tbuckley/cabot-search huggingface dataset:
Development and validity testing of an IPF-specific version of the St George's Respiratory Questionnaire
Authors: J. Yorke, P. W. Jones, J. J. Swigris
Journal: Thorax (2010)

<h3>Rationale</h3> The St George9s Respiratory Questionnaire (SGRQ) is often applied to assess health-related quality of life in patients with idiopathic pulmonary fibrosis (IPF). Some SGRQ items will inevitably have weaker measurement properties than others when applied to this population. This study was conducted to develop an IPF-specific version of the SGRQ. <h3>Methods</h3> Data from a recently completed trial that enrolled subjects with IPF (n=158) who completed the SGRQ and other measures were analysed at baseline and 6 months. There were four phases to the study: (1) removing items with missing responses and using Rasch analysis on retained items to identify fit and refine item response categories; (2) development of a new scoring scheme; (3) testing agreement between original and revised versions and testing construct validity of the revised SGRQ; and (4) rewording to finalise the IPF-specific version (SGRQ-I). <h3>Results</h3> Items were removed due to missing responses (6 items) and misfit to the Rasch model (10 items); 34 items from the original 50 were retained. For certain items, disordered response thresholds were identified and corrected by collapsing response categories. A scoring algorithm was developed to place SGRQ-I scores on a scale with SGRQ scores. For any given outcome measure (eg, forced vital capacity (% predicted) and lung carbon monoxide transfer factor (% predicted), 6-min walk distance and patient-reported questionnaires), Pearson correlations were similar between pairs that included original SGRQ scores and corresponding pairs that included SGRQ-I scores. Internal reliability (Cronbach α) for each SGRQ-I component was comparable to the original SGRQ (Symptoms 0.62; Activities 0.80; Impacts 0.85). <h3>Conclusions</h3> The SGRQ-I contains items from the original SGRQ that are the most reliable for measuring health-related quality of life in patients with IPF.
Incidences of overall and site specific cancers in TNFα inhibitor treated patients with rheumatoid arthritis and other arthritides – a follow-up study from the DANBIO Registry
Authors: Lene Dreyer, Lene Mellemkjær, Anne Rødgaard Andersen, Philip Bennett, Uta Engling Poulsen, Torkell Juulsgaard Ellingsen, Torben Høiland Hansen, Dorte Vendelbo Jensen, Louise Linde, Hanne Merete Lindegaard, Anne Gitte Rasmussen Loft, Henrik Nordin, Emina Omerovic, Claus Rasmussen, Annette Schlemmer, Ulrik Tarp, Merete Lund Hetland
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To investigate the incidence of cancer in arthritis patients treated with or without TNFα inhibitors (TNF-I). <h3>Methods</h3> Arthritis patients from the DANBIO database were followed-up for cancer in the Danish Cancer Registry during 2000–2008. <h3>Results</h3> Hazard ratio for cancer overall was 1.02 (95% confidence interval (CI) 0.80-1.30) in 3347 TNF-I-treated RA patients compared to non-treated. Excess among TNF-I-treated was found for colon cancer (HR 3.52 (95%CI 1.11-11.15), whereas 6 and 0 ovarian cancer cases were observed in treated and non-treated patients, respectively. Compared to the general population, TNF-I-treated RA patients had increased risk for cancer overall, cancer in lymphatic-haematopoietic tissue and non-melanoma skin cancer, while non-RA patients had no increase in overall cancer risk. <h3>Conclusions</h3> Our results suggest that TNF-I therapy in routine care is not associated with an overall excess of cancer in arthritis patients, but observed increased risks of colon and ovarian cancer need further investigation.
Patterns of Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 Expression in Rabbit and Mouse Atherosclerotic Lesions and at Sites Predisposed to Lesion Formation
Authors: Kaeko Iiyama, Leena Hajra, Motoi Iiyama, Hongmei Li, Maria DiChiara, Benjamin D. Medoff, Myron I. Cybulsky
Journal: Circulation Research (1999)

