tbuckley/cabot-search huggingface dataset:
Urinary Metabolites of Organophosphate Flame Retardants: Temporal Variability and Correlations with House Dust Concentrations
Authors: John D. Meeker, Ellen M. Cooper, Heather M. Stapleton, Russ Hauser
Journal: Environmental Health Perspectives (2013)

A reduction in the use of polybrominated diphenyl ethers (PBDEs) because of human health concerns may result in an increased use of and human exposure to organophosphate flame retardants (OPFRs). Human exposure and health studies of OPFRs are lacking.We sought to define the degree of temporal variability in urinary OPFR metabolites in order to inform epidemiologic study design, and to explore a potential primary source of exposure by examining the relationship between OPFRs in house dust and their metabolites in urine.Nine repeated urine samples were collected from 7 men over the course of 3 months and analyzed for bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate (DPP), metabolites of the OPFRs tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP), respectively. Intraclass correlation coefficients (ICCs) were calculated to characterize temporal reliability. Paired house dust and urine samples were collected from 45 men.BDCPP was detected in 91% of urine samples, and DPP in 96%. Urinary BDCPP showed moderate-to-strong temporal reliability (ICC range, 0.55-0.72). ICCs for DPP were lower, but moderately reliable (range, 0.35-0.51). There was a weak [Spearman r (r(S)) = 0.31] but significant (p = 0.03) correlation between urinary BDCPP and TDCPP concentrations in house dust that strengthened when nondetects (r(S) = 0.47) were excluded. There was no correlation between uncorrected DPP and TPP measured in house dust (r(S) < 0.1).Household dust may be an important source of exposure to TDCPP but not TPP. Urinary concentrations of BDCPP and DPP were moderately to highly reliable within individuals over 3 months.
Association of TNF2, a TNF-α Promoter Polymorphism, With Septic Shock Susceptibility and Mortality
Authors: Jean-Paul Mira, Alain Cariou, Franck Grall, Christophe Delclaux, Marie-Reine Losser, Fahrad Heshmati, Christine Cheval, Mehran Monchi, Jean-Louis Teboul, Florence Riché, Ghislaine Leleu, Laurence Arbibe, Alexandre Mignon, Marc Delpech, Jean-François Dhainaut
Journal: JAMA (1999)

THE PRIMARY cause of death in intensive care units (ICUs).With a mortality rate in excess of 50%, it results in more than 100 000 deaths a year in the United States. 1,2Sepsis-induced organ failure leading to death appears to be due to the activation of a mediator cascade initiated by microbial components. 1,2Although the pathophysiology of systemic inflammation and organ dysfunction is complex, tumor necrosis factor alpha (TNF-␣) has emerged as a proximal and central cytokine of septic shock. 2,3Its administration reproduces essentially all the deleterious effects of endotoxin and bacteria, including
Heterogeneous Ribonucleoprotein K and Thymidine Phosphorylase Are Independent Prognostic and Therapeutic Markers for Nasopharyngeal Carcinoma
Authors: Lih-Chyang Chen, Chuen Hsueh, Ngan-Ming Tsang, Ying Liang, Kai-Ping Chang, Sheng-Po Hao, Jau-Song Yu, Yu-Sun Chang
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Heterogeneous ribonucleoprotein K (hnRNP K) regulates thymidine phosphorylase (TP) mRNA stability. The aim of the present study was to analyze hnRNP K and TP expression in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic and therapeutic potential of these two markers. Experimental Design: We analyzed hnRNP K and TP expression immunohistochemically in 121 clinically proven NPC cases. Statistical analyses were applied to correlate cytoplasmic hnRNP K with elevated TP expression and determine the prognostic significance of these parameters. The therapeutic implication of elevated TP expression was determined by measuring sensitivity of NPC cells to the TP-targeting drug, 5-fluoro-5′-deoxyuridine (5′-DFUR). Results: There was a high correlation between cytoplasmic hnRNP K and high TP (P &amp;lt; 0.001). Both cytoplasmic hnRNP K and high TP were associated with poor overall survival (OS; P = 0.007 and P &amp;lt; 0.001, respectively) and distant metastasis-free survival (P = 0.003 and 0.001, respectively) of NPC patients. A multivariate analysis confirmed that both cytoplasmic hnRNP K and high TP are independent prognostic predictors for OS (P = 0.020 and 0.010, respectively). NPC cells expressing high TP were more sensitive to treatment with the TP-targeting drug, 5′-DFUR. Conclusions: Cytoplasmic hnRNP K and high TP are associated with shorter OS and distant metastasis-free survival in NPC patients. In vitro experiments suggest that NPC tumors with high TP expression may be sensitive to 5′-DFUR treatment. Cytoplasmic hnRNP K and high TP may be potential prognostic and therapeutic markers for NPC, but additional validation studies are warranted.
Safety and Antithrombotic Efficacy of Moderate Platelet Count Reduction by Thrombopoietin Inhibition in Primates
Authors: Erik I. Tucker, Ulla M. Marzec, Michelle A. Berny, Sawan Hurst, Stuart Bunting, Owen J. T. McCarty, András Gruber, Stephen R. Hanson
Journal: Science Translational Medicine (2010)

