tbuckley/cabot-search huggingface dataset:
Poor Concordance among Nine Immunohistochemistry Classifiers of Cell-of-Origin for Diffuse Large B-Cell Lymphoma: Implications for Therapeutic Strategies
Authors: Rita Coutinho, Andrew James Clear, Andrew Owen, Andrew Wilson, Janet Matthews, Abigail Lee, Rute Alvarez, Maria Gomes da Silva, José Cabeçadas, Maria Calaminici, John G. Gribben
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The opportunity to improve therapeutic choices on the basis of molecular features of the tumor cells is on the horizon in diffuse large B-cell lymphoma (DLBCL). Agents such as bortezomib exhibit selective activity against the poor outcome activated B-cell type (ABC) DLBCL. In order for targeted therapies to succeed in this disease, robust strategies that segregate patients into molecular groups with high reliability are needed. Although molecular studies are considered gold standard, several immunohistochemistry (IHC) algorithms have been published that claim to be able to stratify patients according to their cell-of-origin and to be relevant for patient outcome. However, results are poorly reproducible by independent groups. Experimental Design: We investigated nine IHC algorithms for molecular classification in a dataset of DLBCL diagnostic biopsies, incorporating immunostaining for CD10, BCL6, BCL2, MUM1, FOXP1, GCET1, and LMO2. IHC profiles were assessed and agreed among three expert observers. A consensus matrix based on all scoring combinations and the number of subjects for each combination allowed us to assess reliability. The survival impact of individual markers and classifiers was evaluated using Kaplan–Meier curves and the log-rank test. Results: The concordance in patient's classification across the different algorithms was low. Only 4% of the tumors have been classified as germinal center B-cell type (GCB) and 21% as ABC/non-GCB by all methods. None of the algorithms provided prognostic information in the R-CHOP (rituximab plus cyclophosphamide–adriamycin–vincristine–prednisone)–treated cohort. Conclusion: Further work is required to standardize IHC algorithms for DLBCL cell-of-origin classification for these to be considered reliable alternatives to molecular-based methods to be used for clinical decisions. Clin Cancer Res; 19(24); 6686–95. ©2013 AACR.
TSLP Induces Corticosteroid Resistance In Natural Helper Cells Via STAT5 Pathway
Authors: Hiroki Kabata, Kazuyo Moro, Koichi Fukunaga, Yusuke Suzuki, Katsunori Masaki, Tomoko Betsuyaku, Shigeo Koyasu, Koichiro Asano
Journal: Journal of Allergy and Clinical Immunology (2014)
Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis
Authors: Yasuhiko Kimura, Patrick S. C. Leung, Thomas P. Kenny, Judy Van De Water, Mikio Nishioka, Andrew S. Giraud, James Neuberger, Gordon Benson, Rashmi Kaul, Aftab A. Ansari, Ross L. Coppel, M. Eric Gershwin
Journal: Hepatology (2002)

Intestinal trefoil factor (ITF) promotes epithelial cell migration and mucosal restitution during inflammation. We used real-time quantitative PCR, in situ nucleic acid hybridization, and immunohistochemistry to study the expression of the ITF gene and protein expression in the liver of primary biliary cirrhosis (PBC) and controls. There were significantly higher levels of ITF messenger RNA (mRNA) in PBC liver compared with primary sclerosing cholangitis (PSC) (P < .05) or normal controls (P < .001) and also higher in hepatitis C virus (HCV) liver (P < .05) and cryptogenic cirrhosis (P < .01) compared with normal controls. However, only in PBC was there a significant difference between small (interlobular and bile ductules) and large (intrahepatic and septal) bile ducts. Using in situ hybridization, the highest levels of ITF gene expression were localized to the large bile ducts in PBC. This differential expression of ITF was also noted at the protein level. Thus, in PBC, although 92% of large bile ducts expressed the ITF protein, only 2% of small bile ducts (P < .0001) expressed ITF. In contrast, in control livers, 34% of large bile ducts and 13% of small bile ducts expressed ITF. ITF protein is absent in small bile ducts in all stages of PBC. In conclusion, the expression of ITF may play an important role in bile duct damage. In small bile ducts, ITF production in response to damage is absent, making such cells vulnerable to damage and providing a thesis for the selective loss of small, but not large, bile ducts in PBC.
Bronchial nitric oxide is related to symptom relief during fluticasone treatment in COPD
Authors: L. Lehtimäki, H. Kankaanranta, S. Saarelainen, I. Annila, T. Aine, R. Nieminen, E. Moilanen
Journal: European Respiratory Journal (2009)

