tbuckley/cabot-search huggingface dataset:
Prognostic significance of hypoxia-inducible factor-1 , TWIST1 and Snail expression in resectable non-small cell lung cancer
Authors: J-J Hung, M-H Yang, H-S Hsu, W-H Hsu, J-S Liu, K-J Wu
Journal: Thorax (2009)

<h3>Background:</h3> Metastasis is the most common cause of disease failure and mortality for non-small cell lung cancer (NSCLC) after surgical resection. Snail and TWIST1 are epithelial-mesenchymal transition (EMT) regulators which induce metastasis. Intratumoral hypoxia followed by stabilisation of hypoxia-inducible factor 1α (HIF-1α) promotes metastasis through regulation of certain EMT regulators. The aim of this study was to evaluate the prognostic value of HIF-1α, TWIST1 and Snail expression in patients with resectable NSCLC. <h3>Methods:</h3> A retrospective analysis of 87 patients with resectable NSCLC from Taipei Veterans General Hospital between 2003 and 2004 was performed using immunohistochemistry to analyse HIF-1α, TWIST1 and Snail expression. The association between HIF-1α, TWIST1 and Snail expression and patients' overall and recurrence-free survivals was investigated. <h3>Results:</h3> Overexpression of HIF-1α, TWIST1 or Snail was shown in 32.2%, 36.8% and 55.2% of primary tumours, respectively. Overexpression of HIF-1α, TWIST1 or Snail in primary NSCLCs was associated with a shorter overall survival (p = 0.005, p = 0.026, p = 0.009, respectively), and overexpression of HIF-1α was associated with a shorter recurrence-free survival (p = 0.016). We categorised the patients into four groups according to the positivity of HIF-1α/TWIST1/Snail to investigate the accumulated effects of these markers on survival. Co-expression of more than two markers was an independent prognostic indicator for both recurrence-free survival and overall survival (p = 0.004 and p&lt;0.001, respectively, by multivariate Cox proportional hazards model). <h3>Conclusions:</h3> Co-expression of more than two markers from HIF-1α, TWIST1 and Snail is a significant prognostic predictor in patients with NSCLC.
Review of current best practice and priorities for research in radiation oncology for elderly patients with cancer: the International Society of Geriatric Oncology (SIOG) task force
Authors: I.H. Kunkler, R. Audisio, Y. Belkacemi, M. Betz, E. Gore, S. Hoffe, Y. Kirova, P. Koper, J.-L. Lagrange, A. Markouizou, R. Pfeffer, S. Villa
Journal: Annals of Oncology (2014)
Shock-Induced Figure-of-Eight Reentry in the Isolated Rabbit Heart
Authors: Isabelle Banville, Richard A. Gray, Raymond E. Ideker, William M. Smith
Journal: Circulation Research (1999)

The patterns of transmembrane potential on the whole heart during and immediately after fibrillation-inducing shocks are unknown. To study arrhythmia induction, we recorded transmembrane activity from the anterior and posterior epicardial surface of the isolated rabbit heart simultaneously using 2 charge-coupled device cameras (32,512 pixels, 480 frames/second). Isolated hearts were paced from the apex at a cycle length of 250 ms. Two shock coils positioned inside the right ventricle (-) and atop the left atrium (+) delivered shocks at 3 strengths (0.75, 1.5, and 2.25 A) and 6 coupling intervals (130 to 230 ms). The patterns of depolarization and repolarization were similar, as is evident in the uniformity of action potential duration at 75% repolarization (131.4¿8.3 ms). At short coupling intervals (<180 ms), shocks hyperpolarized a large portion of the ventricles and produced a pair of counterrotating waves, one on each side of the heart. The first beat after the shock was reentrant in 90% of short coupling interval episodes. At long coupling intervals (>180 ms), increasingly stronger shocks depolarized an increasingly larger portion of the heart. The first beat after the shock was reentrant in 18% of long coupling interval episodes. Arrhythmias were most often induced at short coupling intervals (98%) than at long coupling intervals (35%). The effect and outcome of the shock were related to the refractory state of the heart at the time of the shock. Hyperpolarization occurred at short coupling intervals, whereas depolarization occurred at long coupling intervals. Consistent with the "critical point" hypothesis, increasing shock strength and coupling interval moved the location where reentry formed (away from the shock electrode and pacing electrode, respectively).
Action potentials, afterpotentials, and arrhythmias.
Authors: P F Cranefield
Journal: Circulation Research (1977)

