tbuckley/cabot-search huggingface dataset:
Increased expression of inducible nitric oxide synthase and cyclo-oxygenase-2 in the airway epithelium of asthmatic subjects and regulation by corticosteroid treatment
Authors: A E Redington
Journal: Thorax (2001)

<h3>BACKGROUND</h3> Nitric oxide (NO) and prostanoids are mediators of vascular and bronchial tone that are postulated to be involved in asthma. Increased levels of both are found in asthmatic subjects and are synthesised by enzymes that have cytokine inducible forms: inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX-2), respectively. We hypothesised that the in vivo expression of iNOS and COX-2 in the airways would be increased in asthma, and that these cytokine inducible enzymes may represent targets for regulation by corticosteroid treatment. <h3>METHODS</h3> Bronchial biopsy specimens were obtained from three groups of subjects: atopic asthmatics treated with β<sub>2</sub> agonists alone (n=7), atopic asthmatics additionally receiving regular treatment with corticosteroids (n=8), and non-asthmatic control subjects (n=10). Expression of iNOS and COX-2 mRNA and immunoreactive protein was studied using in situ hybridisation and quantitative immunohistochemistry. <h3>RESULTS</h3> Immunoreactivity and the hybridisation signal for iNOS and COX-2 were mainly localised in the airway epithelium. The proportion of epithelium immunostained was significantly greater in the non-steroid treated asthmatic subjects (iNOS 8.6 (1.8)%; COX-2 26.3 (4.6)%) than either the steroid treated asthmatics (iNOS 3.4 (1.0)%, p=0.009; COX-2 13.0 (0.6)%, p=0.0015) or the non-asthmatic controls (iNOS 4.2 (0.9)%, p=0.018; COX-2 11.6 (0.6)%, p=0.0003). Similarly, the hybridisation signal was stronger in the non-steroid treated group of asthmatic subjects than in the other two groups. <h3>CONCLUSIONS</h3> These findings highlight the potential role of the airway epithelium both as a contributor to the inflammatory process in asthma and as a target for inhaled corticosteroid treatment in this disease.
Nocturnal Asthma and the Importance of Race/Ethnicity and Genetic Ancestry
Authors: Albert M. Levin, Yun Wang, Karen E. Wells, Badri Padhukasahasram, James J. Yang, Esteban G. Burchard, L. Keoki Williams
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Nocturnal asthma is a common presentation and is associated with a more severe form of the disease. However, there are few epidemiologic studies of nocturnal asthma, particularly in minority populations.To identify factors associated with nocturnal asthma, including the contribution of self-identified race/ethnicity and genetic ancestry.The analysis included individuals from the Study for Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) cohort. Nocturnal asthma symptoms were assessed by questionnaire. Genome-wide genotype data were used to estimate genetic ancestry in a subset of African American participants. Logistic regression was used evaluate the association of various factors with nocturnal asthma, such as self-identified race/ethnicity and genetic ancestry.The study comprised 3,380 African American and 1,818 European Americans individuals with asthma. After adjusting for other potential explanatory variables, including controller medication use, African Americans were more than twice as likely (odds ratio, 2.56; 95% confidence interval, 2.24-2.93) to report nocturnal asthma when compared with European American individuals. Among the subset of African American participants with genome-wide genotype data (n = 1,040), estimated proportion of African ancestry was also associated with an increased risk of nocturnal asthma (P = 0.007). Differences in lung function explained a small, but statistically significant (P = 0.02), proportion of the relationship between genetic ancestry and nocturnal asthma symptoms.Both self-identified race/ethnicity and African ancestry appear to be independent predictors of nocturnal asthma. The mechanism by which genetic ancestry contributes to population-level differences in nocturnal asthma appears to be largely independent of lung function.
Low back pain and other overuse injuries in a group of Japanese triathletes.
Authors: J S Manninen, M Kallinen
Journal: British Journal of Sports Medicine (1996)