Abstract —The recruitment of mononuclear leukocytes and formation of intimal macrophage-rich lesions at specific sites of the arterial tree are key events in atherogenesis. Inducible endothelial cell adhesion molecules may participate in this process. In aortas of normal chow-fed wild-type mice and rabbits, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), but not E-selectin, were expressed by endothelial cells in regions predisposed to atherosclerotic lesion formation. En face confocal microscopy of the mouse ascending aorta and proximal arch demonstrated that VCAM-1 expression was increased on the endothelial cell surface in lesion-prone areas. ICAM-1 expression extended into areas protected from lesion formation. Hypercholesterolemia induced atherosclerotic lesion formation in rabbits, LDL receptor and apolipoprotein E knockout mice, and Northern blot analysis demonstrated increased steady-state mRNA levels of VCAM-1 and ICAM-1, but not of E-selectin. Immunohistochemical staining revealed that VCAM-1 and ICAM-1 were expressed predominantly by endothelium in early lesions and by intimal cells in more advanced lesions. In early and advanced lesions, staining was most intense in endothelial cells at and adjacent to lesion borders. ICAM-1 staining extended into the uninvolved aorta. These expression patterns were highly reproducible in both species. The only difference was that VCAM-1 expression in endothelium over the central portions of lesions was found frequently in rabbits and rarely in mice. The expression of VCAM-1 by arterial endothelium in normal animals may represent a pathogenic mechanism or a phenotypic marker of predisposition to atherogenesis.
Influence of ASC correction on specific airway resistance using the body box
Authors: Wim Put, Chris van der Grinten
Journal: European Respiratory Journal (2013)

Pressure flow loops in the body box can be closed using ASC correction for temperature and humidity. Our normal procedure is to close loops once a months using a healthy subject and apply this ASC setting to all patients.  The aim of our study was to compare this procedure to closure of the loops for each subject in different patient groups .  Methods: measure specific airway resistance (sR, method total) with ASC setting obtained from the healthy subject and reanalyze the same measurement using automatic loop closure. The changes in ASC (%) and sR were analyzed in: healthy subjects (18), asthmatics (22), cystic fibrosis (50), obesity (20) and unselected patients (103).  Results: closing loops increased ASC significantly in unselected patients, asthma, CF and obesity (P  Conclusions: closing loops does not affect mean sRtot, but sRtot changed considerably in individual patients. The small observed differences in exhaled breath temperatures are unlikely to explain the wide open loops observed in CF patients. For sReff, sR0.5 and sRmid, sR increased closing loops. Choices made for ASC and sR considerably affect the results.
The association of fatty acid–binding protein 2 A54T polymorphism with postprandial lipemia depends on promoter variability
Authors: Ulf Helwig, Diana Rubin, Maja Klapper, Yin Li, Michael Nothnagel, Ulrich R. Fölsch, Frank Döring, Stefan Schreiber, Jürgen Schrezenmeir
Journal: Metabolism (2007)
Selective inhibition of GluN2D-containing N-methyl-D-aspartate receptors prevents tissue plasminogen activator-promoted neurotoxicity both in vitro and in vivo
Authors: Amandine Jullienne, Axel Montagne, Cyrille Orset, Flavie Lesept, David E Jane, Daniel T Monaghan, Eric Maubert, Denis Vivien, Carine Ali
Journal: Molecular Neurodegeneration (2011)

Tissue plasminogen activator (tPA) exerts multiple functions in the central nervous system, depending on the partner with which it interacts. In particular, tPA acts as a positive neuromodulator of N-methyl-D-aspartate glutamatergic receptors (NMDAR). At the molecular level, it has been proposed that the pro-neurotoxicity mediated by tPA might occur through extrasynaptic NMDAR containing the GluN2D subunit. Thus, selective antagonists targeting tPA/GluN2D-containing NMDAR signaling would be of interest to prevent noxious effects of tPA.Here, we compared three putative antagonists of GluN2D-containing NMDAR and we showed that the new compound UBP145 ((2R*,3S*)-1-(9-bromophenan-threne-3-carbonyl)piperazine-2,3-dicarboxylic acid) is far more selective for GluN2D subunits than memantine and PPDA (phenanthrene derivative (2S*, 3R*)-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid). Indeed, in vitro, in contrast to the two other compounds, UBP145 prevented NMDA toxicity only in neurons expressing GluN2D (ie, in cortical but not hippocampal neurons). Furthermore, in cultured cortical neurons, UBP145 fully prevented the pro-excitotoxic effect of tPA. In vivo, we showed that UBP145 potently prevented the noxious action of exogenous tPA on excitotoxic damages. Moreover, in a thrombotic stroke model in mice, administration of UBP145 prevented the deleterious effect of late thrombolysis by tPA.In conclusion, tPA exerts noxious effects on neurons by acting on GluN2D-containing NMDAR and pharmacological antagonists of GluN2D-containing NMDAR could be used to prevent the ability of tPA to promote neurotoxicity.
Effect of pectin on jejunal glucose absorption and unstirred layer thickness in normal man.
Authors: B Flourie, N Vidon, C H Florent, J J Bernier
Journal: Gut (1984)

