tbuckley/cabot-search huggingface dataset:
A direct role for vitamin D-binding protein in the pathogenesis of COPD?
Authors: S. Dimeloe, C. Hawrylowicz
Journal: Thorax (2011)

<h3>Background</h3> Studies in cystic fibrosis (CF) generally focus on inflammation present in the airway lumen. Little is known about inflammation occurring in the airway wall, the site ultimately destroyed in end-stage disease. <h3>Objective</h3> To test the hypothesis that inflammatory patterns in the lumen do not reflect those in the airway wall of children with CF. <h3>Methods</h3> Bronchoalveolar lavage (BAL) fluid and endobronchial biopsies were obtained from 46 children with CF and 16 disease-free controls. BAL cell differential was assessed using May-Gruenwald-stained cytospins. Area profile counts of bronchial tissue immunopositive inflammatory cells were determined. <h3>Results</h3> BAL fluid from children with CF had a predominance of neutrophils compared with controls (median 810×10<sup>3</sup>/ml vs 1×10<sup>3</sup>/ml, p&lt;0.0001). In contrast, subepithelial bronchial tissue from children with CF was characterised by a predominance of lymphocytes (median 961 vs 717 cells/mm<sup>2</sup>, p=0.014), of which 82% were (CD3) T lymphocytes. In chest exacerbations, BAL fluid from children with CF had more inflammatory cells of all types compared with those with stable disease whereas, in biopsies, only the numbers of lymphocytes and macrophages, but not of neutrophils, were higher. A positive culture of <i>Pseudomonas aeruginosa</i> was associated with higher numbers of T lymphocytes in subepithelial bronchial tissue (median 1174 vs 714 cells/mm<sup>2</sup>, p=0.029), but no changes were seen in BAL fluid. Cell counts in BAL fluid and biopsies were positively correlated with age but were unrelated to each other. <h3>Conclusion</h3> The inflammatory response in the CF airway is compartmentalised. In contrast to the neutrophil-dominated inflammation present in the airway lumen, the bronchial mucosa is characterised by the recruitment and accumulation of lymphocytes.
Macrophage Accumulation Associated With Rat Cardiac Allograft Rejection Detected by Magnetic Resonance Imaging With Ultrasmall Superparamagnetic Iron Oxide Particles
Authors: Shinichi Kanno, Yi-Jen Lin Wu, Paul C. Lee, Stephen J. Dodd, Mangay Williams, Bartley P. Griffith, Chien Ho
Journal: Circulation (2001)

Acute cardiac allograft rejection continues to be the cause of graft loss and contributes to the morbidity and mortality after cardiac transplantation. In this study, we report a new method for detecting organ rejection in transplantation with an MR-based technique using dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) particles. These particles ( approximately 27 nm in diameter) are known to shorten relaxation times in MRI experiments.A new rat model of heterotopic heart and lung transplantation has been developed for MRI experiments. Allotransplantations (DA-->BN) were performed (n=8), with syngeneic transplantations (BN-->BN) serving as controls (n=8). MR images were obtained with a gradient echo method. At postoperative day 7, allotransplants developed moderate rejection as determined histopathologically. A significant reduction in MR signal intensity was observed after USPIO injection into rats with allotransplanted hearts. Syngeneic transplants showed no differences in MR signal intensity before and after USPIO injections. After injection of USPIO particles at postoperative day 6, a group of allotransplanted rats was treated with cyclosporin A (3 mg/kg). Animals treated with cyclosporin A for 7 days showed no reduction in MR signal intensity after USPIO reinjection at day 14, whereas animals treated for 4 days showed a significant decrease in MR signal intensity in the transplanted hearts indicative of acute graft rejection. Pathological analysis of these animals revealed that dextran-coated USPIO particles were taken up by the infiltrating macrophages that accumulated within the rejecting cardiac graft.This MRI method offers promise as a noninvasive method for detecting transplant allograft rejection.
La Polyarthrite Masculine
Authors: J. Forestier, F. Jacqueline
Journal: Annals of the Rheumatic Diseases (1952)

