eosinophils, and the CD3(+) cell counts. Conclusion. The upper and lower airways have parallel inflammation with possible bidirectional extension of inflammation in patients suffering from asthma and allergic rhinitis. There is increased lymphocytic infiltration in the lower airway, suggesting a possible preponderance for development and maintenance of allergic disease in the lower airway
Author\u27s Response to Children and Nature: Psychological, Sociocultural, and Evolutionary Investigations: Children and Nature – and Technology by Peter H. Kahn, Jr.
No full textAuthor\u27s Response to Children and Nature: Psychological, Sociocultural, and Evolutionary Investigations: Children and Nature – and Technology by Peter H. Kahn, Jr
Analysis of allergen immunotherapy studies shows increased clinical efficacy in highly symptomatic patients
No full textBackground: the assessment of allergen immunotherapy (AIT) efficacy in the treatment for seasonal allergic rhinoconjunctivitis (SAR) symptoms is challenging. Allergen immunotherapy differs from symptomatic therapy in that while symptomatic therapy treats patients after symptoms appear and aims to reduce symptoms, AIT is administered before symptoms are present and aims to prevent them. Thus, clinical studies of AIT can neither establish baseline symptom levels nor limit the enrolment of patients to those with the most severe symptoms. Allergen immunotherapy treatment effects are therefore diluted by patients with low symptoms for a particular pollen season. The objective of this analysis was to assess the effect possible to achieve with AIT in the groups of patients presenting the most severe allergic symptoms.Methods: study centres were grouped into tertiles categorized according to symptom severity scores observed in the placebo patients in each centre (low, middle and high tertiles). The difference observed in the average score in each tertile in active vs placebo-treated patients was assessed. This allowed an estimation of the efficacy that could be achieved in patients from sites where symptoms were high during the pollen season.Results: an increased treatment effect was observed in the most severe patients and was independent of the study analysed and symptom score used.Conclusions: the use of a tertile approach to analyse efficacy in AIT in SAR clinical studies can give a more accurate assessment of potential clinical benefi
Peter H. Amann Collection 1909-2009
No full textThis collection contains the personal and professional papers of Peter Amann, mostly correspondence but also including family papers, personal and professional writings, publicity materials relating to Peter Amann’s wife, and other personal documents. These materials reflect his role as a professor, author and prominent American historian as well as providing information about the rest of his family, including his father Paul Amann.Although most of these files date from his adult life, when he worked as a professor of history at various American universities, many files, including all of Series I, appear to have been inherited from his mother Dora Amann (née Iranyi) during the 1980s. These files include Dora Amann’s family papers and document the lives of the Iranyi/Israel family at the period before the Anschluss, during wartime, when Dora and Paul Amann lived in Paris, and conditions of Jewish individuals and families in Vienna under the Nazi regime.Other materials inherited from Dora Amann consist of some of Paul Amann’s correspondence, which contains a limited amount of post-war correspondence with prominent literary figures like Christopher Isherwood, Albert Camus, and the estate of Romain Rolland, and correspondence between Ernst Amann and his parents Dora and Paul. Included with the Paul Amann materials is an unpublished memoir, written in English, pertaining to his time as an Austrian soldier during World War I.The earlier family correspondence is almost entirely comprised of letters exchanged between Peter Amann and his parents. Starting in the mid 1950s, other figures begin to appear in the family correspondence, including Peter’s half-brother Wilhelm (Willi), who settled in Scotland, and Peter’s sister Eva. After the death of Paul Amann in 1959, the family correspondence contains an increasing amount of letters to and from Dora Amann.The professional correspondence starts during Peter Amann’s graduate studies at the University of Chicago in the 1950s. This series consists of correspondence and application materials for scholarships and fellowships, such as the Fulbright Peter Amann received in 1963, letters exchanged with colleagues and with collaborators on various research and book projects, letters seeking job placement, and letters with scholarly and academic publishers, relating both to proposed and to actual book and research projects. A substantial amount of official correspondence with the administrations of the various universities for which Amann worked, especially the University of Michigan, is also present. Additional materials in this series include diplomas and awards dating from Amann’s high school years in the 1940s through the 1970s, and various writings both academic and fictional, publications, and translations. Many of these writings included in the collection have never been published. A final subseries of professional correspondence pertains to his wife Enne Amann’s career as a folk singer, for which Peter Amann acted as manager during the mid 1960s through the early 1970s.The final series, personal correspondence, comprises letters and cards exchanged with friends and neighbors, as well as many materials pertaining to personal accommodations, such as lodging and transportation, while abroad for research purposes. The line between personal and professional correspondence is often blurry in the case of letters exchanged with professional colleagues, and therefore many correspondents appear in both the personal and professional series. The original order of the files with regards to dividing personal and professional correspondence was largely kept intact to avoid any destruction of contextual evidence. A variety of other types of correspondence, including letters to newspaper Op-Ed pages and letters to Congressional representatives expressing personal political views, were also