The effect of high methoxy apple pectin, a carbohydrate gelling agent, on the intestinal absorption of glucose, water, and sodium was studied in man. The effect of intraluminal fibre was evaluated in 22 healthy volunteers by the intestinal perfusion technique under an occlusive balloon. The test solutions (NaCl 130 mM, KCl 5 mM, glucose or mannitol 30 mM, PEG 4000 5 g/l) were perfused just beyond the ligament of Treitz at a rate of 10 ml/min. A 25 cm segment was studied. Three concentrations of pectin were tested: 6, 10, and 15 g/l. The effect of this pectin at two concentrations, 6 and 10 g/l, on the jejunal unstirred layer thickness was evaluated in nine other healthy subjects by an electrical technique. In mannitol solution, pectin reversed water and sodium absorption, whatever its concentration was, while in glucose solution it significantly reduced absorption of water and sodium at 10 and 15 g/l only (p less than 0.01). It significantly reduced glucose absorption at all concentrations (p less than 0.01). This reduction was found to be correlated with the solution viscosity (p less than 0.01). Pectin did not alter the glucose dependent sodium transport but increased significantly (p less than 0.001) the unstirred layer thickness. These results suggested that, in healthy man, pectin acutely given may impair intestinal absorption by means of an increased unstirred layer resistance. This effect could contribute to the diminished postprandial glycaemia observed in human subjects fed pectin.
(13) Cutaneous reactions to green algae
Authors: R.B. Mallett, R.H. Champion
Journal: British Journal of Dermatology (1989)

Journal Article (13) Cutaneous reactions to green algae Get access R.B. Mallett, R.B. Mallett Addenbrooke's Hospital, Cambridge Search for other works by this author on: Oxford Academic Google Scholar R.H. Champion R.H. Champion Addenbrooke's Hospital, Cambridge Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 121, Issue s34, 1 July 1989, Page 59, https://doi.org/10.1111/j.1365-2133.1989.tb05964.x Published: 01 July 1989
Androgens Induce Prostate Cancer Cell Proliferation through Mammalian Target of Rapamycin Activation and Post-transcriptional Increases in Cyclin D Proteins
Authors: Youyuan Xu, Shao-Yong Chen, Kenneth N. Ross, Steven P. Balk
Journal: Cancer Research (2006)

Abstract Androgen receptor (AR) plays a central role in prostate cancer, with most tumors responding to androgen deprivation therapies, but the molecular basis for this androgen dependence has not been determined. Androgen [5α-dihydrotestosterone (DHT)] stimulation of LNCaP prostate cancer cells, which have constitutive phosphatidylinositol 3-kinase (PI3K)/Akt pathway activation due to PTEN loss, caused increased expression of cyclin D1, D2, and D3 proteins, retinoblastoma protein hyperphosphorylation, and cell cycle progression. However, cyclin D1 and D2 message levels were unchanged, indicating that the increases in cyclin D proteins were mediated by a post-transcriptional mechanism. This mechanism was identified as mammalian target of rapamycin (mTOR) activation. DHT treatment increased mTOR activity as assessed by phosphorylation of the downstream targets p70 S6 kinase and 4E-BP1, and mTOR inhibition with rapamycin blocked the DHT-stimulated increase in cyclin D proteins. Significantly, DHT stimulation of mTOR was not mediated through activation of the PI3K/Akt or mitogen-activated protein kinase/p90 ribosomal S6 kinase pathways and subsequent tuberous sclerosis complex 2/tuberin inactivation or by suppression of AMP-activated protein kinase. In contrast, mTOR activation by DHT was dependent on AR-stimulated mRNA synthesis. Oligonucleotide microarrays showed that DHT-stimulated rapid increases in multiple genes that regulate nutrient availability, including transporters for amino acids and other organic ions. These results indicate that a critical function of AR in PTEN-deficient prostate cancer cells is to support the pathologic activation of mTOR, possibly by increasing the expression of proteins that enhance nutrient availability and thereby prevent feedback inhibition of mTOR. (Cancer Res 2006; 66(15): 7783-92)
Reduced carbon monoxide transfer factor (TLCO) in human immunodeficiency virus type I (HIV-I) infection as a predictor for faster progression to AIDS.
Authors: R B Nieman, J Fleming, R J Coker, J R Harris, D M Mitchell
Journal: Thorax (1993)

