tbuckley/cabot-search huggingface dataset:
The intermediate filament protein, vimentin, is a regulator of NOD2 activity
Authors: Craig Stevens, Paul Henderson, Elaine R Nimmo, Dinesh C Soares, Belgin Dogan, Kenneth W Simpson, Jeffrey C Barrett, David C Wilson, Jack Satsangi
Journal: Gut (2012)

<h3>Objective</h3> Mutations in the nucleotide-binding oligomerisation domain-containing protein 2 (NOD2) gene remain the strongest genetic determinants for Crohn9s disease (CD). Having previously identified vimentin as a novel NOD2-interacting protein, the authors aimed to investigate the regulatory effects of vimentin on NOD2 function and the association of variants in <i>Vim</i> with CD susceptibility. <h3>Design</h3> Coimmunoprecipitation, fluorescent microscopy and fractionation were used to confirm the interaction between NOD2 and vimentin. HEK293 cells stably expressing wild-type NOD2 or a NOD2 frameshift variant (L1007fs) and SW480 colonic epithelial cells were used alongside the vimentin inhibitor, withaferin A (WFA), to assess effects on NOD2 function using the nuclear factor-kappaB (NF-κB) reporter gene, green fluorescent protein-LC3-based autophagy, and bacterial gentamicin protection assays. International genome-wide association meta-analysis data were used to test for associations of single-nucleotide polymorphisms in <i>Vim</i> with CD susceptibility. <h3>Results</h3> The leucine-rich repeat domain of NOD2 contained the elements required for vimentin binding; CD-associated polymorphisms disrupted this interaction. NOD2 and vimentin colocalised at the cell plasma membrane, and cytosolic mislocalisation of the L1007fs and R702W variants correlated with an inability to interact with vimentin. Use of WFA demonstrated that vimentin was required for NOD2-dependent NF-κB activation and muramyl dipeptide-induced autophagy induction, and that NOD2 and vimentin regulated the invasion and survival properties of a CD-associated adherent-invasive <i>Escherichia coli</i> strain. Genetic analysis revealed an association signal across the haplotype block containing <i>Vim</i>. <h3>Conclusion</h3> Vimentin is an important regulator of NOD2 function and a potential novel therapeutic target in the treatment of CD. In addition, <i>Vim</i> is a candidate susceptibility gene for CD, supporting the functional data.
CD44posCD49fhiCD133/2hi Defines Xenograft-Initiating Cells in Estrogen Receptor–Negative Breast Cancer
Authors: Matthew J. Meyer, Jodie M. Fleming, Amy F. Lin, S. Amal Hussnain, Erika Ginsburg, Barbara K. Vonderhaar
Journal: Cancer Research (2010)

Defining the populations of tumor-initating cells that are present in tumors is a first step in developing therapeutics to target these cells. We show here that both CD44(pos)CD24(neg) and CD44(pos)CD24(pos) cell populations in estrogen receptor (ER) alpha-negative breast tumors are tumorigenic in murine xenograft models. We also describe a third population of xenograft-initiating cells (XIC) enriched in CD44(pos)CD49f(hi)CD133/2(hi) cells that display heightened tumorigenicity, self-renewal in vivo, and the capacity to give rise to functional and molecular heterogeneity. Consistent with their capacity for self-renewal, these cells express elevated levels of Sox2, Bmi-1, and/or Nanog and their CpG islands are hypermethylated relative to nontumorigenic cells. These differences in methylome regulation may be responsible for the dramatic functional differences between the two populations. The identification of CD44(pos)CD49f(hi)CD133/2(hi) XIC in ER-negative tumors may lead to expanded understanding of these tumors and ultimately the development of therapeutics designed to specifically target the cells.
Granulomatosis-associated common variable immunodeficiency disorder: a case-control study versus sarcoidosis
Authors: Diane Bouvry, Luc Mouthon, Pierre-Yves Brillet, Marianne Kambouchner, Jean-Pierre Ducroix, Vincent Cottin, Julien Haroche, Jean-Francois Viallard, Romain Lazor, François Lebargy, Abdellatif Tazi, Benoît Wallaert, Amar Smail, Jean-Luc Pellegrin, Hilario Nunes, Zahir Amoura, Jean-François Cordier, Dominique Valeyre, Jean-Marc Naccache
Journal: European Respiratory Journal (2012)