High levels of exhaled nitric oxide (NO) predict favourable response to inhaled corticosteroids in asthma, but the ability of exhaled NO or inflammatory markers in exhaled breath condensate (EBC) to predict steroid responsiveness in chronic obstructive pulmonary disease (COPD) is not known. We measured alveolar and bronchial NO output, levels of leukotriene B 4 (LTB 4 ), cysteinyl leukotrienes (cysLTs) and 8-isoprostane in EBC, spirometry, body plethysmography and symptoms in 40 subjects with COPD before and after 4 weeks of treatment with inhaled fluticasone (500 μg b.i.d. ). Five subjects (12.5%) with COPD had significant improvement in lung function during fluticasone treatment, whereas 20 subjects (50%) had significant decrease in symptoms. High baseline bronchial NO flux was associated with higher increase in forced expiratory volume in 1 s to forced vital capacity ratio (r = 0.334, p = 0.038) and more symptom relief (r = -0.317, p = 0.049) during the treatment. Baseline EBC levels of LTB 4 , cysLTs or 8-isoprostane were not related to response to fluticasone treatment. Inhaled fluticasone decreased bronchial NO flux but not alveolar NO concentration or markers in EBC. High levels of bronchial NO flux are related to symptom relief and improvement of airway obstruction during treatment with inhaled fluticasone in COPD. Markers of inflammation or oxidative stress in EBC are not related to steroid responsiveness in COPD.
The labyrinth of asthma phenotypes and exhaled NO
Authors: E BARALDI
Journal: Thorax (2001)

In this issue of Thorax Payne et al 1 suggest that it is possible to distinguish different patterns of difficult childhood asthma by measuring exhaled NO (eNO). The knowledge that severe asthma may have different phenotypes with different types of airway inflammation is not new and has been clearly shown by bronchoalveolar lavage (BAL) and airway biopsy studies in adult patients.2The potential importance of these data lies in the classification of different patterns by using a non-invasive instantaneous measurement such as eNO.

Exhaled NO levels are known to be increased in atopic asthma, to increase during an exacerbation, to decrease with anti-inflammatory therapy,3 and to rise as the dose of inhaled steroids is reduced.4 In addition, eNO levels are correlated with eosinophils in induced sputum,5 bronchial hyperresponsiveness to AMP,6 and exercise,7and to increase in the late phase following allergen challenge.8 As a diagnostic tool, eNO levels discriminated asthmatics from non-asthmatics with a high sensitivity and specificity in a group of subjects with chronic cough.9 All the above evidence supports the contention that eNO may be considered a surrogate marker of airway inflammation in asthma.10 11 

NO is a freely diffusible gas generated from l-arginine by NO synthases. These enzymes are found in many cells of the lung, including nerves, epithelial cells, alveolar macrophages, and other inflammatory cells. It has been suggested that the increased eNO levels found in asthmatic subjects result from an increase in the expression of inducible nitric oxide synthase 2 (NOS-2) in the respiratory tract induced by the action of proinflammatory cytokines.12Corticosteroids inhibit induction of NOS-212 13; however, eNO concentrations remain somewhat increased in asymptomatic patients with normal spirometric parameters, consistent with the presence of ongoing airway inflammation. Even though NOS-2 …
The benefits of chemotherapy in patient subgroups with unresectable non-small-cell lung cancer
Authors: L.J. Billingham, M.H. Cullen
Journal: Annals of Oncology (2001)

Cisplatin-based chemotherapy improves survival in advanced non-small-cell lung cancer. Using data from phase III trials of mitomycin, ifosfamide and cisplatin, this paper investigates whether the beneficial effect of chemotherapy on survival and quality of life seen overall is limited to certain patient subgroups.The survival benefit of chemotherapy was compared with standard treatment using hazard ratios for subgroups specified by stage, sex, age, histology and performance status (PS). The effect on quality of life was investigated for three subgroups defined by performance status.The overall unstratified hazard ratio for all 797 eligible patients shows a 16% reduction in the risk of death with chemotherapy (P = 0.02). This benefit was seen for both locally advanced and extensive stage disease (significantly in extensive disease). Subgroups defined by sex, age and histology consistently benefitted from chemotherapy. The hazard ratios for the three levels of performance status suggest that PS2 patients gain no survival benefit from chemotherapy. In contrast, these patients experienced the greatest improvement in quality of life during the first six weeks of chemotherapy.Subgroup analysis suggests that the prolongation of life from cisplatin-based chemotherapy is confined to PS0/1 patients. Palliation is greater in PS2 patients.
NF-ÎºBâ€“mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia
Authors: Wei A. He, Emanuele Berardi, Veronica M. Cardillo, Swarnali Acharyya, Paola Aulino, Jennifer Thomas-Ahner, Jingxin Wang, Mark Bloomston, Peter Muscarella, Peter Nau, Nilay Shah, Matthew E.R. Butchbach, Katherine Ladner, Sergio Adamo, Michael A. Rudnicki, Charles Keller, Dario Coletti, Federica Montanaro, Denis C. Guttridge
Journal: Journal of Clinical Investigation (2013)