Triggered activity must be added to spontaneous activity and to circus movement as a cause for extrasystoles and tachycardias of either atrial or ventricular origin. The activity of a triggerable focus requires phase 4 depolarization caused by an afterpotential; this distinguishes it from the activity seen in circus movement. A triggerable focus becomes rhythmically active only if driven at a critical rate or by a critically timed premature impulse; this distinguishes it from a focus of spontaneous or automatic activity. The ease of triggering a triggerable focus increases in the presence of catecholamines; triggerable foci in the atrium become quiescent when exposed to acetylcholine. At the present time, fibers within the coronary sinus provide the most persuasive example of triggered activity as a possible cause of arrhythmias of clinical significance. It is possible that the coupled extrasystoles of digitalis toxicity may be triggered; there is every reason to believe that further examples of triggered arrhythmias of possible clinical significance will be discovered.
Allergic bronchopulmonary disease caused by Curvularia lunata and Drechslera hawaiiensis.
Authors: R McAleer, D B Kroenert, J L Elder, J H Froudist
Journal: Thorax (1981)

Three patients who developed bronchoceles caused by fungi other than Aspergillus sp are described. The first patient presented for investigation of a lesion at the right hilum on chest radiograph and a raised blood eosinophil count. A bronchogram showed complete block of the apical segmental bronchus which at operation was shown to be caused by inspissated material. The second patient was investigated because of a cough productive of plugs of sputum and irregular opacities in both upper zones on chest radiograph and a raised blood eosinophil count. This only cleared after one month on high dose oral prednisone therapy. The third patient with a previous history of left lingular pneumonia and bronchiectasis of the lingular segment of the left upper lobe was investigated three years later for right basal shadowing and a raised blood eosinophil count. The radiograph cleared after one month on high dose oral prednisone treatment. The aetiological agents in these cases were dematiaceous hyphomycetes, fungi ubiquitous in nature, and also agents of plant disease. The causal fungi, Curvularia lunata and Drechslera hawaiiensis, have on a few occasions been reported as causing human disease but in cases quite dissimilar to the three reported here. Septate branching dematiaceous mycelium was consistently seen in the clinical material and isolated from successive sputum specimens from each patient. Immunodiffusion tests from the third patient gave positive results for both fungi. Intraperitoneal inoculations of C lunata and D. hawaiiensis into Swiss white mice proved the pathogenicity of these isolates.
Strength-interval relations in a chronic canine model of myocardial infarction. Implications for the interpretation of electrophysiologic studies.
Authors: E L Michelson, J F Spear, E N Moore
Journal: Circulation (1981)

Fifteen adult mongrel dogs underwent two-stage occlusion of the mid- or distal left anterior descending coronary artery and then a reperfusion stage. The dogs were studied 3-30 days later to determine strength-interval relations in a canine model of chronic myocardial infarction. These dogs were susceptible to the initiation of sustained ventricular tachyarrhythmias with the introduction of one, two or three ventricular extrastimuli. Using unipolar cathodal stimuli with a pulse width of 2 msec, strength-interval curves were constructed from measurements made at multiple sites in the distribution of occluded and nonoccluded vessels during drive pacing at a cycle length of 300 msec. At 56 normal sites, ventricular refractory periods measured at twice-diastolic-excitability threshold approximated the relative refractory periods (mean absolute difference 3 msec), but were variably longer than effective refractory periods (mean difference 18 msec, range 4-29 msec). At 51 infarct sites, differences between ventricular refractory periods measured at twice-diastolic-excitability threshold and both relative refractory periods (mean difference 13 msec, range -60 to +18 msec) and effective refractory periods (mean difference 28 msec, range 1-60 msec) were markedly disparate. These differences were further exaggerated after administration of i.v. procainamide. These findings suggest limitations in interpreting the results of programmed pacing studies performed using stimuli of twice-threshold intensity.
Tumour necrosis factor receptor associated periodic syndrome (TRAPS) with central nervous system involvement
Authors: K Minden
Journal: Annals of the Rheumatic Diseases (2004)

Tumour necrosis factor receptor associated periodic syndrome (TRAPS) is an autosomal dominant disorder resulting from mutations in the TNFRSF1A gene,1 characterised by recurrent attacks of fever, abdominal pain, severe myalgia, skin rashes, conjunctivitis, and/or periorbital oedema.2,3 These symptoms, which are partially explained by the unopposed action of tumour necrosis factor (TNF) owing to decreased soluble TNF receptor 1 (sTNFRSF1A) serum levels,4 can be alleviated by administration of etanercept, which is a TNFRSF1B (TNFR2) p75:Fc fusion protein.2,5

We describe a family in which one of three affected members with central nervous system (CNS) symptoms developed a demyelinating disorder suspected to be a feature of TRAPS.