The aim of the present study was to investigate to what extent interstitial lung disease (ILD) in common variable immunodeficiency disorder (CVID)-associated granulomatous disease (GD) is similar to pulmonary sarcoidosis 20 patients with CVID/GD were included in a retrospective study conducted by the Groupe Sarcoïdose Francophone. Medical records were centralised. Patients were compared with 60 controls with sarcoidosis. Clinical examination showed more frequent crackles in patients than controls (45% versus 1.7%, respectively; p&lt;0.001). On thoracic computed tomography scans, nodules (often multiple and with smooth margins), air bronchograms and halo signs were more frequent in patients than controls (80% versus 42%, respectively; p=0.004) as well as bronchiectasis (65% versus 23%, respectively; p&lt;0.001). The micronodule distribution was perilymphatic in 100% of controls and in 42% of patients (p&lt;0.001). Bronchoalveolar lavage analysis showed lower T-cell CD4/CD8 ratios in patients than in controls (mean± sd 1.6±1.1 versus 5.3±4, respectively; p&lt;0.01). On pathological analysis, nodules and consolidations corresponded to granulomatous lesions with or without lymphocytic disorders in most cases. Mortality was higher in patients than controls (30% versus 0%, respectively) and resulted from common variable immunodeficiency complications. ILD in CVID/GD presents a specific clinical picture and evolution that are markedly different from those of sarcoidosis.
Biopsy validation of 18F-DOPA PET and biodistribution in gliomas for neurosurgical planning and radiotherapy target delineation: results of a prospective pilot study
Authors: D. H. Pafundi, N. N. Laack, R. S. Youland, I. F. Parney, V. J. Lowe, C. Giannini, B. J. Kemp, M. P. Grams, J. M. Morris, J. M. Hoover, L. S. Hu, J. N. Sarkaria, D. H. Brinkmann
Journal: Neuro-Oncology (2013)

Delineation of glioma extent for surgical or radiotherapy planning is routinely based on MRI. There is increasing awareness that contrast enhancement on T1-weighted images (T1-CE) may not reflect the entire extent of disease. The amino acid tracer (18)F-DOPA (3,4-dihydroxy-6-[18F] fluoro-l-phenylalanine) has a high tumor-to-background signal and high sensitivity for glioma imaging. This study compares (18)F-DOPA PET against conventional MRI for neurosurgical biopsy targeting, resection planning, and radiotherapy target volume delineation.Conventional MR and (18)F-DOPA PET/CT images were acquired in 10 patients with suspected malignant brain tumors. One to 3 biopsy locations per patient were chosen in regions of concordant and discordant (18)F-DOPA uptake and MR contrast enhancement. Histopathology was reviewed on 23 biopsies. (18)F-DOPA PET was quantified using standardized uptake values (SUV) and tumor-to-normal hemispheric tissue (T/N) ratios.Pathologic review confirmed glioma in 22 of 23 biopsy specimens. Thirteen of 16 high-grade biopsy specimens were obtained from regions of elevated (18)F-DOPA uptake, while T1-CE was present in only 6 of those 16 samples. Optimal (18)F-DOPA PET thresholds corresponding to high-grade disease based on histopathology were calculated as T/N > 2.0. In every patient, (18)F-DOPA uptake regions with T/N > 2.0 extended beyond T1-CE up to a maximum of 3.5 cm. SUV was found to correlate with grade and cellularity.(18)F-DOPA PET SUV(max) may more accurately identify regions of higher-grade/higher-density disease in patients with astrocytomas and will have utility in guiding stereotactic biopsy selection. Using SUV-based thresholds to define high-grade portions of disease may be valuable in delineating radiotherapy boost volumes.
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Authors: Deborah J. Hilton, Timothy A. Welborn, Peter K. O’Rourke, Christopher M. Reid
Journal: Diabetes Care (2002)

