tbuckley/cabot-search huggingface dataset:
Nitric oxide measured with single-breath and tidal-breathing methods in asthma and COPD
Authors: SR Rutgers, RJ Meijer, HA Kerstjens, TW van der Mark, GH Koeter, DS Postma
Journal: European Respiratory Journal (1998)

Nitric oxide (NO) can be measured in exhaled air with the single-breath (SB) and tidal-breathing (TB) methods. To allow comparison between different laboratories, a European Respiratory Society task force recently reported guidelines for standardization of both methods. To facilitate comparison between laboratories further, this study investigated whether there is a difference between NO values measured with SB and TB methods in subjects with asthma or chronic obstructive pulmonary disease (COPD), and in healthy subjects. Moreover, the differences between groups were studied and the influence of smoking in asthma was assessed. Sixteen atopic nonsmoking asthmatics, 16 atopic currently smoking asthmatics, 16 nonatopic nonsmoking healthy controls, 16 nonatopic exsmokers with COPD and 16 nonatopic exsmoking healthy controls were studied. NO concentrations differed substantially between both methods. Mean NO concentrations were higher with the SB than with the TB method in nonsmoking and in smoking asthmatics and especially so with the higher NO values. Furthermore, NO values with both methods were higher in nonsmoking asthmatics than in nonsmoking healthy subjects. NO was not significantly different between exsmokers with COPD and healthy exsmokers. In conclusion nitric oxide values of the single-breath and tidal-breathing methods are not interchangeable. Both methods can be used to measure differences between groups.
Communicating the risk of injury in schoolboy rugby: using Poisson probability as an alternative presentation of the epidemiology
Authors: Nikesh Parekh, Stewart D Hodges, Allyson M Pollock, Graham Kirkwood
Journal: British Journal of Sports Medicine (2011)

The communication of injury risk in rugby and other sports is underdeveloped and parents, children and coaches need to be better informed about risk.A Poisson distribution was used to transform population based incidence of injury into average probabilities of injury to individual players.The incidence of injury in schoolboy rugby matches range from 7 to 129.8 injuries per 1000 player-hours; these rates translate to average probabilities of injury to a player of between 12% and 90% over a season.Incidence of injury and average probabilities of injury over a season should be published together in all future epidemiological studies on school rugby and other sports. More research is required on informing and communicating injury risks to parents, staff and children and how it affects monitoring, decision making and prevention strategies.
Clinical spectrum of adult bronchiolitis – An eleven years retrospective analysis
Authors: Paulo Matos, Daniela Madama, Maria João Matos, Lina Carvalho
Journal: European Respiratory Journal (2014)

Introduction: Bronchiolitis are a heterogeneous group of inflammatory diseases of the small airways, primary or secondary to other systemic diseases, but mostly with viral cause or associated with tobacco exposure. Regarding the difficulty of a specific diagnosis and the lack of literature in the subject, it is important to characterize this pathology.  Objective: To describe epidemiologic, functional and radiologic characteristics in patients with histologic diagnosis of bronchiolitis.  Materials and methods: Retrospective analysis through hospitalar data consultation of patients with histological diagnosis of bronchiolitis during the 2000-2011 period.  Results: 193 histological diagnoses of bronchiolitis were confirmed. Mean age was 48.72 (±17.16) with male predominance (69.4%). Respiratory co-morbiditie was the most frequent (28%). Histologicaly there was prevalence for Respiratory bronchiolitis (RB) (53.9%), Obliterative bronchiolitis (OB) (16.1%) and Constrictive bronchiolitis (CB) (11.4%). Chronic symptoms were present all histological types, less evident in RB (acute symptoms in 43.9%). Smooking was most related to RB (80.7%). The main radiologic finding in RB was pneumothorax (38.5%) and ground glass opacities in OB (32.1%) and CB (36.6%). Pulmonary nodules or masses were found in 22.3%, mainly associated with Folicular bronchiolitis (50%). Spirometry was normal in 69% and obstructive in 23.5% of patients.  Conclusions: The majority of diagnosis corresponded to secondary bronchiolitis associated with respiratory pathology, mainly due to tobacco abuse. Our study shows the importance to correlate the radiological and clinical features in order to obtain a definitive diagnosis.
Minimal Residual Disease Assessed by Multiparameter Flow Cytometry in Multiple Myeloma: Impact on Outcome in the Medical Research Council Myeloma IX Study
Authors: Andy C. Rawstron, J. Anthony Child, Ruth M. de Tute, Faith E. Davies, Walter M. Gregory, Sue E. Bell, Alexander J. Szubert, Nuria Navarro-Coy, Mark T. Drayson, Sylvia Feyler, Fiona M. Ross, Gordon Cook, Graham H. Jackson, Gareth J. Morgan, Roger G. Owen
Journal: Journal of Clinical Oncology (2013)