Most heart attacks and strokes are caused by blood clots (thrombi) that block the vasculature. Because disease-causing arterial thrombosis depends on blood platelets, platelet inhibitors such as aspirin and clopidogrel effectively decrease the risk of thrombosis; however, they also impair platelet-dependent hemostasis that staunches bleeding from wounds and can therefore produce excessive bleeding. Experimental studies show that a reduction in the number of platelets also inhibits thrombosis, but these treatments also interfere with platelet function. Because normal hemostasis requires that the platelet concentration remain within a physiological range in the circulation, we evaluated whether lowering the number of circulating platelets--but only to a value still within the normal range--by inhibiting platelet formation in the bone marrow inhibits acute thrombogenesis in baboons. We reduced the platelet count with an inhibitor against the megakaryocyte-promoting hormone thrombopoietin and then showed that experimental occlusive thrombogenesis on collagen-coated vascular grafts was reduced, without impairment of primary hemostasis. These results suggest that suppressing platelet production without interfering with the hemostatic function of platelets may offer a safe alternative to current therapies for prevention of stroke and heart attack triggered by blood clotting.
Noninvasive visualization of the dilated main coronary arteries in coronary artery fistulas by cross-sectional echocardiography.
Authors: J Yoshikawa, H Katao, K Yanagihara, Y Takagi, F Okumachi, K Yoshida, Y Tomita, T Fukaya, K Baba
Journal: Circulation (1982)

Real-time cross-sectional echocardiographic studies of the main coronary arteries were performed in 20 normal subjects, 12 patients with patent ductus arteriosus and 14 patients with coronary artery fistula in whom the diagnosis was established by angiography. In 12 patients, the coronary artery that formed the fistula was dilated: The right coronary artery was involved in eight and the left coronary artery in four. The dilated coronary artery appeared as two dominant parallel echoes of wide lumen originating from the aorta in the region of the involved artery. Th echo diameter of the coronary artery correlated well with the angiographically estimated diameter of the artery. In the normal subjects and the patients with patent ductus arteriosus, we found no echocardiographic findings of coronary artery dilatation. This study demonstrates that cross-sectional echocardiography is useful in identifying the dilated coronary artery in coronary artery fistula and distinguishing this entity from patent ductus arteriosus.
Gallbladder emptying stimuli in obese and normal-weight subjects
Authors: Bradford G. Stone, Howard J. Ansel, Francis J. Peterson, Roger L. Gebhard
Journal: Hepatology (1992)