Comment -I interpret these results to support the recommendation of both the American Kidney Foundation and the American Diabetes Association that ACR can be used instead of a timed collection.Timed collections, 24 h or otherwise, are very inconvenient and often not collected accurately.Since albumin excretion is highly variable from day to day (up to 25%), a repeat ACR to fulfill the criterion of two of three positive values within a 3-to 6-month period as recommended for the diagnosis of microalbuminuria would very likely have reduced the false-positive rate of 6%.Mogensen CE: Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes.
Exhaled nitric oxide from lung periphery is increased in COPD
Authors: C. Brindicci, K. Ito, O. Resta, N. B. Pride, P. J. Barnes, S. A. Kharitonov
Journal: European Respiratory Journal (2005)

Single constant flow exhaled nitric oxide (eNO) cannot distinguish between the sources of NO. The present study measured eNO at multiple expired flows ( MEF eNO) to partition NO into alveolar (C alv,NO ) and bronchial (J aw,NO ) fractions to investigate peripheral lung contribution to eNO in chronic obstructive lung disease (COPD). MEF eNO were made in 81 subjects including 18 nonsmokers, 16 smokers and 47 COPD patients of different severity by the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD): 0 (n = 14), 1 (n = 7), 2 (n = 11), 3 (n = 8) and 4 (n = 7). COPD severity was correlated with an increased C alv,NO regardless of the patient's smoking habit or current treatment. The levels of C alv,NO (in ppb) were 1.4±0.09 in nonsmokers, 2.1±0.1 in smokers categorised as GOLD stage 0 (smokers-GOLD 0 ), 3.3±0.18 in GOLD 1–2 and 3.4±0.1 in GOLD 3–4 . J aw,NO levels (pL·s −1 ) were higher in nonsmokers than smokers-GOLD 0 (716.2±33.3 versus 464.7±41.8), GOLD 3–4 (609.4±71). Diffusion of NO in the airways ( D aw,NO pL·ppb −1 s −1 ) was higher (p&lt;0.05) in GOLD 3–4 than in nonsmokers (15±1.2 versus 11±0.5) and smokers-GOLD 0 (11.6±0.5). MEF eNO measurements were reproducible, free from day-to-day and diurnal variation and were not affected by bronchodilators. In conclusion, chronic obstructive pulmonary disease is associated with elevated alveolar nitric oxide. Measurements of nitric oxide at multiple expired flows may be useful in monitoring inflammation and progression of chronic obstructive pulmonary disease, and the response to anti-inflammatory treatment.
IgE-activated basophils regulate eosinophil tissue entry by modulating endothelial function
Authors: Laurence E. Cheng, Brandon M. Sullivan, Lizett E. Retana, Christopher D.C. Allen, Hong-Erh Liang, Richard M. Locksley
Journal: The Journal of Experimental Medicine (2015)