Les poussees ulterieures sont declenchees soit par le meme facteur, soit par d'autres. 11est A noter que des cas de polyarthrite ayant debutI avant 20 ans et stabilises les annees suivantes ont presente a nouveau une poussee quelquefois severe quand 264
3-BrPA eliminates human bladder cancer cells with highly oncogenic signatures via engagement of specific death programs and perturbation of multiple signaling and metabolic determinants
Authors: Eumorphia G. Konstantakou, Gerassimos E. Voutsinas, Athanassios D. Velentzas, Aggeliki-Stefania Basogianni, Efthimios Paronis, Evangelos Balafas, Nikolaos Kostomitsopoulos, Konstantinos N. Syrigos, Ema Anastasiadou, Dimitrios J. Stravopodis
Journal: Molecular Cancer (2015)

Urinary bladder cancer is one of the most fatal and expensive diseases of industrialized world. Despite the strenuous efforts, no seminal advances have been achieved for its clinical management. Given the importance of metabolic reprogramming in cancer cell survival and growth, we have herein employed 3-BrPA, a halogenated derivative of pyruvate and historically considered inhibitor of glycolysis, to eliminate bladder cancer cells with highly oncogenic molecular signatures.Bladder cancer cells were exposed to 3-BrPA in the absence or presence of several specific inhibitors. Cell viability was determined by MTT and flow-cytometry assays; cell death, signaling activity and metabolic integrity by Western blotting and immunofluorescence; mutant-gene profiling by DNA sequencing; and gene expression by RT-sqPCR.3-BrPA could activate dose-dependent apoptosis (type 1 PCD) and regulated necrosis (type 3 PCD) of T24 (grade III; H-Ras(G12V); p53(ΔY126)), but not RT4 (grade I), cells, with PARP, MLKL, Drp1 and Nec-7-targeted components critically orchestrating necrotic death. However, similarly to RIPK1 and CypD, p53 presented with non-essential contribution to 3-BrPA-induced cellular collapse, while reactivation of mutant p53 with PRIMA-1 resulted in strong synergism of the two agents. Given the reduced expression of MPC components (likely imposing mitochondrial dysfunction) in T24 cells, the suppression of constitutive autophagy (required by cells carrying oncogenic Ras; also, type 2 PCD) and derangement of glucose-homeostasis determinants by 3-BrPA critically contribute to drug-directed depletion of ATP cellular stores. This bioenergetic crisis is translated to severe dysregulation of Akt/FoxO/GSK-3, mTOR/S6, AMPK and MAPK (p44/42, p38 and SAPK/JNK) signaling pathways in 3-BrPA-treated T24 cells. Sensitivity to 3-BrPA (and tolerance to glucose deprivation) does not rely on B-Raf(V600E) or K-Ras(G13D) mutant oncogenic proteins, but partly depends on aberrant signaling activities of Akt, MAPK and AMPK kinases. Interestingly, MCT1- and macropinocytosis-mediated influx of 3-BrPA in T24 represents the principal mechanism that regulates cellular responsiveness to the drug. Besides its capacity to affect transcription in gene-dependent manner, 3-BrPA can also induce GLUT4-specific splicing silencing in both sensitive and resistant cells, thus dictating alternative routes of drug trafficking.Altogether, it seems that 3-BrPA represents a promising agent for bladder cancer targeted therapy.
Asthma morbidity 6 yrs after an effective asthma self-management programme in a Maori community
Authors: W.j D'souza, T Slater, C Fox, B Fox, H Te Karu, T Gemmell, M.m Ratima, N.e Pearce, R.b Beasley
Journal: European Respiratory Journal (2000)

A 6-month Maori community-based asthma self-management programme, involving a "credit card" asthma self-management plan, has previously been shown to be an effective and acceptable system for reducing asthma morbidity. The effectiveness of the asthma self-management programme and participants9 self-management behaviour was assessed 6 yrs after the formal end of the programme. Participants were surveyed at the time of enrollment, and 1, 2, and 6 yrs after completing the programme. In each survey, participants were questioned on markers of asthma morbidity and use of medical services during the previous 12 months. Self-management behaviour was assessed using a questionnaire at 2 years and 6 yrs. Of the 69 original participants, 47 (68%) were surveyed after 6 yrs. They generally had reduced severe asthma morbidity and emergency use of health services from baseline. In particular, the proportion who had an emergency visit to a general practitioner had decreased from 41% to 18% (p=0.02). However, the percentage of nights woken due to asthma had returned to preintervention levels, and the proportion of participants taking prescribed regular inhaled steroid had decreased from 91% to 53% (p&lt;0.001). Compared with 2 yrs after completion of the asthma programme, self-management behaviour had also deteriorated, with 29% versus 73% (p&lt;0.001) using their peak flow meter daily when their asthma was "getting bad" and 41% versus 86% (p&lt;0.001) using the "credit card" plan to increase the amount of inhaled steroids in the last year. Although the programme participants were still experiencing reduced morbidity from their asthma 6 yrs after the end of the self-management programme, the benefits were less than those observed at 2 yrs. These findings suggest that under-recognition and under-treatment of asthma with appropriate amounts of inhaled steroids is a major factor contributing to asthma morbidity in this indigenous rural community. To obtain enduring benefits from a self-management system of care continued reinforcement of self-management skills seems to be an essential component of any follow-up.
Effect of increased lung volume on sleep disordered breathing in patients with sleep apnoea
Authors: R C Heinzer, M L Stanchina, A Malhotra, A S Jordan, S R Patel, Y-L Lo, A Wellman, K Schory, L Dover, D P White
Journal: Thorax (2006)