BACKGROUND--In addition to the acute fall in carbon monoxide transfer factor (TLCO) associated with Pneumocystis carinii pneumonia (PCP) or other opportunistic lung infections, reduced TLCO occurs in HIV-I seropositive individuals without active pulmonary disease. Abnormal TLCO, in the absence of lung disease, may be a surrogate marker of HIV-I induced immunosuppression and, therefore, a predictor for a more rapid progression to AIDS. METHODS--Eighty four individuals with AIDS, who had regular pulmonary function tests before the diagnosis of AIDS was made, were identified from a cohort of patients with HIV-I infection. None had evidence of active pulmonary disease at the time of initial pulmonary function testing. The relation between the time taken to progress to AIDS and initial pulmonary function tests was examined with life table survival analysis. RESULTS--Patients with a TLCO value of &lt; 80% of predicted normal (n = 46) progressed significantly faster to AIDS, with a median time of 8.0 months compared with 16.5 months for those with a TLCO value of &gt; or = 80% (n = 38). When stratified by AIDS defining diagnosis (PCP or non-PCP), median time to PCP was also significantly related to initial TLCO values (TLCO of &lt; 80% = 9.0 months, TLCO of &gt; or = 80% = 19.0 months). Reductions in other measurements of lung function (FEV1, FVC, KCO) were not temporally associated with the development of AIDS. CONCLUSIONS--HIV-I seropositive individuals with TLCO values of &lt; 80% predicted and no evidence of lung disease progress more rapidly to AIDS than those with TLCO values of &gt; or = 80%.
STAT3 mediates cardioprotection against ischemia/reperfusion injury through metallothionein induction in the heart
Authors: Y OSHIMA, Y FUJIO, T NAKANISHI, N ITOH, Y YAMAMOTO, S NEGORO, K TANAKA, T KISHIMOTO, I KAWASE, J AZUMA
Journal: Cardiovascular Research (2004)

Objective: Activation of signal transducer and activator of transcription 3 (STAT3) was reported to be correlated with myocardial protection against ischemia/reperfusion (I/R) injury in ischemic preconditioning. Here, we tested the causality between STAT3 activity and cardioprotection. We also addressed the molecular mechanism for its cardioprotection.
The EORTC Tables Overestimate the Risk of Recurrence and Progression in Patients with Non–Muscle-Invasive Bladder Cancer Treated with Bacillus Calmette-Guérin: External Validation of the EORTC Risk Tables
Authors: Jesus Fernandez-Gomez, Rosario Madero, Eduardo Solsona, Miguel Unda, Luis Martinez-Piñeiro, Antonio Ojea, Jose Portillo, Manuel Montesinos, Marcelino Gonzalez, Carlos Pertusa, Jesus Rodriguez-Molina, Jose Emilio Camacho, Mariano Rabadan, Ander Astobieta, Santiago Isorna, Pedro Muntañola, Anabel Gimeno, Miguel Blas, Jose Antonio Martinez-Piñeiro
Journal: European Urology (2011)
Impact of chemotherapy alone, and chemotherapy plus ipilimumab, on circulating immune cells in patients with metastatic bladder cancer
Authors: Matthew D Galsky, Hahn Noah, Alexander Starodub, Ralph J Hauke, Przemyslaw Twardowski, Mark Fleming, Jingjing Qi, Guru Sonpavde, Manishkumar Patel, Jun Zhu, Uma Chippada-Venkata, Costantine Albany, Li Wang, Miriam Merad, William Oh, Nina Bhardwaj, Sacha Gnjatic, Seunghee Kim-Schulze
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Metastatic bladder cancer (MBC) is a relatively chemosensitive neoplasm yet response durations are generally short-lived. Recently, immune checkpoint blockade has demonstrated unparalleled activity in heavily pre-treated patients (pts) with MBC. The role of standard chemotherapy
Does dietary fibre stimulate intestinal epithelial cell proliferation in germ free rats?
Authors: R A Goodlad, B Ratcliffe, J P Fordham, N A Wright
Journal: Gut (1989)