ABSTRPlCT Gallbladder stasis may be an important factor in the pathogenesis of cholesterol–gallstone formation in some individuals. We investigated gallbladder function in a group of nondieting, gallstone–free, healthy subjects with normal (22 ± 1 kg/m 2 ) and high (36 ± 1 kg/m 2 ) body mass indexes. Fasting gallbladder volume (28.2 ± 4.4 ml) and residual volume after maximal emptying (8.4 ± 2.3 ml) in high-body–mass index subjects were not significantly different from those of normal-body–mass index subjects (20.5 ± 2.5 ml and 4.2 ± 1.3 ml, respectively). The percentage of gallbladder emptying (71% ± 5%) and the rate of gallbladder emptying (–1.9 ± 0.3 × 10 -2 min -1 ) in high-body–mass index subjects in response to a maximal emptying stimulus was similar to the percentage of emptying (78% ± 6%) and rate of emptying (-2.3 ± 0.6 × 10 -2 min -1 ) in normal-body–mass index subjects. A liquid meal containing less than 1 gm fat, 14 gm protein and 6 gm carbohydrate resulted in both a decreased rate of gallbladder emptying and an increased residual gallbladder emptying and an increased residual gallbladder volume in both groups. The addition of 10 or 20 gm (but not 4 gm) of fat to the liquid meal restored gallbladder emptying to the maximal–stimulus level. These results demonstrate that gallbladder emptying in response to a single liquid meal stimulus is not altered in obesity and that dose–response relationships to fat are similar in obese and normal–weight individuals. Furthermore, these findings suggest that a threshold quantity of fat-no more than 10 gm-included in a liquid–meal stimulus might be able to restore gallbladder emptying to normal. It does not appear that an intrinsic defect in gallbladder contractility is responsible for the increased incidence of gallstones in obesity. (Hepatology 1992;15:795-798).
Long-term outcome and late effects in patients transplanted with mobilised blood or bone marrow: a randomised trial
Authors: Birte Friedrichs, André Tichelli, Andrea Bacigalupo, Nigel H Russell, Tapani Ruutu, Michael Y Shapira, Meral Beksac, Dirk Hasenclever, Gérard Socié, Norbert Schmitz
Journal: The Lancet Oncology (2010)
Molecular Pathways: Beta-Adrenergic Signaling in Cancer
Authors: Steven W. Cole, Anil K. Sood
Journal: Clinical Cancer Research (2011)

Beta-adrenergic signaling has been found to regulate multiple cellular processes that contribute to the initiation and progression of cancer, including inflammation, angiogenesis, apoptosis/anoikis, cell motility and trafficking, activation of tumor-associated viruses, DNA damage repair, cellular immune response, and epithelial-mesenchymal transition. In several experimental cancer models, activation of the sympathetic nervous system promotes the metastasis of solid epithelial tumors and the dissemination of hematopoietic malignancies via β-adrenoreceptor-mediated activation of protein kinase A and exchange protein activated by adenylyl cyclase signaling pathways. Within the tumor microenvironment, β-adrenergic receptors on tumor and stromal cells are activated by catecholamines from local sympathetic nerve fibers (norepinephrine) and circulating blood (epinephrine). Tumor-associated macrophages are emerging as key targets of β-adrenergic regulation in several cancer contexts. Sympathetic nervous system regulation of cancer cell biology and the tumor microenvironment has clarified the molecular basis for long-suspected relationships between stress and cancer progression, and now suggests a highly leveraged target for therapeutic intervention. Epidemiologic studies have linked the use of β-blockers to reduced rates of progression for several solid tumors, and preclinical pharmacologic and biomarker studies are now laying the groundwork for translation of β-blockade as a novel adjuvant to existing therapeutic strategies in clinical oncology.
15-Hydroxyprostaglandin Dehydrogenase Is Down-regulated in Gastric Cancer
Authors: Alexandra Thiel, Aparna Ganesan, Johanna Mrena, Siina Junnila, Antti Nykänen, Annabrita Hemmes, Hsin-Hsiung Tai, Outi Monni, Arto Kokkola, Caj Haglund, Tatiana V. Petrova, Ari Ristimäki
Journal: Clinical Cancer Research (2009)