Vertebrate immunity has evolved a modular architecture in response to perturbations. Allergic inflammation represents such a module, with signature features of antigen-specific IgE and tissue eosinophilia, although the cellular and molecular circuitry coupling these responses remains unclear. Here, we use genetic and imaging approaches in models of IgE-dependent eosinophilic dermatitis to demonstrate a requisite role for basophils. After antigenic inflammation, basophils initiate transmigration like other granulocytes but, upon activation via their high-affinity IgE receptor, alter their migratory kinetics to persist at the endothelium. Prolonged basophil–endothelial interactions, in part dependent on activation of focal adhesion kinases, promote delivery of basophil-derived IL-4 to the endothelium and subsequent induction of endothelial vascular cell adhesion molecule-1 (VCAM-1), which is required for eosinophil accumulation. Thus, basophils are gatekeepers that link adaptive immunity with innate effector programs by altering access to tissue sites by activation-induced interactions with the endothelium.
High Glucose Stimulates Proliferation and Collagen Type I Synthesis in Renal Cortical Fibroblasts
Authors: DONG CHEOL HAN, MOTOHIDE ISONO, BRENDA B. HOFFMAN, FUAD N. ZIYADEH
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Renal tubular epithelial cells and interstitial fibroblasts are active participants in tubulointerstitial fibrosis, the best correlate of decreased glomerular filtration in diabetic nephropathy. It was reported previously that high ambient glucose stimulates transforming growth factor-β (TGF-β) mRNA and bioactivity, promotes cellular hypertrophy, and increases collagen synthesis in proximal tubular cells. This study evaluates the effects of high glucose and TGF-β on the behavior of murine renal cortical fibroblasts (TFB) in culture. High glucose (450 mg/dl) significantly increased [ 3 H]-thymidine incorporation (by 60 to 80% after 24 to 72 h) and cell number, without significantly increasing cell death when compared with normal glucose (100 mg/dl). There also was a transient increase in the mRNA of the c- myc and egr-1 early-response genes. Exogenous TGF-β1 was promitogenic rather than antiproliferative in contrast to other renal cell types. Northern blot analysis demonstrated constitutive expression of TGF-β1, -β2, and -β3 transcripts. Exposure to high glucose increased all three TGF-β isoforms in a time-dependent manner. High glucose as well as exogenous TGF-β1 also increased [ 3 H]-proline incorporation, α2(I) collagen mRNA, and type I collagen protein (measured by immunoassay). Treatment with a neutralizing pan-selective monoclonal anti-TGF-β antibody markedly attenuated the stimulation by high ambient glucose of thymidine incorporation, TGF-β1 mRNA, and type I collagen mRNA and protein levels. It is concluded that high ambient glucose and exogenous TGF-β1 share similar actions on renal fibroblasts. Moreover, the stimulation of cell proliferation and collagen type I synthesis in these cells by high ambient glucose are mediated by activation of an autocrine TGF-β system.
Quality of life, coach behaviour and competitive anxiety in Winter Youth Olympic Games participants
Authors: Larissa Ledochowski, Christine Unterrainer, Gerhard Ruedl, Martin Schnitzer, Martin Kopp
Journal: British Journal of Sports Medicine (2012)

Background To ensure the highest technical performance, speed, safety, excellent control and to improve competitive performance, a successful regulation of competitive anxiety is necessary. Therefore, it seems crucial to identify factors influencing competitive anxiety of adolescent athletes. Research suggests that people reporting high quality of life are more capable to cope with stressful and challenging situations than others. The aim of this study was to investigate the impact of quality of life, the involvement of parents in sports career and coach's leadership behaviour on competitive anxiety in Winter Youth Olympic Games participants. Methods During the first Winter Youth Olympic Games 2012 in Innsbruck/Austria, 662 (316 women) participants completed questionnaires and single items to assess quality of life, coach's leadership behaviour, parental involvement in sports career and competitive anxiety. Results Multiple regression analysis revealed positive influences of high quality of life and useful coach instruction on competitive anxiety. Conclusions The relationship between quality of life, coach behaviour and competitive anxiety in young elite athletes competing at the first Winter Youth Olympic Games should be considered in long-term programmes for reducing competitive stress.
Success Story of Targeted Therapy in Chronic Myeloid Leukemia: A Population-Based Study of Patients Diagnosed in Sweden From 1973 to 2008
Authors: Magnus Björkholm, Lotta Ohm, Sandra Eloranta, Åsa Derolf, Malin Hultcrantz, Jan Sjöberg, Therese Andersson, Martin Höglund, Johan Richter, Ola Landgren, Sigurdur Y. Kristinsson, Paul W. Dickman
Journal: Journal of Clinical Oncology (2011)