A 20 year old white man and his 25 year old sister had complained about recurrent attacks of fever, abdominal and loin pain, severe myalgia, skin lesions, sore throat, conjunctivitis, and periorbital oedema since early childhood. These attacks had come at irregular intervals, lasted for 2–3 weeks, and were accompanied by greatly increased acute phase reactants. During childhood both patients had …
Rescue of Monocrotaline-Induced Pulmonary Arterial Hypertension Using Bone Marrow–Derived Endothelial-Like Progenitor Cells
Authors: Yidan D. Zhao, David W. Courtman, Yupu Deng, Lakshmi Kugathasan, Qiuwang Zhang, Duncan J. Stewart
Journal: Circulation Research (2005)

Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance caused by narrowing and loss of pulmonary microvasculature, which in its late stages becomes refractory to traditional therapies. We hypothesized that bone marrow–derived endothelial progenitor cells (EPCs), which normally function to repair and regenerate blood vessels, would restore pulmonary hemodynamics and increase microvascular perfusion in the rat monocrotaline (MCT) model of PAH. Mononuclear cells were isolated from the bone marrow of syngeneic Fisher-344 rats by Ficoll gradient centrifugation and cultured for 7 to 10 days in endothelial growth medium. Fluorescently labeled endothelial-like progenitor cells (ELPCs) engrafted at the level of the distal pulmonary arterioles and incorporated into the endothelial lining in the MCT-injured lung. The administration of ELPCs 3 days after MCT nearly completely prevented the increase in right ventricular systolic pressure seen at 3 weeks with MCT alone (31.5±0.95 versus 48±3 mm Hg, respectively; P &lt;0.001), whereas injection of skin fibroblasts had no protective effect (50.9±5.4 mm Hg). Delayed administration of progenitor cells 3 weeks after MCT prevented the further progression of PAH 2 weeks later (ie, 5 weeks after MCT), whereas only animals receiving ELPCs transduced with human endothelial NO-synthase (eNOS) exhibited significant reversal of established disease at day 35 (31±2 mm Hg, P &lt;0.005) compared with day 21 (50±3 mm Hg). Fluorescent microangiography revealed widespread occlusion of pulmonary precapillary arterioles 3 weeks after MCT, whereas arteriolar-capillary continuity and microvascular architecture was preserved with the administration of syngeneic ELPCs. Moreover, the delivery of ELPCs to rats with established PAH resulted in marked improvement in survival, which was greatest in the group receiving eNOS-transduced cells. We conclude that bone marrow–derived ELPCs can engraft and repair the MCT-damaged lung, restoring microvasculature structure and function. Therefore, the regeneration of lung vascular endothelium by injection of progenitor cells may represent a novel treatment paradigm for patients with PAH.
Child mortality after high-titre measles vaccines in Senegal: the complete data set
Authors: Peter Aaby, Badara Samb, Francois Simondon, Hilton Whittle, Awa Marie Coll Seck, Kim Knudsen, John Bennett, Lauri Markowitz, Phillip Rhodes, Michel Garenne, Odile Leroy, Jean Pierre Beau, Ibrahima Sene
Journal: The Lancet (1991)
(22) Erythrokeratoderma variabilis (Mendes da Costa's syndrome)
Authors: W.F.G. Tucker, C.I. Harrington
Journal: British Journal of Dermatology (1986)

Journal Article (22) Erythrokeratoderma variabilis (Mendes da Costa's syndrome) Get access W.F.G. Tucker, Drs, W.F.G. Tucker, Drs Search for other works by this author on: Oxford Academic Google Scholar C.I. Harrington C.I. Harrington Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s30, 1 July 1986, Pages 67–68, https://doi.org/10.1111/j.1365-2133.1986.tb07717.x Published: 01 July 1986
Prediction of Toxicant-Specific Gene Expression Signatures after Chemotherapeutic Treatment of Breast Cell Lines
Authors: Melissa A. Troester, Katherine A. Hoadley, Joel S. Parker, Charles M. Perou
Journal: Environmental Health Perspectives (2004)

