tbuckley/cabot-search huggingface dataset:
Association of the Circulating Levels of the Urokinase System of Plasminogen Activation With the Presence of Prostate Cancer and Invasion, Progression, and Metastasis
Authors: Shahrokh F. Shariat, Claus G. Roehrborn, John D. McConnell, Sangtae Park, Nina Alam, Thomas M. Wheeler, Kevin M. Slawin
Journal: Journal of Clinical Oncology (2007)

To assess whether preoperative plasma levels of urokinase-type plasminogen activator (uPA) and its soluble receptor (uPAR) would predict cancer of the prostate (CaP) presence, stage, and prognosis.Plasma levels of uPA and uPAR were measured in patients who underwent radical prostatectomy for clinically localized CaP (preoperative, n = 429; postoperative, n = 76), 44 healthy men, 19 patients with metastases to regional lymph nodes, and 10 patients with bone metastases.uPA and uPAR levels were significantly elevated in patients with CaP compared with healthy men and significantly declined after prostate removal. In CaP patients, uPA and uPAR levels both increased significantly from patients with nonmetastatic CaP to patients with lymph node metastases to patients with skeletal metastases. On univariate analysis, preoperative uPA and uPAR levels were significantly elevated in patients with extracapsular extension, seminal vesicle involvement, higher prostatectomy Gleason sum, lymph node invasion, lymphovascular invasion, perineural invasion, and higher tumor volume. Higher preoperative uPAR was associated with biochemical progression in univariate analysis. Conversely, higher preoperative uPA was independently associated with biochemical progression in preoperative or postoperative multivariate models. In patients with biochemical progression, preoperative uPA and uPAR were both significantly associated with shorter postprogression total serum prostate-specific antigen doubling times, failure to respond to salvage local radiation therapy, and/or development of distant metastasis.Elevation of plasma uPA and uPAR levels in CaP patients seems to be partly caused by local release from the prostate. Plasma levels of uPA and uPAR are associated with features of biologically aggressive CaP, disease progression after radical prostatectomy, and metastasis.
Daily variations in air pollution and respiratory health in a multicentre study: the PEACE project. Pollution Effects on Asthmatic Children in Europe
Authors: W Roemer, G Hoek, B Brunekreef, J Haluszka, A Kalandidi, J Pekkanen
Journal: European Respiratory Journal (1998)

The Pollution Effects on Asthmatic Children in Europe (PEACE) study is a multicentre study of the acute effects of particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10), black smoke (BS), sulphur dioxide (SO2) and nitrogen dioxide (NO2) on the respiratory health of children with chronic respiratory symptoms. The study was conducted in the winter of 1993/1994 by 14 research centres in Europe. A total of 2,010 children, divided over 28 panels in urban and suburban locations, was followed for at least 2 months. Exposure to air pollution was monitored on a daily basis. Health status was monitored by daily peak expiratory flow (PEF) measurements and a symptom diary. The association between respiratory health and air pollution levels was calculated with time series analysis. Combined effect estimates of air pollution on PEF or the daily prevalence of respiratory symptoms and bronchodilator use were calculated from the panel-specific effect estimates. Fixed effect models were used and, in cases of heterogeneity, random effect models. No clear associations between PM10, BS, SO2 or NO2 and morning PEF, evening PEF, prevalence of respiratory symptoms or bronchodilator use could be detected. Only previous day PM10 was negatively associated with evening PEF, but only in locations where BS was high compared to PM10 concentrations. There were no consistent differences in effect estimates between subgroups based on urban versus suburban, geographical location or mean levels of PM10, BS, SO2 and NO2. The lack of association could not be attributed to a lack of statistical power, low levels of exposure or incorrect trend specifications. In conclusion, the PEACE project did not show effects of particles with a 50% cut-off aerodynamic diameter of 10 microm, black smoke, sulphur dioxide or nitrogen dioxide on morning or evening peak expiratory flow or the daily prevalence of respiratory symptoms and bronchodilator use.
Molecular phylogenetics of Stenodermatini bat genera: congruence of data from nuclear and mitochondrial DNA.
Authors: R A Van den Bussche, R J Baker, H A Wichman, M J Hamilton
Journal: Molecular Biology and Evolution (1993)