Background: Previous studies have shown that changes in lung volume influence upper airway size and resistance, particularly in patients with obstructive sleep apnoea (OSA), and that continuous positive airway pressure (CPAP) requirements decrease when the lung volume is increased. We sought to determine the effect of a constant lung volume increase on sleep disordered breathing during non-REM sleep. Methods: Twelve subjects with OSA were studied during non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. The increase in lung volume due to CPAP (at a therapeutic level) was determined with four magnetometer coils placed on the chest wall and abdomen. CPAP was then stopped and the subjects were studied for 1 hour in three conditions (in random order): (1) no treatment (baseline); (2) at "CPAP lung volume", with the increased lung volume being reproduced by negative extrathoracic pressure alone (lung volume 1, LV1); and (3) 500 ml above the CPAP lung volume(lung volume 2, LV2). Results: The mean (SE) apnoea/hypopnoea index (AHI) for baseline, LV1, and LV2, respectively, was 62.3 (10.2), 37.2 (5.0), and 31.2 (6.7) events per hour (p = 0.009); the 3% oxygen desaturation index was 43.0 (10.1), 16.1 (5.4), and 12.3 (5.3) events per hour (p = 0.002); and the mean oxygen saturation was 95.4 (0.3)%, 96.0 (0.2)%, 96.3 (0.3)%, respectively (p = 0.001). Conclusion: An increase in lung volume causes a substantial decrease in sleep disordered breathing in patients with OSA during non-REM sleep.
Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of Eomesodermin
Authors: Michael A. Curran, Theresa L. Geiger, Welby Montalvo, Myoungjoo Kim, Steven L. Reiner, Aymen Al-Shamkhani, Joseph C. Sun, James P. Allison
Journal: The Journal of Experimental Medicine (2013)

4-1BB agonist antibody treatment induces a population of KLRG1+ T cells that infiltrate melanoma tumors. We investigated the origin and function of these cells, as well as their place within established T cell paradigms. We find that these T cells, particularly the CD4 lineage, represent a novel phenotype characterized by enhanced, multipotent cytotoxicity. Distinct from described polarities, this T cell phenotype is driven by the T-box transcription factor Eomesodermin. Formation of this phenotype requires 4-1BB signaling on both T and antigen-presenting cells and the resulting production of the cytokines IL-27, IL-15, and IL-10. Furthermore, we find CD4+ T cells bearing the signature features of this phenotype in the livers of mice infected with both bacterial and viral intracellular pathogens, suggesting a role for these cells in infectious immunity. These T cells constitute a novel phenotype that resolves multiple questions associated with 4-1BB activation, including how 4-1BB enhances tumor-specific cytotoxicity and how 4-1BB can promote tumor immunity while repressing autoimmunity.
Recreational soccer is an effective health-promoting activity for untrained men
Authors: P Krustrup, J J Nielsen, B R Krustrup, J F Christensen, H Pedersen, M B Randers, P Aagaard, A-M Petersen, L Nybo, J Bangsbo
Journal: British Journal of Sports Medicine (2008)