To investigate the prognostic value of minimal residual disease (MRD) assessment in patients with multiple myeloma treated in the MRC (Medical Research Council) Myeloma IX trial.Multiparameter flow cytometry (MFC) was used to assess MRD after induction therapy (n = 378) and at day 100 after autologous stem-cell transplantation (ASCT; n = 397) in intensive-pathway patients and at the end of induction therapy in non-intensive-pathway patients (n = 245).In intensive-pathway patients, absence of MRD at day 100 after ASCT was highly predictive of a favorable outcome (PFS, P < .001; OS, P = .0183). This outcome advantage was demonstrable in patients with favorable and adverse cytogenetics (PFS, P = .014 and P < .001, respectively) and in patients achieving immunofixation-negative complete response (CR; PFS, P = .0068). The effect of maintenance thalidomide was assessed, with the shortest PFS demonstrable in those MRD-positive patients who did not receive maintenance and longest in those who were MRD negative and did receive thalidomide (P < .001). Further analysis demonstrated that 28% of MRD-positive patients who received maintenance thalidomide became MRD negative. MRD assessment after induction therapy in the non-intensive-pathway patients did not seem to be predictive of outcome (PFS, P = .1).MRD assessment by MFC was predictive of overall outcome in patients with myeloma undergoing ASCT. This predictive value was seen in patients achieving conventional CR as well as patients with favorable and adverse cytogenetics. The effects of maintenance strategies can also be evaluated, and our data suggest that maintenance thalidomide can eradicate MRD in some patients.
Effects of Therapeutic Hypercapnia on Mesenteric Ischemia–Reperfusion Injury
Authors: John G. Laffey, Robert P. Jankov, Doreen Engelberts, A. Keith Tanswell, Martin Post, Thomas Lindsay, J. Brendan Mullen, Alex Romaschin, Derek Stephens, Colin McKerlie, Brian P. Kavanagh
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Hypercapnic acidosis protects against direct lung injury in in vivo and ex vivo models, however, lung injury/acute respiratory distress syndrome commonly occurs after a nonpulmonary etiology. We investigated whether therapeutic hypercapnia (TH)-deliberate elevation of carbon dioxide (CO2) tension-would protect against lung injury after splanchnic ischemia-reperfusion injury in an in vivo model. TH was associated with preservation of lung mechanics, attenuation of protein leakage, and improved oxygenation compared with control conditions. Lung protection was therapeutic as well as prophylactic. Protection was dose-dependent, but inspired CO2 concentrations above 5.0% were associated with little additional lung protection. Before lung injury, increasing FICO2 resulted in a dose-dependent increase in PaO2. Lung protection with hypercapnia occurred despite pulmonary artery pressures that were greater than observed with normocapnia. Reperfusion increased lipid peroxidation (tissue 8-isoprostane concentration) in the bowel, liver, and lung, and caused histologically apparent bowel injury; however, none of these effects was altered by TH. Therefore, TH-induced by adding CO2 to inspired gas-provides consistent protection against lung injury in terms of lung permeability, oxygenation, and lung mechanics after mesenteric ischemia-reperfusion. These data further support the emerging evidence for ongoing physiologic study of TH at the bedside.
The Molecular and Genetic Basis of Fibroblast Growth Factor Receptor 3 Disorders: The Achondroplasia Family of Skeletal Dysplasias, Muenke Craniosynostosis, and Crouzon Syndrome with Acanthosis Nigricans*
Authors: Zoltan Vajo, Clair A. Francomano, Douglas J. Wilkin
Journal: Endocrine Reviews (2000)