included in this series, even if they refer to Peter Amann’s professional credentials.Peter Amann was born in 1927 in the Penzig district of Vienna, Austria. In 1939 Peter Amann fled with his family to France, and eventually reached New York via Portugal in 1941. After a few itinerant years following their arrival in the United States, Peter Amann graduated high school in Ohio and then continued his education at Oberlin College. In 1947 he completed his studies at Oberlin College and married Enne Niemi in Kentucky.For the next half decade Amann worked various jobs and wrote fiction in New York City and Milwaukee, before settling in Chicago in 1952 to work on a Ph.D. in History at the University of Chicago. Soon afterwards his first child Paula was born, and two other children, Sandra and David, were born within the following 7 years. Aside from an initial stint at Bowdoin College in Maine (1956-1959) and a few years on the faculty of the State University of New York Binghamton (1965-1968), Amann spent his entire professional career at various campuses of the University of Michigan. From 1971-2004 he was a Professor Emeritus of History at the Ann Arbor campus.Peter Amann is arguably most noted for his major work Revolution and Mass Democracy: The Paris Club Movement in 1848, but he also authored several other well-regarded scholarly books and articles on a variety of topics covering both European and American history. He has been awarded a Fulbright fellowship (1963-1964), a Guggenheim fellowship (1963-1964), and National Endowment for the Humanities fellowship (1982); for all of these awards he traveled to France for research.Dora Amann, née Israel, was born in 1894 in Vienna. Along with her immediate family, she converted to Protestantism and changed her name to Iranyi; her extended family kept the name Israel. She received a musical education in Vienna, Uppsala (Sweden), and Norway, and sang professionally. She married Paul Amann, a translator, with whom she had two children, Peter and Eva (later Eva Irrera). In 1939 she emigrated to France and then in 1941 to the United States. After Paul Amann’s death, she spent much of her life in New Paltz, New York, and died in 1993 near Washington, D.C.For a detailed biography of Peter Amann’s father, Paul Amann, please see the Peter Amann Collection, AR 3305.digitize
Finding Aid for the Peter H. Taylor Collection (MUM00442)
No full textThe collection contains papers, photographs, and audio recordings related to the life and work of author Peter H. Taylor
Evaluation of a rapid lateral flow immunoassay for Staphylococcus aureus detection in respiratory samples
No full textRapid point-of-care pathogen detection remains a challenge in routine diagnostics. A Staphylococcus aureus-specific lateral flow immunochromatography (LFI) test has been developed using a specific monoclonal antibody to the S. aureus cell-wall peptidoglycan. The LFI test was shown to be specific for S. aureus with no signal development for other Staphylococcal species or common respiratory pathogens. Evaluation of S. aureus isolates spiked into induced sputum and bronchoalveolar lavage samples derived from severe asthmatic patients showed a detection limit of 10(6) CFU/mL for the LFI. The test was also shown to successfully detect S. aureus in 1 sample independently determined to be S. aureus positive by quantitative polymerase chain reaction. The ability of the LFI test to rapidly detect S. aureus in clinical respiratory samples suggests that it might be a useful platform for further development of point-of-care diagnostic applications
Comparison of several author indices for gauging academic productivity
No full textBackground
Many author indices exist to gauge academic productivity. Several of these indices are calculated based upon an author's scholarly publication record, but the measurement methodology to calculate each index varies considerably, and the precise function being used, as well as the end result, is often complex and difficult to assess.
Method
Two straightforward methods to weigh author productivity from the publication and citation record were evaluated as possible means for providing a clearer assessment of scholarly activity. The author characteristic index (termed c-index) assigns author rank for each publication based upon author position. The characteristic prime (c') -index normalizes author rank from author position, so that the total weight per publication is unity. The top 10 scholars with keyword 'celiac disease' in the Google Scholar database were then assessed using these metrics. Rankings according to total number of publications, h-index, and c- and c'-indices were compared, then tabulated along with total papers included for assessment, and mean values per paper for author position, number of authors, citations, and year of publication.
Results
The order of the top ten authors with keyword 'celiac disease' varied substantially depending upon whether the h-index, c-index, or c'-index was used as a gauge. The characteristic indices assign credit to authors according to their position in an author list. The affiliated metrics provided a more complete picture of scholarly activity.
Conclusions
Academic achievement by scholars, based upon quantitative publication characteristics, has recently become of interest for evaluating job candidates, for determining work performance, and for bestowing awards and honors. The characteristic indices as described herein are readily calculated and interpreted, and may improve the assessment of scholarly activity
Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response
No full textRhinovirus (RV) infection is a major cause of asthma exacerbations which may be due to a deficient innate immune response in the bronchial epithelium. We hypothesized that the pleiotropic cytokine, TGF-?, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-?(2) increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-? antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-?(2) levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-? on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-? and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-? contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3
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