Cachexia is a debilitating condition characterized by extreme skeletal muscle wasting that contributes significantly to morbidity and mortality. Efforts to elucidate the underlying mechanisms of muscle loss have predominantly focused on events intrinsic to the myofiber. In contrast, less regard has been given to potential contributory factors outside the fiber within the muscle microenvironment. In tumor-bearing mice and patients with pancreatic cancer, we found that cachexia was associated with a type of muscle damage resulting in activation of both satellite and nonsatellite muscle progenitor cells. These muscle progenitors committed to a myogenic program, but were inhibited from completing differentiation by an event linked with persistent expression of the self-renewing factor Pax7. Overexpression of Pax7 was sufficient to induce atrophy in normal muscle, while under tumor conditions, the reduction of Pax7 or exogenous addition of its downstream target, MyoD, reversed wasting by restoring cell differentiation and fusion with injured fibers. Furthermore, Pax7 was induced by serum factors from cachectic mice and patients, in an NF-κB-dependent manner, both in vitro and in vivo. Together, these results suggest that Pax7 responds to NF-κB by impairing the regenerative capacity of myogenic cells in the muscle microenvironment to drive muscle wasting in cancer.
Agreement between Quantiferon-TB-Gold In Tube, T-SPOT.TB and tuberculin skin testing for diagnosing latent tuberculosis infection in a contact tracing study
Authors: Neus Altet, Irene Latorre, Malú De Souza, M. Angeles Jimenez, Celia Mila, J. Solsona, E. Lara, Maria Dolors Ferrer, Joan Caylà, Jose Antonio Dominguez Benitez
Journal: European Respiratory Journal (2012)

Aim: To determine the agreement between Quantiferon-TB Gold In Tube (QFN), T-SPOT.TB and TST in diagnosing LTBI in a contact study.  Methods: 753 individuals from contact tracing studies were included in the study. In all cases QFN and TST were performed, and in 141 patients the T-SPOT was also performed. TST was negative when the induration was less than 5 mm.  Results: The QFN and TST obtained concordant result in 478 cases from the 753 patients (the overall agreement was 63%), being both tests negative in 145 cases, and positive in 333 cases. From the 275 discordant results, in only one case the TST was negative and the QFN positive (corresponds with a high degree of exposure to the index case), and in 274 cases the TST was positive and the QFN negative, corresponding in 239 cases to BCG-vaccinated patients, and without significant difference between time of exposure to the index case  With regards to the 141 patients tested with T-SPOT both in vitro tests were concordant in 120 cases (85.1%), being in 61 cases both tests negative, and in 59 cases positive. From the 21 discordant results, in 5 cases the QFN was positive and the T-SPOT negative, and in 16 cases the QFN was negative but the T-SPOT was positive, being in 15 of them the time of exposure significantly higher.  Conclusion: QFN and T-SPOT.TB have a high concordance in the diagnosis of LTBI. T-SPOT.TB shows a higher number of positive results than QFN. The main discordant results between TST and QFN should be attributed to the BCG-vaccination. Both tests seem useful for the diagnosis of LTBI in the contact studies.  The study was supported by a grant from FIS (08/1738).
Bcl-XL down-regulation suppresses the tumorigenic potential of NPM/ALK in vitro and in vivo
Authors: Addolorata Maria Luce Coluccia, Silvia Perego, Loredana Cleris, Rosalind Helen Gunby, Lorena Passoni, Edoardo Marchesi, Franca Formelli, Carlo Gambacorti-Passerini
Journal: Blood (2003)
Fifteen years experience with finger arterial pressure monitoring: assessment of the technology
Authors: B Imholz
Journal: Cardiovascular Research (1998)