Within the tribe Stenodermatini the systematics of the complex of species allied with the genus Artibeus has generated several alternative phylogenetic hypotheses. The most recent treatment recognized four genera (Artibeus, Dermanura, Enchisthenes, and Koopmania) and suggested that the most recent common ancestor of these four genera would include the common ancestor of all other currently recognized Stenodermatini genera except Sturnira. To test this hypothesis, we examined an EcoRI-defined nuclear satellite DNA repeat and 402 bp of DNA sequence variation from the mitochondrial cytochrome b gene. Phylogenetic conclusions based on Southern blot analyses, in situ hybridization, and mitochondrial DNA sequence data indicate that Enchisthenes is not closely related to Dermanura, Artibeus, or Koopmania and that Dermanura, Artibeus, and Koopmania shared a common ancestor after diverging from the remainder of the Stenodermatini. If our conclusions are correct, then justification for recognizing Dermanura and Koopmania as generically distinct from Artibeus must be based on the magnitude of difference that distinguishes each rather than on the conclusion that to place them as congeneric with Artibeus creates a paraphyletic taxon.
Aneurysms of the coronary arteries in Kawasaki disease. An angiographic study of 30 cases.
Authors: Z Onouchi, S Shimazu, N Kiyosawa, T Takamatsu, K Hamaoka
Journal: Circulation (1982)

Thirty patients with coronary aneurysms associated with Kawasaki disease underwent coronary arteriography. Of 53 aneurysms, five were saccular, 24 sacculofusiform, 19 fusiform and five tubular. When tubular aneurysms were included in the fusiform type, the incidence of each configuration in the right coronary artery was almost the same as that in the left coronary artery. The left anterior descending coronary artery had the most aneurysms, followed by the right coronary, left main and circumflex arteries. Right coronary aneurysms always involved the bifurcation or the region from which a branch vessel arose; 13 of 31 left coronary aneurysms did not involve the bifurcation.
Hematopoietic MicroRNA-126 Protects against Renal Ischemia/Reperfusion Injury by Promoting Vascular Integrity
Authors: Roel Bijkerk, Coen van Solingen, Hetty C. de Boer, Pieter van der Pol, Meriem Khairoun, Ruben G. de Bruin, Annemarie M. van Oeveren-Rietdijk, Ellen Lievers, Nicole Schlagwein, Danielle J. van Gijlswijk, Marko K. Roeten, Zeinab Neshati, Antoine A.F. de Vries, Mark Rodijk, Karin Pike-Overzet, Yascha W. van den Berg, Eric P. van der Veer, Henri H. Versteeg, Marlies E.J. Reinders, Frank J.T. Staal, Cees van Kooten, Ton J. Rabelink, Anton Jan van Zonneveld
Journal: Journal of the American Society of Nephrology (2014)

Ischemia/reperfusion injury (IRI) is a central phenomenon in kidney transplantation and AKI. Integrity of the renal peritubular capillary network is an important limiting factor in the recovery from IRI. MicroRNA-126 (miR-126) facilitates vascular regeneration by functioning as an angiomiR and by modulating mobilization of hematopoietic stem/progenitor cells. We hypothesized that overexpression of miR-126 in the hematopoietic compartment could protect the kidney against IRI via preservation of microvascular integrity. Here, we demonstrate that hematopoietic overexpression of miR-126 increases neovascularization of subcutaneously implanted Matrigel plugs in mice. After renal IRI, mice overexpressing miR-126 displayed a marked decrease in urea levels, weight loss, fibrotic markers, and injury markers (such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin). This protective effect was associated with a higher density of the peritubular capillary network in the corticomedullary junction and increased numbers of bone marrow-derived endothelial cells. Hematopoietic overexpression of miR-126 increased the number of circulating Lin(-)/Sca-1(+)/cKit(+) hematopoietic stem and progenitor cells. Additionally, miR-126 overexpression attenuated expression of the chemokine receptor CXCR4 on Lin(-)/Sca-1(+)/cKit(+) cells in the bone marrow and increased renal expression of its ligand stromal cell-derived factor 1, thus favoring mobilization of Lin(-)/Sca-1(+)/cKit(+) cells toward the kidney. Taken together, these results suggest overexpression of miR-126 in the hematopoietic compartment is associated with stromal cell-derived factor 1/CXCR4-dependent vasculogenic progenitor cell mobilization and promotes vascular integrity and supports recovery of the kidney after IRI.
Identifying the Genetic Landscape of Squamous Cell Carcinoma (SCC) and Adenosquamous Carcinoma (ASC) of the Lung Using Next-Generation Sequencing (NGS)
Authors: N. Chilingirova, L. Balabanski, D. Toncheva, G. Kurteva, D. Damyanov, P. Chilingirov
Journal: Annals of Oncology (2015)
Nitric Oxide, a Mediator of Inflammation, Suppresses Tumorigenesis
Authors: S. Perwez Hussain, Glennwood E. Trivers, Lorne J. Hofseth, Peijun He, Irfan Shaikh, Leah E. Mechanic, Saira Doja, Weidong Jiang, Jeffrey Subleski, Lynnette Shorts, Diana Haines, Victor E. Laubach, Robert H. Wiltrout, Draginja Djurickovic, Curtis C. Harris
Journal: Cancer Research (2004)