Global gene expression profiling has demonstrated that the predominant cellular response to a range of toxicants is a general stress response. This stereotyped environmental stress response commonly includes repression of protein synthesis and cell-cycle-regulated genes and induction of DNA damage and oxidative stress-responsive genes. Our laboratory recently characterized the general stress response of breast cell lines derived from basal-like and luminal epithelium after treatment with doxorubicin (DOX) or 5-fluorouracil (5FU) and showed that each cell type has a distinct response. However, we expected that some of the expression changes induced by DOX and 5FU would be unique to each compound and might reflect the underlying mechanisms of action of these agents. Therefore, we employed supervised analyses (significance analysis of microarrays) to identify genes that showed differential expression between DOX-treated and 5FU-treated cell lines. We then used cross-validation analyses and identified genes that afforded high predictive accuracy in classifying samples into the two treatment classes. To test whether these gene lists had good predictive accuracy in an independent data set, we treated our panel of cell lines with etoposide, a compound mechanistically similar to DOX. We demonstrated that using expression patterns of 100 genes we were able to obtain 100% predictive accuracy in classifying the etoposide samples as being more similar in expression to DOX-treated than to 5FU-treated samples. These analyses also showed that toxicant-specific gene expression patterns, similar to general stress responses, vary according to cell type.
Bone Marrow Erythropoiesis in the Anemia of Infection, Inflammation, and Malignancy
Authors: Stanley Zucker, Samuel Friedman, Rita M. Lysik
Journal: Journal of Clinical Investigation (1974)

A major factor in the anemia of infection, inflammation, and malignancy is a relative failure of the bone marrow to increase erythropoiesis in response to a shortened red cell survival. The possible causes for this diminished marrow response are: (a) a reduced production of erythropoietin, or, (b) impaired bone marrow response to erythropoietin. In this report studies were performed on 6 normals, 13 patients with anemia from infection or inflammation, and 18 patients with anemia caused by advanced malignancy. Serum erythropoietin activity was measured using the posthypoxic, polycythemic mouse assay. Assessment of bone marrow response to erythropoietin was made by measuring (59)Fe-heme synthesis in bone marrow suspensions cultured for 3 days with and without the addition of erythropoietin. The results showed that marrow heme synthesis was increased in erythropoietin-treated cultures as compared with saline control cultures by 66+/-8% (mean +/-SE) in normals, 101+/-10% in patients with infection or inflammation, and 31+/-5% in malignancy. Serum erythropoietin levels were consistently diminished relative to expected levels for the degree of anemia in the infection-inflammatory group, but not in malignancy. In these patients, plasma inhibitors to the biological activity of erythropoietin were not detected in vitro. These studies suggest that another factor to consider in the anemia of malignancy is a decreased bone marrow response to erythropoietin. In the anemia of infection-inflammation, marrow response to erythropoietin is normal, but serum levels of erythropoietin are decreased relative to the degree of anemia.
P21 The relationship between employment status, work productivity and quality of life among patients with COPD: Cross-sectional analysis of the Birmingham COPD Cohort
Authors: K Kalirai, P Adab, R Jordan, D Fitzmaurice, J Ayres
Journal: Thorax (2013)

<h3>Introduction</h3> Health related quality of life (HRQoL) tends to be lower among COPD patients, as a result of associated symptoms, comorbidities and the impact of disease on daily life. However, little is known about the association between employment status and HRQoL among COPD patients. <h3>Aims</h3> We examined the relationships between HRQoL and employment status and occupational performance among patients with COPD. <h3>Methods</h3> 2000 patients with COPD from primary care are being recruited into the Birmingham COPD cohort study. In addition to clinical data, employment status, work performance and HRQoL were assessed. Work performance was measured using the SPS-6 presenteeism questionnaire. HRQoL was measured using the St George’s respiratory questionnaire (SGRQ-C). Interim baseline data was used to assess associations between HRQoL and employment status and HRQoL and occupational performance. Multivariate analyses were used to adjust for potential confounders. Model 1 adjusted for age, sex and smoking status. Model 2 additionally adjusted for disease severity (GOLD stage), number of co-morbidities and MRC dyspnoea score. <h3>Results</h3> Of the 1094 patients recruited, 14.6% (n = 160) were in work. <b>Employment status</b>: Model 1 showed that poorer quality of life was associated with lower likelihood of being in employment (OR = 0.98, 95% CI 0.96–0.99), but the effect was not seen in model 2 (OR = 1.00, 95% CI 0.99–1.02). <b>Work performance</b>: increased work performance (presenteeism) was associated with a higher quality of life in both models (B coefficient 0.13, 95% CI 0.08–0.18 and 0.12, 95% CI 0.05–0.19 in models 1 and 2 respectively). <h3>Conclusions</h3> The association between presenteeism and HRQoL has not previously been assessed in a UK COPD working population. Our findings show that after adjusting for all relevant confounders, employment status is not associated with quality of life. However, for those at work, a better quality of life is associated better work performance.
Protein Kinase C θ Affects Ca2+ Mobilization and NFAT Activation in Primary Mouse T Cells
Authors: Christa Pfeifhofer, Kurt Kofler, Thomas Gruber, Nassim Ghaffari Tabrizi, Christina Lutz, Karl Maly, Michael Leitges, Gottfried Baier
Journal: The Journal of Experimental Medicine (2003)