We review the Finapres technology, embodied in several TNO-prototypes and in the Ohmeda 2300 and 2300e Finapres NIBP. Finapres is an acronym for FINger Arterial PRESsure, the device delivers a continuous finger arterial pressure waveform. Many papers report on the accuracy of the device in comparison with intra-arterial or with noninvasive but intermittent blood pressure measurements. We compiled the results of 43 such papers and found systolic, diastolic and mean accuracies, in this order, ranging from −48 to 30 mmHg, from −20 to 18 mmHg, and from −13 to 25 mmHg. Weighted for the number of subjects included pooled accuracies were −0.8 (SD 11.9), −1.6 (8.3) and −1.6 (7.6) mmHg respectively. Subdividing the pooled group according to criteria such as reference blood pressure, place of application, and prototype or commercial device we found no significant differences in mean differences or SD. Measurement at the finger allows uninterrupted recordings of long duration. The transmission of the pressure pulse along the arm arteries, however, causes distortion of the pulse waveform and depression of the mean blood pressure level. These effects can be reduced by appropriate filtering, and upper arm ‘return-to-flow’ calibration to bring accuracy and precision within AAMI limits. For the assessment of beat-to-beat changes in blood pressure and assessment of blood pressure variability Finapres proved a reliable alternative for invasive measurements when mean and diastolic pressures are concerned. Differences in systolic pressure are larger and reach statistical significance but are not of clinical relevance. Finger arteries are affected by contraction and dilatation in relation to psychological and physical (heat, cold, blood loss, orthostasis) stress. Effects of these phenomena are reduced by the built-in Physiocal algorithm. However, full smooth muscle contraction should be avoided in the awake patient by comforting the patient, and covering the hand. Arterial state can be monitored by observing the behaviour of the Physiocal algorithm. We conclude that Finapres accuracy and precision usually suffice for reliable tracking of changes in blood pressure. Diagnostic accuracy may be achieved with future application of corrective measures.
Competing against doping
Authors: Rajesh Kumar
Journal: British Journal of Sports Medicine (2010)

Sport is thought of as an activity that is governed by a set of rules and that which is engaged in competitively, while doping is the idea of using banned natural or synthetic substance for the purpose of enhancing sports performance. Sports goes beyond a measure of athletic excellence and the winning of trophies, medals and cash awards has become a pride to the nation and sports persons. Sports teach us about honest endeavour, commitment and fair play. The use of performance enhancement drugs is very harmful to the body. Doping in sports is not a new phenomenon; athletes have taken performance-enhancing agents since the beginning of time. The ancient Olympics in Greece were riddled with doping. In ancient Rome, gladiators drank herbal infusions to strengthen them before chariot races. The first doping death occurred in 1886 in cycling. In the early 1900, the popular doping agent was a cocktail of alcohol and strychnine. The use of performance-enhancing drugs is a form of cheating, that is quite widespread and common in sports. Performance-enhancing drugs such as stimulants, anabolic steroids, diuretics, β-blockers, etc are harmful to the health. Despite harmful effects, the sports persons are using drugs to become famous and rich. Performance enhancement may be attained fairly through good dietary nutrition and effective training and recovery programmes. Athletes require good dietary advice from early on in their career to achieve high-level sports performance. Sports must be doping-free and performance must be achieved through scientific sports coaching. Sports and games must be played in a fair manner.
Breast Cancer Prognosis Determined by Gene Expression Profiling: A Quantitative Reverse Transcriptase Polymerase Chain Reaction Study
Authors: E. Espinosa, J.A. Fresno Vara, A. Redondo, J.J. Sánchez, D. Hardisson, P. Zamora, F. Gómez Pastrana, P. Cejas, B. Martínez, A. Suárez, F. Calero, M. González Barón
Journal: Journal of Clinical Oncology (2005)

We sought to reproduce with quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) the results obtained with a 70-gene expression profile that has been described previously in breast cancer.Frozen breast cancer samples from patients who were operated on were used to isolate tumor RNA. Ninety-six patients with stage I to II disease were included. Median age was 57 years (range, 27 to 80 years). Forty-eight patients had lymph node-negative and 48 lymph node-positive disease. qRT-PCR amplifications were performed and the results were correlated with clinical data.After a minimum follow-up of 5 years, 25 patients had a relapse. The gene profile divided patients into two groups with poor and good prognosis. Significant differences with regard to grade of differentiation, size and hormone receptors were seen between the two groups. The gene profile was significantly associated with relapse-free survival and overall survival in the whole group of 96 patients. Multivariate analysis showed that only lymph node status and gene profile were significantly correlated to overall survival.qRT-PCR reproduced the results obtained with microarrays for a prognostic gene profile in women with early-stage breast cancer.
Intravesical Gemcitabine Therapy for Superficial Transitional Cell Carcinoma of the Bladder: A Phase I and Pharmacokinetic Study
Authors: Menachem Laufer, Sakkaraiappan Ramalingam, Mark P. Schoenberg, Mary Ellen Haisfield-Wolf, Eleanor G. Zuhowski, Irene N. Trueheart, Mario A. Eisenberger, Ofer Nativ, Merrill J. Egorin
Journal: Journal of Clinical Oncology (2003)