Abstract Achondroplasia, the most common form of short-limbed dwarfism in humans, occurs between 1 in 15,000 and 40,000 live births. More than 90% of cases are sporadic and there is, on average, an increased paternal age at the time of conception of affected individuals. More then 97% of persons with achondroplasia have a Gly380Arg mutation in the transmembrane domain of the fibroblast growth factor receptor (FGFR) 3 gene. Mutations in the FGFR3 gene also result in hypochondroplasia, the lethal thanatophoric dysplasias, the recently described SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) dysplasia, and two craniosynostosis disorders: Muenke coronal craniosynostosis and Crouzon syndrome with acanthosis nigricans. Recent evidence suggests that the phenotypic differences may be due to specific alleles with varying degrees of ligand-independent activation, allowing the receptor to be constitutively active. Since the Gly380Arg achondroplasia mutation was recognized, similar observations regarding the conserved nature of FGFR mutations and resulting phenotype have been made regarding other skeletal phenotypes, including hypochondroplasia, thanatophoric dysplasia, and Muenke coronal craniosynostosis. These specific genotype-phenotype correlations in the FGFR disorders seem to be unprecedented in the study of human disease. The explanation for this high degree of mutability at specific bases remains an intriguing question.
Antireceptor antibodies as probes of insulinlike growth factor receptor structure.
Authors: M Kasuga, N Sasaki, C R Kahn, S P Nissley, M M Rechler
Journal: Journal of Clinical Investigation (1983)

Insulin receptors and Type I insulinlike growth factor (IGF) receptors have a similar structure with a major binding subunit of Mr approximately 130,000 linked by disulfide bonds to other membrane proteins to form a Mr greater than 300,000 complex. Both insulin and Type I IGF receptors also interact with both insulin and IGF, although with different binding affinities. We used a panel of human and rabbit sera containing antibodies to insulin receptors to determine whether these sera also interact with Type I IGF receptors. Immunoglobulins from five of five human sera inhibited binding of 125I-insulin and 125I-IGF-I to insulin receptors and Type I IGF receptors in human placenta and human lymphocytes. The rank order of reactivity with both receptors was the same; two sera, however, appeared to be selectively less reactive with the Type I IGF receptor, especially in placenta. Sera from five of seven patients and from a rabbit immunized with purified insulin receptor effectively immunoprecipitated both placental insulin receptors and Type I IGF receptors. Of the remaining sera, one had only a low titer against the insulin receptor and did not immunoprecipitate the IGF receptor, whereas the second serum effectively immunoprecipitated cross-linked and surface-iodinated insulin receptors, but had negligible reactivity against the Type I IGF receptor. These results suggest that most antisera to the insulin receptor also contain antibodies to Type I IGF receptors. Whether both specificities are inherent in the same or different antibody molecules remains to be determined. These data support the hypothesis that the insulin and IGF-I receptors are separate but related molecules, although there remains a small possibility that both receptors are domains on the same protein.
Interleukin-2 induces profound reversible cholestasis: a detailed analysis in treated cancer patients.
Authors: B Fisher, A M Keenan, B S Garra, S M Steinberg, D E White, A M DiBisceglie, J H Hoofnagle, P Yolles, S A Rosenberg, M T Lotze
Journal: Journal of Clinical Oncology (1989)

Interleukin-2 (IL-2)-based immunotherapy is associated with profound reversible cholestasis and hyperbilirubinemia. We performed a nonrandomized retrospective and prospective analysis to determine the incidence, characteristics, clinical course, and nature of the IL-2-induced liver dysfunction in patients with cancer. Patients received IL-2 at a dose of 20,000 to 100,000 units (U)/kg thrice daily for up to 5 days. Fifty-one patients on adjuvant treatment protocols received a mean of 10.18 +/- 2.38 IL-2 doses and 11.67 +/- 4.16 doses were delivered to 210 patients with advanced disease during this period. Retrospective analysis of all patients receiving this therapy revealed increases in the following liver function tests expressed as median, 25th percentile, and 75th percentile (range): bilirubin (mg/dL) 4.5, 2.6, 6.5 (.4 to 38.5); alkaline phosphatase (U/L) 256, 179, 378 (56-1680); SGOT (U/L) 80, 52, 117 (18 to 483); SGPT (U/L) 91, 64, 132 (20-540); prothrombin time 13.4, 12.8, 14.5 (10.8 to 35.4); and albumin (g/dL) values decreased (trough) slightly 3.0, 2.8, 3.2 (2.3 to 3.8). Multiple regression analysis revealed several factors that were significantly associated with the increase in bilirubin when jointly considered (model P2 less than or equal to .001) including total IL-2 dosage, increase in creatinine, alkaline phosphatase, weight, and SGOT. Similar increases were noted in a prospectively evaluated group of 10 patients. A return to normal levels of bilirubin was noted within 5.6 days of stopping IL-2. Fasting serum cholylglycine increased from a mean of 32.3 +/- 1.6 to a peak of 1556.0 +/- 625.0 mg/mL. Although conventional ultrasound examinations were unrevealing, tissue ultrasound examinations revealed a mean scatterer spacing (MSS) increase compared to baseline of .10 +/- .04 (P less than .02) suggesting hepatic edema or an infiltrative process. Further, computerized hepatobiliary nuclear medicine scans revealed a delay in uptake (2.2 +/- 0.5 fold greater) and excretion (8.0 +/- 5.9 fold greater) of technetium-99m labeled disofenin. These findings support the development of profound reversible cholestasis as the primary basis for the elevated bilirubin in patients undergoing IL-2 treatment and may have implications for understanding the jaundice observed in some patients postoperatively as well as that associated with sepsis and other inflammatory disorders. Specifically, the release of IL-2 or the induction of other factors similarly induced by IL-2 may be responsible for these findings. Tissue ultrasound and computerized hepatobiliary scans provide additional noninvasive assessments of liver function and physiology.
Genetic Ablation of M3 Muscarinic Receptors Attenuates Murine Colon Epithelial Cell Proliferation and Neoplasia
Authors: Jean-Pierre Raufman, Roxana Samimi, Nirish Shah, Sandeep Khurana, Jasleen Shant, Cinthia Drachenberg, Guofeng Xie, Jürgen Wess, Kunrong Cheng
Journal: Cancer Research (2008)