Purpose Chronic myeloid leukemia (CML) management changed dramatically with the development of imatinib mesylate (IM), the first tyrosine kinase inhibitor targeting the BCR-ABL1 oncoprotein. In Sweden, the drug was approved in November 2001. We report relative survival (RS) of patients with CML diagnosed during a 36-year period. Patients and Methods Using data from the population-based Swedish Cancer Registry and population life tables, we estimated RS for all patients diagnosed with CML from 1973 to 2008 (n = 3,173; 1,796 males and 1,377 females; median age, 62 years). Patients were categorized into five age groups and five calendar periods, the last being 2001 to 2008. Information on use of upfront IM was collected from the Swedish CML registry. Results Relative survival improved with each calendar period, with the greatest improvement between 1994-2000 and 2001-2008. Five-year cumulative relative survival ratios (95% Cls) were 0.21 (0.17 to 0.24) for patients diagnosed 1973-1979, 0.54 (0.50 to 0.58) for 1994-2000, and 0.80 (0.75 to 0.83) for 2001-2008. This improvement was confined to patients younger than 79 years of age. Five-year RSRs for patients diagnosed from 2001 to 2008 were 0.91 (95% CI, 0.85 to 0.94) and 0.25 (95% CI, 0.10 to 0.47) for patients younger than 50 and older than 79 years, respectively. Men had inferior outcome. Upfront overall use of IM increased from 40% (2002) to 84% (2006). Only 18% of patients older than 80 years of age received IM as first-line therapy. Conclusion This large population-based study shows a major improvement in outcome of patients with CML up to 79 years of age diagnosed from 2001 to 2008, mainly caused by an increasing use of IM. The elderly still have poorer outcome, partly because of a limited use of IM.
Epithelioid haemangioendothelioma of the lung: clinical and pathological pitfalls
Authors: ME van Kasteren, AA van der Wurff, FM Palmen, A Dolman, JF Misere
Journal: European Respiratory Journal (1995)

In 1973, a 10 year old boy presented with numerous bilateral lung nodules, diagnosed as histiocytosis X by open lung biopsy. The patient was treated with prednisone until 1984. In 1993, he developed severe pain in the neck. A biopsy of the spine revealed the same tumour morphology as was seen in the lung in 1973. Immunohistological examination of the former and present biopsy led to the definitive diagnosis of epithelioid haemangioendothelioma of the lung with metastases to spine and liver. Epithelioid haemangioendothelioma of the lung is a rare soft tissue tumour of vascular origin, readily mistaken for carcinoma or, as in this case, histiocytosis. The tumour has an intermediate malignant potential. Although metastases of epithelioid haemangioendothelioma of the lung are well-known, metastatic spread to bones, as in our case, has not previously been mentioned in the literature.
Androgen-Induced Coactivator ANCCA Mediates Specific Androgen Receptor Signaling in Prostate Cancer
Authors: June X. Zou, Linlang Guo, Alexey S. Revenko, Clifford G. Tepper, Abigael T. Gemo, Hsing-Jien Kung, Hong-Wu Chen
Journal: Cancer Research (2009)