We have investigated the expression and regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in gastric cancer.Clinical gastric adenocarcinoma samples were analyzed by immunohistochemistry and quantitative real-time PCR for protein and mRNA expression of 15-PGDH and for methylation status of 15-PGDH promoter. The effects of interleukin-1beta (IL-1beta) and epigenetic mechanisms on 15-PGDH regulation were assessed in gastric cancer cell lines.In a gastric cancer cell line with a very low 15-PGDH expression (TMK-1), the 15-PGDH promoter was methylated and treatment with a demethylating agent 5-aza-2'-deoxycytidine restored 15-PGDH expression. In a cell line with a relatively high basal level of 15-PGDH (MKN-28), IL-1beta repressed expression of 15-PGDH mRNA and protein. This effect of IL-1beta was at least in part attributed to inhibition of 15-PGDH promoter activity. SiRNA-mediated knockdown of 15-PGDH resulted in strong increase of prostaglandin E(2) production in MKN-28 cells and increased cell growth of these cells by 31% in anchorage-independent conditions. In clinical gastric adenocarcinoma specimens, 15-PGDH mRNA levels were 5-fold lower in gastric cancer samples when compared with paired nonneoplastic tissues (n = 26) and 15-PGDH protein was lost in 65% of gastric adenocarcinomas (n = 210).15-PGDH is down-regulated in gastric cancer, which could potentially lead to accelerated tumor progression. Importantly, our data indicate that a proinflammatory cytokine linked to gastric carcinogenesis, IL-1beta, suppresses 15-PGDH expression at least partially by inhibiting promoter activity of the 15-PGDH gene.
Cyclin A Downregulation and p21 <sup>cip1</sup> Upregulation Correlate With GATA-6–Induced Growth Arrest in Glomerular Mesangial Cells
Authors: Daisuke Nagata, Etsu Suzuki, Hiroaki Nishimatsu, Masao Yoshizumi, Toshiaki Mano, Kenneth Walsh, Masataka Sata, Masao Kakoki, Atsuo Goto, Masao Omata, Yasunobu Hirata
Journal: Circulation Research (2000)

Abstract —The GATA-6 transcription factor is reported to be expressed in vascular myocytes. Because glomerular mesangial cells (GMCs) and vascular myocytes have similar properties, we examined whether GATA-6 was expressed in cultured GMCs and whether overexpression of GATA-6 induced cell cycle arrest in GMCs, using a recombinant adenovirus that expresses GATA-6 (Ad GATA-6). GATA-6 expression in GMCs was downregulated when quiescent GMCs were stimulated by serum to reenter the cell cycle. [ 3 H]thymidine uptake was inhibited in GMCs infected with Ad GATA-6 in a dose- and time-dependent manner. The expression of cyclin A protein was decreased and that of the cyclin-dependent kinase inhibitor p21 cip1 was increased in GMCs infected with Ad GATA-6. Although the expression of p21 cip1 transcripts did not change remarkably, p21 cip1 protein was stabilized in GMCs infected with Ad GATA-6, suggesting a post-transcriptional regulation of p21 cip1 expression. Northern blot analysis showed that expression of the cyclin A transcript was decreased in Ad GATA-6–infected cells, whereas this decrease of cyclin A was not observed in GMCs derived from p21 cip1 null mice. Our results demonstrate that GATA-6 is endogenously expressed in GMCs and that overexpression of GATA-6 can induce cell cycle arrest. Our results also show that GATA-6–induced cell cycle arrest is associated with inhibition of cyclin A expression and p21 cip1 upregulation. Finally, our results indicate that the GATA-6–induced suppression of cyclin A expression depends on the presence of p21 cip1 .
Transforming growth factor-beta1 in sarcoidosis
Authors: F Salez, P Gosset, MC Copin, C Lamblin Degros, AB Tonnel, B Wallaert
Journal: European Respiratory Journal (1998)