OBJECTIVE: To document the incidence of low back pain and other overuse injuries in a group of triathletes, and to investigate any associations with various physical and triathlon related factors. METHODS: By means of a questionnaire, the physical characteristics, training habits, and the incidences of overuse injuries of 92 Japanese triathletes (70 males, 22 females) were documented. Student's t and chi 2 tests were used to determine the significance of any associations with injury incidence, as well as differences between subjects experiencing or not experiencing low back pain in the previous year. RESULTS: Low back pain was experienced by 32% of subjects in the previous year. The majority (54%) of low back pain episodes lasted under seven days, suggesting mainly soft tissue involvement, and 19% lasted over three months, suggesting involvement of the intervertebral discs. Weekly trunk flexor muscle training frequency was significantly greater (P = 0.035) for the low back pain subjects. Close to significant differences for average weekly cycling time, trunk flexor muscle training time, and low intensity aerobic training, as well near significant associations for weight training and average weekly triathlon training load, were also found. No other factors were significantly associated with low back pain. Low back injuries accounted for 28% of all injuries. Only the knee was a more common single site of injury (33%). CONCLUSIONS: The three most common injuries suffered by the triathletes were of the knee, back and shoulder. The low back pain suffered by many triathletes could be of a potentially serious nature. It is suggested that cycling is a major risk factor for low back pain in triathletes.
Comparison of Medical Admissions to Intensive Care Units in the United States and United Kingdom
Authors: Hannah Wunsch, Derek C. Angus, David A. Harrison, Walter T. Linde-Zwirble, Kathryn M. Rowan
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: The United States has seven times as many intensive care unit (ICU) beds per capita as the United Kingdom; the effect on care of critically ill patients is unknown.Objectives: To compare medical ICU admissions in the United States and United Kingdom.Methods: Retrospective (2002–2004) cohort study of 172,785 ICU admissions (137 United States ICUs, Project IMPACT database; 160 United Kingdom ICUs, Case Mix Program) with patients followed until initial hospital discharge.Measurement and Main Results: United Kingdom (vs. United States) admissions were less likely to be admitted directly from the emergency room (ER) (33.4% vs. 58%); had longer hospital stays before ICU admission (mean days 2.6 ± 8.2 vs. 1 ± 3.6); and fewer were greater than or equal to 85 years (3.2% vs. 7.8%). United Kingdom patients were more frequently mechanically ventilated within 24 hours after ICU admission (68% vs. 27.4%); were sicker (mean Acute Physiology Score 16.7 ± 7.6 vs. 10.6 ± 6.8); and had higher primary hospital mortality (38% vs. 15.9%; adjusted odds ratio, 1.73; 95% confidence interval, 1.50–1.99). There was no mortality difference for mechanically ventilated patients admitted from the ER (adjusted odds ratio, 1.09; 95% confidence interval, 0.89–1.33). Comparisons of hospital mortality were confounded by differences in case mix; hospital length of stay (United Kingdom median 10 d [interquartile range {IQR}, 3–24] vs. United States 6 d [IQR, 3–11]; and discharge practices (more United States patients were discharged to skilled care facilities [29% of survivors vs. 6% in the United Kingdom]).Conclusions: Lower United Kingdom ICU bed availability is associated with fewer direct admissions from the ER, longer hospital stays before ICU admission, and higher severity of illness. Interpretation of between-country hospital outcomes is confounded by differences in case mix, processes of care, and discharge practices.
Both Patient and Facility Contribute to Achieving the Centers for Medicare and Medicaid Services' Pay-for-Performance Target for Dialysis Adequacy
Authors: Navdeep Tangri, Hocine Tighiouart, Klemens B. Meyer, Dana C. Miskulin
Journal: Journal of the American Society of Nephrology (2011)

The Centers for Medicare and Medicaid Services (CMS) designated the achieved urea reduction ratio (URR) as a pay-for-performance measure, but to what extent this measure reflects patient characteristics and adherence instead of its intent to reflect facility performance is unknown. Here, we quantified the contributions of patient case-mix and adherence to the variability in achieving URR targets across dialysis facilities. We found that 92% of 10,069 hemodialysis patients treated at 173 facilities during the last quarter of 2004 achieved the target URR ≥65%. Mixed-effect models with random intercept for dialysis facility revealed a significant facility effect: 11.5% of the variation in achievement of target URR was attributable to the facility level. Adjusting for patient case-mix reduced the proportion of variation attributable to the facility level to 6.7%. Patient gender, body surface area, dialysis access, and adherence with treatment strongly associated with achievement of the URR target. We could not identify specific facility characteristics that explained the remaining variation between facilities. These data suggest that if adherence is not a modifiable patient characteristic, providers could be unfairly penalized for caring for these patients under current CMS policy. These penalties may have unintended consequences.
Lineage-specific T-cell reconstitution following in vivo CD4+ and CD8+ lymphocyte depletion in nonhuman primates
Authors: Jessica C. Engram, Barbara Cervasi, Jose A. M. Borghans, Nichole R. Klatt, Shari N. Gordon, Ann Chahroudi, James G. Else, Robert S. Mittler, Donald L. Sodora, Rob J. de Boer, Jason M. Brenchley, Guido Silvestri, Mirko Paiardini
Journal: Blood (2010)
Antiangiogenic and Antitumor Effects of Bevacizumab in Patients With Inflammatory and Locally Advanced Breast Cancer
Authors: Suparna Bonthala Wedam, Jennifer A. Low, Sherry X. Yang, Catherine K. Chow, Peter Choyke, David Danforth, Stephen M. Hewitt, Arlene Berman, Seth M. Steinberg, David J. Liewehr, Jonathan Plehn, Arpi Doshi, Dave Thomasson, Nicole McCarthy, Hartmut Koeppen, Mark Sherman, JoAnne Zujewski, Kevin Camphausen, Helen Chen, Sandra M. Swain
Journal: Journal of Clinical Oncology (2006)