Androgen receptor (AR) plays a pivotal role in prostate cancer, primarily by regulating different gene expression programs elicited by androgen, which is important for cancer cell proliferation, survival, and differentiation. It is believed that the transcriptional function of AR is mediated largely by distinct nuclear coregulators. We report here the identification of ANCCA (also known as ATAD2), a new member of the AAA+ ATPase family proteins, as a novel AR coactivator. ANCCA interacts directly with AR and enhances its transcriptional activity, and is required for androgen-stimulated expression of a specific subgroup of genes including IGF1R, IRS-2, SGK1, and survivin. Upon androgen stimulation, ANCCA together with AR is recruited to the specific AR target genes. Suppression of ANCCA expression strongly inhibited the proliferation of androgen-responsive or androgen-independent, AR-positive prostate cancer cells and caused a significant increase of cellular apoptosis. Strikingly, the ANCCA gene itself, located at chromosome 8q24, is highly induced by androgen in androgen-dependent prostate cancer cells and xenograft tumors. Although ANCCA is hardly detected in normal human prostate tissue, high levels of ANCCA are found in hormone-independent prostate cancer cell lines, xenograft tumor, and a subset of prostate cancers with high Gleason scores. Together, these findings suggest that ANCCA plays an important role in prostate cancer by mediating specific AR functions in cancer cell survival and proliferation. The possession of ATPase and bromodomain by ANCCA makes it an attractive target for the development of therapeutics for the disease.
Clinical and genetic diagnosis of warts, hypogammaglobulinemia, infections, and myelokathexis syndrome in 10 patients
Authors: Laura Tassone, Lucia D. Notarangelo, Vanessa Bonomi, Gianfranco Savoldi, Alberto Sensi, Annarosa Soresina, C.I. Edvard Smith, Fulvio Porta, Alessandro Plebani, Luigi D. Notarangelo, Raffaele Badolato
Journal: Journal of Allergy and Clinical Immunology (2009)
P241 PatientS’ Perceptions of Their Relationship with Healthcare Professionals Regarding Their Asthma Management: A UK Survey: Abstract P241 Table 1
Authors: M Fletcher, D Hiles, E Luck
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> Asthma is one of the most common chronic conditions in the world, with 5.4 million individuals diagnosed in the UK alone. Here, we report data from a UK-based survey, conducted to assess how patients perceive the relationship with their general practitioner (GP) or nurse with regards to their asthma management. <h3>Methods</h3> This was a cross-sectional online survey administered by YouGov plc (November 2011) to a panel of over 350,000 individuals. An e-mail was sent to panellists who had previously identified themselves as having asthma, inviting them to take part in the survey. Responses were collated and analysed by YouGov and Insight Research Group. The survey was completed by 1083 individuals; 49% were aged over 55 years and 45% were male. <h3>Results</h3> Overall, 91% of respondents reported that their asthma consultations occurred in GP practises; 69% had visited a practize nurse and 60% a GP. A total of 76% of respondents described the relationship with their healthcare professional (HCP) about their asthma management as ‘good’ or ‘very good’. However, over one-third of respondents had either never been invited to (18%), or had not always attended (17%), asthma reviews. Moreover, 56% of respondents were unaware of Personal Asthma Action Plans and only 12% were currently using one, although 90% of those doing so found it ‘very’ or ‘fairly’ useful. The majority of individuals placed the responsibility for asthma control on themselves and not their HCP (Table), even among those with average or poor symptom control. Many respondents believed that lack of asthma control was inevitable, with 81% accepting that they would experience symptoms and 86% acknowledging that asthma would have an impact on their life. <h3>Conclusions</h3> Patients have low expectations of the level of asthma control that can be achieved. Despite a good relationship with their HCP, many individuals do not attend regular asthma reviews, and awareness and use of Personal Asthma Action Plans is low. There is a clear need for continued education and initiatives to increase awareness among both HCPs and patients about asthma management plans and supported self-management.
Interferon- release assays for the diagnosis of latent Mycobacterium tuberculosis infection
Authors: O. Moran Mendoza
Journal: European Respiratory Journal (2011)

To the Editors:

In their meta-analysis, Diel et al. [1] report a superior performance of interferon-γ release assays (IGRAs) for the diagnosis of latent tuberculosis infection (LTBI) compared with the tuberculin skin test (TST), the only other test available for diagnosing LTBI.

In the absence of a gold standard for LTBI, the proper assessment of the TST, IGRAs or any other future tests intended for the diagnosis of LTBI should focus on determining their capability for predicting the development of active tuberculosis (TB), i.e. the positive and negative predictive values for progression to active TB. Alternative evidence, such as the diagnostic accuracy of the test in active TB cases, is not appropriate for assessing the test’s capability …