Protein kinase C (PKC)θ is an established component of the immunological synapse and has been implicated in the control of AP-1 and NF-κB. To study the physiological function of PKCθ, we used gene targeting to generate a PKCθ null allele in mice. Consistently, interleukin 2 production and T cell proliferative responses were strongly reduced in PKCθ-deficient T cells. Surprisingly, however, we demonstrate that after CD3/CD28 engagement, deficiency of PKCθ primarily abrogates NFAT transactivation. In contrast, NF-κB activation was only partially reduced. This NFAT transactivation defect appears to be secondary to reduced inositol 1,4,5-trisphosphate generation and intracellular Ca2+ mobilization. Our finding suggests that PKCθ plays a critical and nonredundant role in T cell receptor–induced NFAT activation.
5-ALA mediated photodynamic therapy induces autophagic cell death via AMP-activated protein kinase
Authors: Hong-Tai Ji, Li-Ting Chien, Yu-Hsin Lin, Hsiung-Fei Chien, Chin-Tin Chen
Journal: Molecular Cancer (2010)

Abstract Photodynamic therapy (PDT) has been developed as an anticancer treatment, which is based on the tumor-specific accumulation of a photosensitizer that induces cell death after irradiation of light with a specific wavelength. Depending on the subcellular localization of the photosensitizer, PDT could trigger various signal transduction cascades and induce cell death such as apoptosis, autophagy, and necrosis. In this study, we report that both AMP-activated protein kinase (AMPK) and mitogen-activated protein kinase (MAPK) signaling cascades are activated following 5-aminolevulinic acid (ALA)-mediated PDT in both PC12 and CL1-0 cells. Although the activities of caspase-9 and -3 are elevated, the caspase inhibitor zVAD-fmk did not protect cells against ALA-PDT-induced cell death. Instead, autophagic cell death was found in PC12 and CL1-0 cells treated with ALA-PDT. Most importantly, we report here for the first time that it is the activation of AMPK, but not MAPKs that plays a crucial role in mediating autophagic cell death induced by ALA-PDT. This novel observation indicates that the AMPK pathway play an important role in ALA-PDT-induced autophagy.
E6AP Mediates Regulated Proteasomal Degradation of the Nuclear Receptor Coactivator Amplified in Breast Cancer 1 in Immortalized Cells
Authors: Aparna Mani, Annabell S. Oh, Emma T. Bowden, Tyler Lahusen, Kevin L. Lorick, Allan M. Weissman, Richard Schlegel, Anton Wellstein, Anna T. Riegel
Journal: Cancer Research (2006)

Abstract The steroid receptor coactivator oncogene, amplified in breast cancer 1 (AIB1; also known as ACTR/RAC-3/TRAM-1/SRC-3/p/CIP), is amplified and overexpressed in a variety of epithelial tumors. AIB1 has been reported to have roles in both steroid-dependent and steroid-independent transcription during tumor progression. In this report, we describe that the cellular levels of AIB1 are controlled through regulated proteasomal degradation. We found that serum withdrawal or growth in high cell density caused rapid degradation of AIB1 protein, but not mRNA, in immortalized cell lines. Proteasome inhibitors prevented this process, and high molecular weight ubiquitylated species of AIB1 were detected. Nuclear export was required for proteasomal degradation of AIB1 and involved the ubiquitin ligase, E6AP. AIB1/E6AP complexes were detected in cellular extracts, and reduction of cellular E6AP levels with E6AP short interfering RNA prevented proteasomal degradation of AIB1. Conversely, overexpression of E6AP promoted AIB1 degradation. The COOH terminus of AIB1 interacted with E6AP in vitro and deletion of this region in AIB1 rendered it resistant to degradation in cells. From our results, we propose a model whereby signals promoted by changes in the cellular milieu initiate E6AP-mediated proteasomal degradation of AIB1 and thus contribute to the control of steady-state levels of this protein. (Cancer Res 2006; 66(17): 8680-6)