Abstract Inflammation influences the development of cancer. The nitric oxide synthase (NOS2) is induced by inflammatory cytokines, e.g., tumor necrosis factor α and interleukin 1β, and produces nitric oxide (NO·), a critical mediator of the inflammatory response. Because p53 governs NO· production by transcriptionally transrepressing NOS2, we used a genetic strategy to determine whether NO· and p53 cooperatively regulate tumorigenesis. Lymphomas developed more rapidly in p53−/−NOS2−/− or p53−/−NOS2+/− mice than in p53−/−NOS2+/+ mice that were cross-bred into a &amp;gt;95% C57BL6 background and maintained in a pathogen-free condition. Likewise, sarcomas and lymphomas developed faster in p53+/−NOS2−/− or p53+/−NOS2+/− than in p53+/−NOS2+/+ mice. When compared with the double knockout mice, p53−/−NOS2+/+ mice showed a higher apoptotic index and a decreased proliferation index with an increased expression of death receptor ligands, CD95-L and tumor necrosis factor-related apoptosis-inducing ligand, and the cell cycle checkpoint protein, p21waf1, in the spleen and thymus before tumor development. Furthermore, mice deficient in both p53 and NOS2 produced a high level of anti-inflammatory interleukin 10 when compared with p53-deficient mice. These studies provide genetic and mechanistic evidence that NO· can suppress tumorigenesis.
Cyclin D1 Inhibits Mitochondrial Activity in B Cells
Authors: Guergana Tchakarska, Mikel Roussel, Xavier Troussard, Brigitte Sola
Journal: Cancer Research (2011)

Abstract Cyclin D1 is a cell cycle regulatory protein that acts at the G1-S transition, following its binding to and activation by the cyclin-dependent kinases 4 or 6. Cyclin D1 is absent from the entire B-cell lineage but is present in a large percentage of 2 types of malignant B-cell hemopathy—mantle cell lymphoma and multiple myeloma— suggesting a major role of this protein in the malignancy process. We show here, in an experimental model of cyclin D1 fusion protein transduction in mature B cells, that, cyclin D1 inhibits total mitochondrial activity. Cyclin D1 is localized at the outer mitochondrial membrane, bound to a voltage-dependent anion channel through its central domain, and it competes with hexokinase 2 for binding to this channel. The bound cyclin D1 decreases the supply of ADP, ATP, and metabolites, thereby reducing energy production. This function of cyclin D1 was also reported by others in normal and transformed mammary epithelial cells, suggesting that it may be ubiquitous. Cancer Res; 71(5); 1690–9. ©2011 AACR.
Progestin-Induced Apoptosis in the Macaque Ovarian Epithelium: Differential Regulation of Transforming Growth Factor- 
Authors: G. C. Rodriguez
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Oral contraceptive (OC) use is associated with a reduced risk of ovarian cancer. An OC component, progestin, induces apoptosis in the primate ovarian epithelium. One regulator of apoptosis is transforming growth factor-β (TGF-β). We determined the effect of progestin on TGF-β expression in the primate ovarian epithelium and examined the relationship between TGF-β expression and apoptosis. Methods: Female cynomolgus macaques were randomly assigned to receive a diet for 35 months containing no hormones (n = 20); the OC Triphasil (n = 17); or each of its constituents, ethinyl estradiol (estrogen, n = 20) or levonorgestrel (progestin, n = 18 ), alone. Ovarian sections were immunostained with monoclonal antibodies against TGF-β1 or TGF-β2 plus TGF-β3 (TGF-β2/3) isoforms. The expression of TGF-β isoforms in four ovarian compartments (epithelium, oocytes, granulosa cells, and hilar vascular endothelium) was compared among treatment groups. The association between TGF-β expression and apoptosis, as determined by morphology and histochemistry, was examined in ovarian epithelium. All statistical tests were two-sided. Results: Compared with ovaries from the control and estrogen-only-treated monkeys, the ovaries of progestin-treated monkeys showed 1) a marked decrease in the expression of TGF-β1 and a concomitant increase in the expression of the TGF-β2/3 isoforms in the ovarian epithelium (P<.001), 2) an increase in the expression of TGF-β2/3 in the hilar vascular endothelium (P<.001), and 3) a marked decrease in TGF-β2/3 expression in granulosa cells (P<.001). The apoptotic index of the ovarian epithelium was highly associated with the change in expression from TGF-β1 (P<.001) to TGF-β2/3 (P≤.002) induced by progestin treatment. Conclusions: Progestin induces differential regulation in the ovarian epithelium of TGF-β, a change in the expression of which is highly associated with apoptosis. These data suggest a possible biologic mechanism for the protective association between OC use and reduced ovarian cancer risk.
Risk Factor Modification and Projections of Absolute Breast Cancer Risk
Authors: E. Petracci, A. Decarli, C. Schairer, R. M. Pfeiffer, D. Pee, G. Masala, D. Palli, M. H. Gail
Journal: JNCI Journal of the National Cancer Institute (2011)