Colon epithelial cells express and most colon cancers overexpress M(3) muscarinic receptors (M(3)R). In human colon cancer cells, post-M(3)R signaling stimulates proliferation. To explore the importance of M(3)R expression in vivo, we used the azoxymethane-induced colon neoplasia model. Mice treated with weekly i.p. injection of saline [10 wild-type (WT) mice] or azoxymethane (22 WT and 16 M(3)R(-/-) mice) for 6 weeks were euthanized at 20 weeks. At week 20, azoxymethane-treated WT mice weighed approximately 16% more than M(3)R(-/-) mice (33.4 grams +/- 1.0 grams versus 27.9 grams +/- 0.5 grams; mean +/- SE, P < 0.001). In azoxymethane-treated M(3)R(-/-) mice, cell proliferation (BrdUrd staining) was reduced 43% compared with azoxymethane-treated WT mice (P < 0.05). Whereas control mice (both WT and M(3)R(-/-)) had no colon tumors, azoxymethane-treated WT mice had 5.3 +/- 0.5 tumors per animal. Strikingly, azoxymethane-treated M(3)R(-/-) mice had only 3.2 +/- 0.3 tumors per mouse (P < 0.05), a 40% reduction. Tumor volume in azoxymethane-treated M(3)R(-/-) mice was reduced 60% compared with azoxymethane-treated WT mice (8.1 mm(3) +/- 1.5 mm(3) versus 20.3 mm(3) +/- 4.1 mm(3); P < 0.05). Compared with WT, fewer M(3)R(-/-) mice had adenomas (6% versus 36%; P = 0.05), and M(3)R(-/-) mice had fewer adenocarcinomas per mouse (0.6 +/- 0.1 versus 1.7 +/- 0.4; P < 0.05). Eleven of 22 WT but no M(3)R(-/-) mice had multiple adenocarcinomas (P < 0.001). Compared with WT, azoxymethane-treated M(3)R-deficient mice have attenuated epithelial cell proliferation, tumor number, and size. M(3)R and post-M(3)R signaling are novel therapeutic targets for colon cancer.
Consensus Statement on the Triage of Critically III Patients
Authors: Charles L. Sprung
Journal: JAMA (1994)

The demand for medical services such as critical care is likely to often exceed supply. In the setting of these constraining conditions, institutions and individual providers of critical care must use some moral framework for distributing the available resources efficiently and equitably. Guidelines are therefore provided for triage of critically ill patients. There are several general principles that should guide decision making: providers should advocate for patients; members of the provider team should collaborate; care must be restricted in an equitable system; decisions to give care should be based on expected benefit; mechanisms for alternative care should be planned; explicit policies should be written; prior public notification is necessary. Patients who are not expected to benefit from intensive care, such as those with imminently fatal illnesses or permanent unconsciousness, should not be placed in the intensive care unit. Hospitals should assign individuals the responsibility of intensive care triage, and a committee should oversee the performance of this responsibility to facilitate the most efficient and equitable use of intensive care.  ( JAMA . 1994;271:1200-1203)
A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study
Authors: Ilse Gijselinck, Tim Van Langenhove, Julie van der Zee, Kristel Sleegers, Stéphanie Philtjens, Gernot Kleinberger, Jonathan Janssens, Karolien Bettens, Caroline Van Cauwenberghe, Sandra Pereson, Sebastiaan Engelborghs, Anne Sieben, Peter De Jonghe, Rik Vandenberghe, Patrick Santens, Jan De Bleecker, Githa Maes, Veerle Bäumer, Lubina Dillen, Geert Joris, Ivy Cuijt, Ellen Corsmit, Ellen Elinck, Jasper Van Dongen, Steven Vermeulen, Marleen Van den Broeck, Carolien Vaerenberg, Maria Mattheijssens, Karin Peeters, Wim Robberecht, Patrick Cras, Jean-Jacques Martin, Peter P De Deyn, Marc Cruts, Christine Van Broeckhoven
Journal: The Lancet Neurology (2011)
Foxc2 Is a Common Mediator of Insulin and Transforming Growth Factor β Signaling to Regulate Plasminogen Activator Inhibitor Type I Gene Expression
Authors: Hideo Fujita, Myengmo Kang, Mesut Eren, Linda A. Gleaves, Douglas E. Vaughan, Tsutomu Kume
Journal: Circulation Research (2006)