Purpose Vascular endothelial growth factor (VEGF) is a potent molecule that mediates tumor angiogenesis primarily through VEGF receptor 2 (VEGFR2). Bevacizumab, a recombinant humanized monoclonal antibody to VEGF, was administered to previously untreated patients to evaluate parameters of angiogenesis. Patients and Methods Twenty-one patients with inflammatory and locally advanced breast cancer were treated with bevacizumab for cycle 1 (15 mg/kg on day 1) followed by six cycles of bevacizumab with doxorubicin (50 mg/m 2 ) and docetaxel (75 mg/m 2 ) every 3 weeks. After locoregional therapy, patients received eight cycles of bevacizumab alone, and hormonal therapy when indicated. Tumor biopsies and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were obtained at baseline, and after cycles 1, 4, and 7. Results A median decrease of 66.7% in phosphorylated VEGFR2 (Y951) in tumor cells (P = .004) and median increase of 128.9% in tumor apoptosis (P = .0008) were seen after bevacizumab alone. These changes persisted with the addition of chemotherapy. There were no significant changes in microvessel density or VEGF-A expression. On DCE-MRI, parameters reflecting reduced angiogenesis, a median decrease of 34.4% in the inflow transfer rate constant (P = .003), 15.0% in the backflow extravascular- extracellular rate constant (P = .0007) and 14.3% in extravascular-extracellular volume fraction (P = .002) were seen after bevacizumab alone. Conclusion Bevacizumab has inhibitory effects on VEGF receptor activation and vascular permeability, and induces apoptosis in tumor cells.
Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options
Authors: Gerhard J Molderings, Stefan Brettner, Jürgen Homann, Lawrence B Afrin
Journal: Journal of Hematology & Oncology (2011)

Mast cell activation disease comprises disorders characterized by accumulation of genetically altered mast cells and/or abnormal release of these cells' mediators, affecting functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing. In most cases of mast cell activation disease, diagnosis is possible by relatively non-invasive investigation. Effective therapy often consists simply of antihistamines and mast cell membrane-stabilising compounds supplemented with medications targeted at specific symptoms and complications. Mast cell activation disease is now appreciated to likely be considerably prevalent and thus should be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity or patients in whom a definitively diagnosed major illness does not well account for the entirety of the patient's presentation.
Microfibrillar-associated protein 4 modulates airway smooth muscle cell phenotype in experimental asthma
Authors: Bartosz Pilecki, Anders Schlosser, Helle Wulf-Johansson, Thomas Trian, Jesper B Moeller, Niels Marcussen, Juan A Aguilar-Pimentel, Martin Hrabe de Angelis, Jorgen Vestbo, Patrick Berger, Uffe Holmskov, Grith L Sorensen
Journal: Thorax (2015)