Purpose: To determine maximum-tolerated dose, toxicities, and pharmacokinetics associated with weekly intravesical gemcitabine therapy in patients with superficial bladder cancer. Patients and Methods: Fifteen patients with recurrent superficial transitional cell bladder carcinoma who experienced prior intravesical therapy failure were studied. Two to 4 weeks after complete transurethral resection, gemcitabine was administered intravesically, once weekly for 6 consecutive weeks. Dwell time was 2 hours. Pharmacokinetics of gemcitabine and its metabolite, 2′2′-difluorodeoxyuridine (dFdU), were studied in plasma and urine. Cystoscopy was repeated 6 weeks after therapy. Results: Three-patient cohorts were enrolled sequentially at doses of 500, 1,000, and 1,500 mg in 100 mL 0.9% NaCl. Two patients received 2,000 mg in 100 mL. An additional four patients received 2,000 mg in 50 mL. No grade 4 toxicity or clinically relevant myelosuppression was noted. Nine of 13 evaluable patients were recurrence-free at 12 weeks. Low concentrations of gemcitabine (≤ 1 μg/mL) were present transiently in plasma of all patients receiving 2,000 mg in 50 mL. Gemcitabine was undetectable in plasma of other patients. dFdU was undetectable in plasma of patients receiving less than 1,500 mg. At doses ≥ 1,500 mg, dFdU concentrations increased until 90 to 120 minutes and then declined little, if any. Plasma dFdU concentrations implied absorption of 0.5% to 5.5% of instilled dose. Between 61% and 100% of the gemcitabine dose was accounted for in voided urine. No dFdU was measured in voided urine. Conclusion: Intravesical gemcitabine, at doses up to 2 g/wk, is well tolerated, is associated with minimal systemic absorption, and has promising efficacy in treatment of superficial bladder cancer.
Effect of whole body hypothermia on inflammation and surfactant function in asphyxiated neonates
Authors: Daniele De Luca, Sonia Vázquez-Sánchez, Angelo Minucci, Mercedes Echaide, Marco Piastra, Giorgio Conti, Ettore D. Capoluongo, Jesus Pérez-Gil
Journal: European Respiratory Journal (2014)

T o the Editor: 

Hypothermia has become an evidence-based treatment for neonates with hypoxic-ischaemic encephalopathy (HIE) [1]. The usefulness of hypothermia is due to several mechanisms and among these the reduction in inflammation seems to play a relevant role [2, 3]. When applied as whole body hypothermia (WBH), cooling may affect other organs as well. Recent data showed better respiratory outcomes and trends towards lower inflammation in WBH-treated preterm lambs [4], suggesting its possible usefulness to reduce lung injury through the modulation of the inflammatory pathway. By contrast, experiments with hibernating animals have shown that temperature induces significant adaptive changes to the surfactant composition and structure [5]. Nevertheless, no data are currently available in humans. Two case reports have recently described an infant [6] and an adult [7] with severe lung injury, whose ventilation had been facilitated by concurrent hypothermia. Since hypothermia is an accepted therapy only for HIE, we designed a preliminary translational study to investigate the effect of WBH on inflammation and surfactant status in neonates with HIE unaffected by any pulmonary injury.

Eligible babies were neonates with HIE who required WBH according to TOBY (total body hypothermia trial) criteria [8]. Control babies were normothermic neonates matched for gestational age and SNAPPE-II (Score for Neonatal Acute Physiology and Perinatal Extension-II) score, born within 2 months of the HIE cases and needing intubation for surgical procedures during the first day of life. Both cases and controls had to be free from any pulmonary disease and fulfil the following criteria: 1) normal chest radiograph and auscultation; 2) inspiratory oxygen fraction of 0.21 to achieve arterial oxygen saturation ≥95%; 3) normal amniotic fluid; 4) no signs of infection; and 5) no congenital lung disease or complex …