Elevated plasma levels of plasminogen activator inhibitor type I (PAI-1), a significant risk factor of ischemic heart disease, are associated with insulin resistance in which insulin and transforming growth factor (TGF)-β play a pivotal role in regulating PAI-1 production. Forkhead transcription factor FOXC2 is an important regulator of insulin resistance. However, the underlying molecular mechanisms to link FOXC2 to PAI-1 levels in insulin resistance remain to be elucidated. Here, we demonstrate that Foxc2 is a common transcriptional activator of insulin and TGF-β signaling to directly regulate PAI-1 expression via 2 distinct target sites, an insulin response element (IRE) and a novel forkhead-binding element (FBE), adjacent to a Smad-binding site. We found that in adipocytes and endothelial cells Foxc2 mediates insulin action competing with another Forkhead protein, FOXO1, via the insulin response element, and simultaneously cooperate with the TGF-β/Smad pathway to transactivate PAI-1. Importantly, Foxc2 haploinsufficiency in mice significantly attenuates TGF-β1–induced PAI-1 expression in the cardiovascular system and adipose tissue. Taken together, we propose that Foxc2 is a key molecule to regulate PAI-1 gene expression.
ADRENAL STEROID INHIBITION OF VASOPRESSIN RELEASE FROM THE NEUROHYPOPHYSIS OF NORMAL SUBJECTS AND PATIENTS WITH ADDISON'S DISEASE *
Authors: Joseph F. Dingman, Rene H. Despointes
Journal: Journal of Clinical Investigation (1960)

1 Portions of these studies have been reported previ- ously (4-7).to 30 minute intervals by spontaneous voiding in 5 sub- jects and through an indwelling urethral catheter in 3.
Inference and Characterization of Horizontally Transferred Gene Families Using Stochastic Mapping
Authors: O. Cohen, T. Pupko
Journal: Molecular Biology and Evolution (2009)

Macrogenomic events, in which genes are gained and lost, play a pivotal evolutionary role in microbial evolution. Nevertheless, probabilistic-evolutionary models describing such events and methods for their robust inference are considerably less developed than existing methodologies for analyzing site-specific sequence evolution. Here, we present a novel method for the inference of gains and losses of gene families. First, we develop probabilistic-evolutionary models describing the dynamics of gene-family content, which are more biologically realistic than previously suggested models. In our likelihood-based models, gains and losses are represented by transitions between presence and absence, given an underlying phylogeny. We employ a mixture-model approach in which we allow both the gain rate and the loss rate to vary among gene families. Second, we use these models together with the analytic implementation of stochastic mapping to infer branch-specific events. Our novel methodology allows us to infer and quantify horizontal gene transfer (HGT) events. This enables us to rank various gene families and lineages according to their propensity to undergo gains and losses. Applying our methodology to 4,873 gene families shows that: 1) the novel mixture models describe the observed variability in gene-family content among microbes significantly better than previous models; 2) The stochastic mapping approach enables accurate inference of gain and loss events based on simulations; 3) At least 34% of the gene families analyzed are inferred to have experienced HGT at least once during their evolution; and 4) Gene families that were inferred to experience HGT are both enriched and depleted with respect to specific functional categories.
Age at initiation and frequency of screening to detect type 2 diabetes: a cost-effectiveness analysis
Authors: Richard Kahn, Peter Alperin, David Eddy, Knut Borch-Johnsen, John Buse, Justin Feigelman, Edward Gregg, Rury R Holman, M Sue Kirkman, Michael Stern, Jaakko Tuomilehto, Nick J Wareham
Journal: The Lancet (2010)