<h3>Background</h3> Recently, several proteins of the extracellular matrix have been characterised as active contributors to allergic airway disease. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein abundant in the lung, whose biological functions remain poorly understood. In the current study we investigated the role of MFAP4 in experimental allergic asthma. <h3>Methods</h3> MFAP4-deficient mice were subjected to alum/ovalbumin and house dust mite induced models of allergic airway disease. In addition, human healthy and asthmatic primary bronchial smooth muscle cell cultures were used to evaluate MFAP4-dependent airway smooth muscle responses. <h3>Results</h3> MFAP4 deficiency attenuated classical hallmarks of asthma, such as eosinophilic inflammation, eotaxin production, airway remodelling and hyperresponsiveness. In wild-type mice, serum MFAP4 was increased after disease development and correlated with local eotaxin levels. MFAP4 was expressed in human bronchial smooth muscle cells and its expression was upregulated in asthmatic cells. Regarding the underlying mechanism, we showed that MFAP4 interacted with integrin αvβ5 and promoted asthmatic bronchial smooth muscle cell proliferation and CCL11 release dependent on phosphatidyloinositol-3-kinase but not extracellular signal-regulated kinase pathway. <h3>Conclusions</h3> MFAP4 promoted the development of asthmatic airway disease in vivo and pro-asthmatic functions of bronchial smooth muscle cells in vitro. Collectively, our results identify MFAP4 as a novel contributor to experimental asthma, acting through modulation of airway smooth muscle cells.
Long-Term Balancing Selection at the Blood Group-Related Gene B4galnt2 in the Genus Mus (Rodentia; Muridae)
Authors: Miriam Linnenbrink, Jill M. Johnsen, Inka Montero, Christine R. Brzezinski, Bettina Harr, John F. Baines
Journal: Molecular Biology and Evolution (2011)

Recent surveys of the human genome have highlighted the significance of balancing selection in relation to understanding the evolutionary origins of disease-associated variation. Cis-regulatory variation at the blood group–related glycosyltransferase B4galnt2 is associated with a phenotype in mice that closely resembles a common human bleeding disorder, von Willebrand disease. In this study, we have performed a survey of the 5′ flanking region of the B4galnt2 gene in several Mus musculus subspecies and Mus spretus. Our results reveal a clear pattern of trans-species polymorphism and indicate that allele classes conferring alternative tissue-specific expression patterns have been maintained for >2.8 My in the genus Mus. Furthermore, analysis of B4galnt2 expression patterns revealed the presence of an additional functional class of alleles, supporting a role for gastrointestinal phenotypes in the long-term maintenance of expression variation at this gene.
Therapeutic Clonotypic Vaccines
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (1992)

In this issue of the Journal, Kwak et al.1 give us a progress report concerning their work on the vaccination of patients with lymphoma against their own cancerous cells. In doing so, the authors illustrate a principle with potentially broad therapeutic applications. My purpose here is to explain the principle and indicate how it might be exploited in the treatment of a variety of diseases.The principle depends on the structural features of the variable region of an antibody, the portion of the molecule that binds antigen. This part of the antibody consists of two polypeptides, the heavy and . . .
The effect of hypoxia on the regional distribution of cardiac output in the dog.
Authors: H Adachi, W Strauss, H Ochi, H N Wagner
Journal: Circulation Research (1976)

Twenty-one dogs were studied under conditions of normal oxygenation and hypoxia with the microsphere distribution method to determine the effect of arterial oxygen saturation on the regional distribution of cardiac output. The dogs were anesthetized and artifically ventilated. Cannulas were placed in the left ventricle to administer microspheres and in a peripheral artery to determine cardiac output. Each dog received two microsphere injections: (1) while normally oxygenated (room air), and (2) under hypoxia (10% oxygen-90% nitrogen in 10 dogs and 5% oxygen-95% nitrogen in 11 dogs). Absolute cardiac output increased from 87 +/- 15 ml/min per kg to 101 +/- 14 ml/min per kg during mild hypoxia (10% oxygen) (P less than 0.05), and from 73 +/- 17 ml/min per kg to 120 +/- 24 ml/min per kg during severe hypoxia (5% oxygen) (P less than 0.01). Absolute blood flows increased to all organs except skin and muscle during hypoxia, although there were decreases in the fractional distribution of cardiac output to the splanchnic bed and kidney. Striking changes were found in coronary, hepatic, and cerebral circulation, and the organ with, greatest response to hypoxia was the heart, with increased coronary flow of 37% and 285% during exposure to 10% and 5% oxygen, respectively. Hence, low oxygen levels in blood cause redistribution of cardiac output and arterial content plays an important role in blood flow regulation.
Costimulation couture: a designer approach to regulating autoimmunity
Authors: M. J. Ansari
Journal: Journal of Clinical Investigation (2006)