To examine the effects of regular participation in recreational soccer on health profile, 36 healthy untrained Danish men aged 20–43 years were randomised into a soccer group (SO; n = 13), a running group (RU; n = 12) and a control group (CO; n = 11). Training was performed for 1 h two or three times per week for 12 weeks; at an average heart rate of 82% (SEM 2%) and 82% (1%) of HR max for SO and RU, respectively. During the 12 week period, maximal oxygen uptake increased (p&lt;0.05) by 13% (3%) and 8% (3%) in SO and RU, respectively. In SO, systolic and diastolic blood pressure were reduced (p&lt;0.05) from 130 (2) to 122 (2) mm Hg and from 77 (2) to 72 (2) mm Hg, respectively, after 12 weeks, with similar decreases observed for RU. After the 12 weeks of training, fat mass was 3.0% (2.7 (0.6) kg) and 1.8% (1.8 (0.4) kg) lower (p&lt;0.05) for SO and RU, respectively. Only SO had an increase in lean body mass (1.7 (0.4) kg, p&lt;0.05), an increase in lower extremity bone mass (41 (8) g, p&lt;0.05), a decrease in LDL-cholesterol (2.7 (0.2) to 2.3 (0.2) mmol/l; p&lt;0.05) and an increase (p&lt;0.05) in fat oxidation during running at 9.5 km/h. The number of capillaries per muscle fibre was 23% (4%) and 16% (7%) higher (p&lt;0.05) in SO and RU, respectively, after 12 weeks. No changes in any of the measured variables were observed for CO. In conclusion, participation in regular recreational soccer training, organised as small-sided drills, has significant beneficial effects on health profile and physical capacity for untrained men, and in some aspects it is superior to frequent moderate-intensity running.
Effect of 1 year daily treatment with 400 microg budesonide (Pulmicort Turbuhaler) in newly diagnosed asthmatics
Authors: K Osterman, M Carlholm, J Ekelund, J Kiviloog, K Nikander, L Nilholm, P Salomonsson, V Strand, P Venge, O Zetterstrom
Journal: European Respiratory Journal (1997)

The aim of this study was to investigate whether treatment with a low daily dose of 400 microg inhaled budesonide (Pulmicort Turbuhaler) in newly diagnosed asthmatics could influence the course of asthma. Seventy five adult patients, mostly with mild asthma, diagnosed during the previous year and bronchial hyperresponsiveness, participated in a double-blind, randomized, parallel-group multicentre study. They were treated with budesonide 200 microg b.i.d. or placebo, delivered via Turbuhaler for 12 months and followed-up for another 6 months without inhaled steroid treatment. Airway function, symptom scores, reactivity to histamine and inflammatory indices in blood were assessed. The mean increase in morning peak expiratory flow (PEF) was 28 L x min(-1) after budesonide treatment compared with no increase in the placebo group (p=0.011). The provocative dose of histamine causing a 20% fall in forced expiratory volume in one second (PD20) (geometric mean) increased in the budesonide group by approximately two doubling dose steps, but not in the placebo group (p=0.0003). The difference between groups with regard to improvement in asthma symptom scores and inflammatory indices did not reach statistical significance. During the 6 month follow-up, the PEF values of the patients who had previously been treated with budesonide decreased by 18 L x min(-1) while the PD20 decreased by approximately one doubling dose step. In conclusion, early treatment with a low dose of budesonide improves airway function and decreases bronchial responsiveness, but the improvements are short-lasting without continued treatment.
Cellular Basis of Reduced Cortical Reelin Expression in Schizophrenia
Authors: Sharon L. Eastwood, Paul J. Harrison
Journal: American Journal of Psychiatry (2006)

The authors' goals were to establish the cellular origin of the reduced cortical reelin expression that occurs in schizophrenia and to relate it to markers of synaptic pathology.In situ hybridization was used to quantify reelin mRNA in the hippocampal formation and dorsolateral prefrontal cortex of brains from 13 subjects with schizophrenia and 12 subjects without schizophrenia. Results were correlated with the expression of three synaptic protein genes in the dentate gyrus.Reelin mRNA was expressed by layer I neurons, interneurons, and interstitial white matter neurons. In subjects with schizophrenia, less reelin mRNA was expressed by interstitial white matter neurons in the hippocampal formation and by all three cell types in the prefrontal cortex. Reelin and synaptic protein expression correlated positively.Interstitial white matter neurons, presumed remnants of the cortical subplate, contribute to the reduction in reelin mRNA in schizophrenia. Down-regulation of reelin expression may in turn contribute to the synaptic pathology of the disorder.
Is High and Growing Spending on Cancer Treatment and Prevention Harmful to the United States Economy?
Authors: Mark V. Pauly
Journal: Journal of Clinical Oncology (2007)