Although modifiable risk factors have been included in previous models that estimate or project breast cancer risk, there remains a need to estimate the effects of changes in modifiable risk factors on the absolute risk of breast cancer. Using data from a case–control study of women in Italy (2569 case patients and 2588 control subjects studied from June 1, 1991, to April 1, 1994) and incidence and mortality data from the Florence Registries, we developed a model to predict the absolute risk of breast cancer that included five non-modifiable risk factors (reproductive characteristics, education, occupational activity, family history, and biopsy history) and three modifiable risk factors (alcohol consumption, leisure physical activity, and body mass index). The model was validated using independent data, and the percent risk reduction was calculated in high-risk subgroups identified by use of the Lorenz curve. The model was reasonably well calibrated (ratio of expected to observed cancers = 1.10, 95% confidence interval [CI] = 0.96 to 1.26), but the discriminatory accuracy was modest. The absolute risk reduction from exposure modifications was nearly proportional to the risk before modifying the risk factors and increased with age and risk projection time span. Mean 20-year reductions in absolute risk among women aged 65 years were 1.6% (95% CI = 0.9% to 2.3%) in the entire population, 3.2% (95% CI = 1.8% to 4.8%) among women with a positive family history of breast cancer, and 4.1% (95% CI = 2.5% to 6.8%) among women who accounted for the highest 10% of the total population risk, as determined from the Lorenz curve. These data give perspective on the potential reductions in absolute breast cancer risk from preventative strategies based on lifestyle changes. Our methods are also useful for calculating sample sizes required for trials to test lifestyle interventions.
Lithium Effects on Electrolyte Excretion
Authors: JOE P. TUPIN, GEORGE K. SCHLAGENHAUF, DANIEL L. CRESON
Journal: American Journal of Psychiatry (1968)

Lithium carbonate was administered to normal controls and to manic-depressive patients under carefully controlled conditions. Particular attention was given to diet. The authors found that lithium clearly affects the metabolism of sodium and calcium and, to some extent, magnesium. Minimal affective and behavioral effects of the lithium were noted by the normal controls. There was some suggestion of abnormality in the circadian (24-hour) rhythm of temperature and some other physiological measurements among the manic-depressive group.
Toxoplasmal and Toxocaral Infections: A Clinical Investigation into Their Relationship
Authors: R. A. Wiseman, D. G. Fleck, A. W. Woodruff
Journal: BMJ (1970)

An investigation was carried out to determine whether a relationship existed between infections with Toxoplasma gondii and Toxocara canis. Antibodies were sought by the toxoplasma dye test and the toxocara skin sensitivity test. Sixty-seven patients were examined in the United Kingdom; 38 had positive toxoplasma dye tests, two of these being toxocara-positive; and 29 had negative dye tests, six of them being toxocara-positive. From the total of eight toxocarapositive patients antibodies to toxoplasma were detected in two, an incidence no greater than that expected for a normal population.Sera from 60 toxocara-positive African patients were examined; 20 possessed antibodies to Toxoplasma. Analysis according to age group or geographical location indicated that this incidence was no greater than that expected for patients without evidence of toxocaral infection.This study therefore showed no causal or clinically important relationship between toxoplasmal and toxocaral infections.
Dendritic Cells Regulate Exposure of MHC Class II at Their Plasma Membrane by Oligoubiquitination
Authors: Guillaume van Niel, Richard Wubbolts, Toine ten Broeke, Sonja I. Buschow, Ferry A. Ossendorp, Cornelis J. Melief, Graca Raposo, Bas W. van Balkom, Willem Stoorvogel
Journal: Immunity (2006)
Increased neutrophils and cytokines, TNF-alpha and IL-8, in induced sputum of non-asthmatic patients with chronic dry cough
Authors: A. Jatakanon, U. G Lalloo, S. Lim, K. F. Chung, P. J Barnes
Journal: Thorax (1999)