Negative or inhibitory costimulatory pathways regulate T cell activation and play a role in peripheral tolerance. Targeting these pathways harnesses the physiologic mechanisms of regulating autoimmunity and could prove beneficial for the therapy of autoimmune diseases. However, attempts at targeting these pathways have been fraught with difficulties. In this issue of the JCI, Fife et al. describe a creative approach for targeting CTL-associated antigen 4 (CTLA-4) on activated T cells via genetically engineered B cells to prevent autoimmune diabetes in the NOD mouse (see the related article beginning on page 2252). Novel "designer" strategies targeting negative costimulatory pathways provide reasons for optimism in the search for a cure for devastating autoimmune diseases.
Eradication of methicillin resistant <i>Staphylococcus aureus</i> by “ring fencing” of elective orthopaedic beds
Authors: Leela C Biant, E Louise Teare, William W Williams, Jeremy D Tuite
Journal: BMJ (2004)

<b>Problem:</b> Deep infection after joint arthroplasty can be catastrophic, leading to further surgery, loss of the prosthesis, disability, and risk of mortality. Twenty nine new cases of methicillin resistant Staphylococcus aureus occurred in the first year after elective orthopaedic surgery was centralised to a district general hospital in Essex. <b>Design:</b> Prospective trial to establish whether ring fencing of elective orthopaedic beds and introduction of simple infection control measures has an effect on the rates of postoperative infections and number of patients treated. <b>Participants and setting:</b> All patients undergoing primary hip or knee replacement in a district general hospital in Essex, England, between July 1999 and July 2001. <b>Main measures for improvement:</b> Number of patients having joint replacement; number of all postoperative infections in the participant group; number of cases of methicillin resistant <i>Staphylococcus aureus</i>. <b>Strategies for change:</b> Ring fencing of the elective orthopaedic ward and introduction of simple infection control measures. <b>Effects of change:</b> The incidence of all postoperative infections decreased from 43/417 to 15/488 (P &lt; 0.0001), with no new cases of methicillin resistant <i>Staphylococcus aureus</i>. <b>Lessons learnt:</b> The introduction of a ring fenced elective orthopaedic ward and simple infection control measures allowed 17% more patients to be treated and significantly reduced the incidence of all postoperative infections.
New disinfecting apparatus for gastrointestinal fibre-endoscopes.
Authors: H J O'Connor, J Rothwell, S Maxwell, C Lincoln, A T Axon
Journal: Gut (1982)

Bacterial contamination of gastrointestinal fibre-endoscopes is a potential source of clinically significant infection. Aqueous 2% alkaline glutaraldehyde adequately disinfects fibre-endoscopes but may cause serious sensitivity reactions among endoscopy staff. A new 9closed-system9 disinfecting apparatus is described that disinfects with glutaraldehyde for 30 minutes before an endoscopy session, for two minutes between patient procedures, and for 10 minutes before storage. Bacteriological cultures of the endoscope after disinfection were virtually sterile. Extremely low glutaraldehyde vapour levels were detected by gas chromatography in endoscopy room air during disinfection procedures. This relatively simple apparatus offers rapid, effective, and safe disinfection of fibre-endoscopes.
Immunological consequences of thalidomide treatment in Sjogren's syndrome
Authors: N M Moutsopoulos
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To study the immunological consequences of systemic thalidomide treatment in patients with Sjögren's syndrome. <b>Methods:</b> Cytokine (tumour necrosis factor α (TNFα), interleukin (IL) 6) and soluble receptor (sIL2R) levels were measured in patient and control plasma (n = 7), before and after thalidomide treatment. Peripheral blood mononuclear cells were examined by FACS analysis for potential changes in specific cell populations (T cells, B cells, monocytes), and for the expression of activation markers (CD25, HLA-DR), costimulatory molecules (CD40, CD40L), TNF receptors, chemokine receptors, and adhesion molecules (l-selectin (l-sel)). <b>Results:</b> Owing to adverse effects of thalidomide, the treatment interval was limited. None the less, statistically significant changes in markers of cell activation were recorded in the four treated patients. Before treatment, HLA-DR, TNFRI, CXCRI, and CXCRII were raised in the patients compared with healthy controls (p&lt;0.05) and their expression was down regulated after treatment. B cell numbers and expression of the adhesion molecule l-sel also declined with thalidomide. <b>Conclusion:</b> Significant changes in measures of cell activation were detected during thalidomide treatment within this limited study, which upon further investigation may offer insight into the underlying immunoregulatory pathways of thalidomide.