I have been asked to offer some thoughts on the question of whether the economic consequences of current levels and rates of growth in spending on cancer treatment and prevention pose a problem for the US economy. I will interpret “pose a problem” as doing harm to the economy and the people who live, work, and consume in that economy; even this refinement will still require some discussion of what we might mean by “harm,” and, for that matter, what we might mean by “the US economy.” I offer two propositions, one certain and the other tentative. The certain proposition is this: No one can prove that cancer spending harms the economy. The tentative proposition must be tentative because data are incomplete (and sometimes nearly nonexistent) and concepts are vague, but here it is: current levels of spending and growth in spending probably benefit the economy, but the benefit may well be modest.
Phospholipase D Meets Wnt Signaling: A New Target for Cancer Therapy
Authors: Dong Woo Kang, Kang-Yell Choi, Do Sik Min
Journal: Cancer Research (2011)

Abstract Phospholipase D (PLD) has been increasingly recognized as a critical regulator of cell proliferation and tumorigenesis. PLD regulates downstream effectors by generating phosphatidic acid (PA), and the expression and activity of PLD are elevated in many different types of human cancer. Aberrant activation of Wnt/β-catenin signaling, followed by hyper-activation of target genes, is linked to a wide range of cancers. New studies reveal a direct connection between the PLD and the Wnt signaling pathways; PLD is a transcriptional target of β-catenin/T-cell factor (TCF) and reinforces Wnt/β-catenin signaling related with cellular transformation. In this review, we discuss the emerging importance of PLD and PA in the Wnt/β-catenin signaling network, which is associated with tumorigenesis, and suggest that the PLD/PA signaling pathway is a potential therapeutic target for the treatment of cancer. Cancer Res; 71(2); 293–7. ©2011 AACR.
Long-term efficacy of infliximab treatment for AA-amyloidosis secondary to chronic inflammatory arthritis
Authors: T Keersmaekers, K Claes, D R Kuypers, K de Vlam, P Verschueren, R Westhovens
Journal: Annals of the Rheumatic Diseases (2009)

Secondary AA-amyloidosis is sometimes associated with chronic inflammatory arthritis, such as rheumatoid arthritis (RA) and spondylarthropathies (SpA), with an extracellular accumulation of amyloid proteins in the tissues of various organs. This amyloid is composed of serum amyloid P-component (SAP), serum amyloid A (SAA), an acute phase protein, and proteoglycans. Renal involvement is the most frequent manifestation of secondary amyloidosis, usually presenting with asymptomatic proteinuria.

According to earlier literature, the prognosis of AA-amyloidosis was considered very poor. Treatment with corticosteroids and immunosuppressive drugs, mainly alkylating agents, consisted of adequate suppression of the underlying inflammatory process. Recently, eprodisate was shown to slow the decline in renal function by inhibition of the production of …
Migration inhibition with various cell fractions in human colorectal cancer.
Authors: P R Armitstead, G Gowland
Journal: Gut (1975)

The unseparated leucocytes, separated mononuclear cells and granulocytes of six control subjects and nine patients with colorectal cancer have been studied by a direct cell migration inhibition technique. A migratory index was calculated from the migration in the presence and absence of a perchloric acid extract of large bowel tumours. In 10% homologous AB serum, no significant migration inhibition occurred with any of the cells from control subjects. Five of the nine cancer patients showed significant inhibition with their unseparated leucocytes, seven of seven with their mononuclear cells, and none of nine with their granulocytes. In 10% autologous serum, some controls exhibited migration inhibition with their unseparated leucocytes and their granulocyte fraction, but not with the mononuclear cell fraction. Migration inhibition was also now apparent in the granulocyte fraction of the cancer patients. It is concluded that, with a soluble tumour antigen preparation, a mononuclear cell population increases the sensitivity of the direct migration inhibition test and that autologous serum may interfere directly with the migration of granulocytes, by an action not dependent upon the release of inhibitory factors from sensitized lymphocytes. This could explain some of the inconsistencies of the assay when using an unseparated leucocyte population.
General anaesthesia versus local anaesthesia for carotid surgery (GALA): a multicentre, randomised controlled trial
Authors: S C Lewis, C P Warlow, A R Bodenham, B Colam, P M Rothwell, D Torgerson, D Dellagrammaticas, M Horrocks, C Liapis, A P Banning, M Gough, M J Gough
Journal: The Lancet (2008)