<h3>BACKGROUND</h3> The pathogenesis of non-asthmatic chronic dry cough remains unclear. <h3>METHODS</h3> A study was undertaken to determine whether airway inflammation could be a contributing factor by analysing inflammatory cells and cytokines in induced sputum from 19 patients with chronic dry cough of varying aetiology, excluding asthma and bronchiectasis, and from 10 normal controls. The associated causes for the chronic cough were post-nasal drip (n = 5), gastro-oesophageal reflux (n = 4), and idiopathic (n = 10). All patients had an enhanced cough reflex to capsaicin. <h3>RESULTS</h3> Sputum neutrophilia (median (interquartile range)) was found in the patients with chronic cough (59.4 (27.1)%) compared with the normal controls (28.4 (22.0)%; p&lt;0.01, 95% CI 11.3 to 42.2). Sputum levels of interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α) were also significantly increased compared with normal controls (0.57 (1.08) and 0.25 (0.72) ng/ml; p&lt;0.05 (95% CI 0.05 to 1.75) for IL-8; 48.3 (34.4) and 12.6 (33.6) pg/ml, p&lt;0.01 (95% CI 8.8 to 69.8) for TNF-α). <h3>CONCLUSION</h3> Neutrophils and cytokines associated with neutrophil chemotaxis and activation may contribute to the pathogenesis of non-asthmatic chronic dry cough.
Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury
Authors: Tom Luedde, Ulrike Assmus, Torsten Wüstefeld, Andreas Meyer zu Vilsendorf, Tania Roskams, Mark Schmidt-Supprian, Klaus Rajewsky, David A. Brenner, Michael P. Manns, Manolis Pasparakis, Christian Trautwein
Journal: Journal of Clinical Investigation (2005)

The inhibitor of NF-κB (I-κB) kinase (IKK) complex consists of 3 subunits, IKK1, IKK2, and NF-κB essential modulator (NEMO), and is involved in the activation of NF-κB by various stimuli. IKK2 or NEMO constitutive knockout mice die during embryogenesis as a result of massive hepatic apoptosis. Therefore, we examined the role of IKK2 in TNF-induced apoptosis and ischemia/reperfusion (I/R) injury in the liver by using conditional knockout mice. Hepatocyte-specific ablation of IKK2 did not lead to impaired activation of NF-κB or increased apoptosis after TNF-α stimulation whereas conditional NEMO knockout resulted in complete block of NF-κB activation and massive hepatocyte apoptosis. In a model of partial hepatic I/R injury, mice lacking IKK2 in hepatocytes displayed significantly reduced liver necrosis and inflammation than wild-type mice. AS602868, a novel chemical inhibitor of IKK2, protected mice from liver injury due to I/R without sensitizing them toward TNF-induced apoptosis and could therefore emerge as a new pharmacological therapy for liver resection, hemorrhagic shock, or transplantation surgery.
ATP-Binding Cassette Transporter A1 Modulates Apolipoprotein A-I Transcytosis Through Aortic Endothelial Cells
Authors: Clara Cavelier, Lucia Rohrer, Arnold von Eckardstein
Journal: Circulation Research (2006)

High-density lipoproteins and their major protein constituent apolipoprotein A-I (apoA-I) possess diverse atheroprotective properties. Most of them must be exerted within the arterial wall. Actually, high-density lipoproteins are the most abundant lipoproteins within the arterial intima. We have recently reported that apoA-I is transcytosed through aortic endothelial cells. In the present study, we evaluate the role of ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor BI (SR-BI) in this process. Using pharmacological interventions and RNA interference, we investigated whether ABCA1 and SR-BI modulate apoA-I binding, internalization and transcytosis in endothelial cells. Upregulation of ABCA1 with oxysterols increased apoA-I binding and internalization. Trapping ABCA1 on the cell surface with cyclosporin A enhanced apoA-I binding but decreased its internalization and transcytosis. In addition, apoA-I binding, internalization, and transcytosis were reduced by at least 50% after silencing ABCA1 but not after knocking down SR-BI. The integrity of the endothelial cell monolayer was affected neither by cyclosporin A treatment nor by ABCA1 silencing, as controlled by measuring inulin permeability. Finally, in ABCA1-GFP–expressing cells, fluorescently labeled apoA-I colocalized intracellularly with ABCA1-GFP. However, apoA-I–containing vesicles did not colocalize with the late endosome marker LAMP-1 (lysosome-associated membrane protein-1). In conclusion, ABCA1, but not SR-BI, modulates the transcytosis of apoA-I through endothelial cells.