The aim of the present experiment was to investigate the role of hind gut fermentation in the proliferative response of the intestinal epithelium to dietary fibre. We have previously shown that refeeding starved rats with an elemental diet supplemented with fermentable dietary fibre (but not inert bulk) is capable of stimulating intestinal epithelial cell proliferation throughout the gastrointestinal tract. Three groups of 10 germ free (GF) rats and three groups of 10 conventional (CV) rats, were used. All groups were starved for three days and then refed for two days with either an elemental diet (Flexical); Flexical plus 30% kaolin; or Flexical plus 30% of a fibre mixture. Cell production was determined by the accumulation of vincristine arrested metaphases in microdissected crypts. There was no significant difference between refeeding the rats with an elemental diet alone or with kaolin supplementation, however, the addition of fibre in CV rats was associated with a significant increase in intestinal crypt cell production rate in both the small intestine (p less than 0.01) and the colon (p less than 0.001). This marked proliferative effects of fibre was abolished in the GF rats. It can be concluded that it is the products of hind gut fermentation, not fibre per se that stimulate intestinal epithelial cell proliferation in the colon and small intestine.
Comparative study of intramuscular gold and methotrexate in a rheumatoid arthritis population from a socially deprived area
Authors: J Hamilton
Journal: Annals of the Rheumatic Diseases (2001)

To compare the risk-benefit ratio of intramuscular gold (gold sodium thiomalate (GST)) and methotrexate (MTX) in a population with rheumatoid arthritis (RA) from a deprived area.Patients with active RA were randomly assigned to open treatment with GST or MTX. Clinical and laboratory assessment was performed at 0, 12, 24, and 48 weeks. Results were analysed on an intention to treat basis.141 patients were recruited-72 were randomly allocated to GST and 69 to MTX. There were no statistically significant differences found in either the clinical or demographic variables at baseline. At 48 weeks 31 (43%) patients continued to receive GST and 43 (62%) MTX. The median MTX dose achieved was 10 mg. Gold caused significantly more withdrawals for toxicity (43% GST v 19% MTX, p=0.0026, log rank test). Both groups experienced a significant improvement in erythrocyte sedimentation rate, C reactive protein, Ritchie Articular Index, and pain score by 24 weeks (p<0.001, Friedman test). Although a trend towards an improved Health Assessment Questionnaire (HAQ) score and global wellbeing was seen in both groups, this did not reach statistical significance. No differences in efficacy were found when the two groups were compared (Mann-Whitney).GST and low dose MTX showed equivalent efficacy, but toxicity was more common in patients treated with GST. GST, although more toxic, remains a useful alternative for patients in whom MTX is contraindicated.
Alternatives to steroids?! Beneficial effects of immunosuppressant drugs in autoimmune pancreatitis: Table 1
Authors: Gitta Seleznik, Rolf Graf
Journal: Gut (2013)

<h3>Background</h3> Persistence of myofibroblasts is believed to contribute to the development of fibrosis in idiopathic pulmonary fibrosis (IPF). Transforming growth factor β1 (TGFβ1) irreversibly converts fibroblasts into pathological myofibroblasts, which express smooth muscle α-actin (α-SMA) and produce extracellular matrix proteins, such as procollagen I (α1). Reactive oxygen species produced by NADPH oxidases (NOXs) have been shown to regulate cell differentiation. It was hypothesised that NOX could be expressed in parenchymal pulmonary fibroblasts and could mediate TGFβ1-stimulated conversion of fibroblasts into myofibroblasts. <h3>Methods</h3> Fibroblasts were cultured from the lung of nine controls and eight patients with IPF. NOX4, α-SMA and procollagen I (α1) mRNA and protein expression, reactive oxygen species production and Smad2/3 phosphorylation were quantified, in the absence and in the presence of incubation with TGFβ1. Migration of platelet-derived growth factor (PDGF)-induced fibroblasts was also assessed. <h3>Results</h3> It was found that (1) NOX4 mRNA and protein expression was upregulated in pulmonary fibroblasts from patients with IPF and correlated with mRNA expression of α-SMA and procollagen I (α1) mRNA; (2) TGFβ1 upregulated NOX4, α-SMA and procollagen I (α1) expression in control and IPF fibroblasts; (3) the change in α-SMA and procollagen I (α1) expression in response to TGFβ1 was inhibited by antioxidants and by a NOX4 small interfering RNA (siRNA); (4) NOX4 modulated α-SMA and procollagen I (α1) expression by controlling activation of Smad2/3; and (5) NOX4 modulated PDGF-induced fibroblast migration. <h3>Conclusion</h3> NOX4 is critical for modulation of the pulmonary myofibroblast phenotype in IPF, probably by modulating the response to TGFβ1 and PDGF.