Transforming growth factor-beta (TGF-beta) is a cytokine that promotes extracellular matrix accumulation and inhibits matrix degradation. Although the natural course of sarcoidosis is usually favourable, granuloma healing in the lung may result in pulmonary fibrosis and respiratory impairment in some patients. In this study TGF-beta1 was evaluated in bronchoalveolar lavage (BAL) fluid and culture supernatants of alveolar macrophages (AM) from 73 patients with biopsy-proven sarcoidosis. Disease activity was defined when patients recently developed or increased symptoms (cough, dyspnoea, systemic symptoms) and/or demonstrated increasing opacities on chest radiography. Pulmonary function tests were performed in all patients including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC) and the diffusing capacity of the lung for carbon monoxide (DL,CO). Fourteen patients with idiopathic pulmonary fibrosis (IPF) and 14 healthy subjects were investigated as a control group. Immunohistochemistry was used to evaluate the cell distribution of TGF-beta1 on lung specimens. TGF-beta1 levels in BAL and in AM supernatants were not different between sarcoidosis and healthy subjects, whereas they were markedly increased in IPF. However, the TGF-beta1 level was significantly increased in BAL fluid but not in AM supernatants from sarcoidosis with altered lung function, compared with patients with normal lung function. The TGF-beta1 level in BAL was increased in active sarcoidosis but this increased level was mainly related to the higher level observed in patients with altered lung function. TGF-beta1 levels in BAL correlated significantly with the lymphocyte percentage. TGF-beta1 staining assessed by immunohistochemistry was intense in epithelioid histiocytes comprising non-necrotizing granuloma and in bronchiolar epithelial cells, in hyperplastic type II pneumocytes and occasionally in AM. This study supports the hypothesis that overproduction of transforming growth factor-beta1 is associated with functional impairment in patients with pulmonary sarcoidosis.
STRONG ASSOCIATION BETWEEN IDIOPATHIC MEMBRANOUS NEPHROPATHY AND HLA-DRW3.
Authors: P.T. Klouda, E.J. Acheson, F.S. Goldby, W. Lawler, J. Manos, P.A. Dyer, R. Harris, N.P. Mallick, G. Williams
Journal: The Lancet (1979)
Twelve weeks of follow-up is sufficient for the determination of sustained virologic response in patients treated with interferon α for chronic hepatitis C
Authors: Stefan Zeuzem, E.Jenny Heathcote, Mitchell L Shiffman, Teresa L Wright, Vincent G Bain, Morris Sherman, S.Victor Feinman, Michael W Fried, Jens Rasenack, Christoph Sarrazin, Donald M Jensen, Amy Lin, Joseph H Hoffman, Farhad Sedarati
Journal: Journal of Hepatology (2003)
Three-Year Outcome After Coronary Stenting Versus Bypass Surgery for the Treatment of Multivessel Disease
Authors: Victor M.G. Legrand, Patrick W. Serruys, Felix Unger, Ben A. van Hout, Mathias C.M. Vrolix, Geert M.P. Fransen, Torsten Toftegaard Nielsen, Peter Kildeberg Paulsen, Ricardo Seabra Gomes, João M.G. de Queiroz e Melo, José P. Marques dos Santos Neves, Wietze Lindeboom, Bianca Backx
Journal: Circulation (2004)

The primary results of Arterial Revascularization Therapy Study reported a greater need for repeated revascularization after percutaneous coronary intervention with stenting (PCI). However, PCI was less expensive than coronary artery bypass grafting (CABG) and offered the same degree of protection against death, stroke, and myocardial infarction.Patients with multivessel disease (n=1205) were randomly assigned to either CABG or PCI and followed up for up to 3 years. Survival rates without stroke or myocardial infarction were similar in each group at 1 year and 3 years (90.5% versus 91.4% for PCI versus CABG at 1 year and 87.2% versus 88.4% for PCI versus CABG at 3 years). However, the respective repeat revascularization rates were 21.2% and 26.7% at 1 and 3 years in patients allocated to PCI, compared with 3.8% and 6.6% in patients allocated to CABG (P<0.0001). Diabetes (P<0.0009) and maximal pressure for stent deployment (P<0.002) are the strongest independent predictors of events at 3 years after PCI, whereas left anterior descending coronary artery grafting (P<0.006) is the best predictor of event-free survival at 3 years after CABG. The incremental cost of surgery compared with PCI for an event-free patient was 19 257 at 1 year but decreased to 10 492 at 3 years. It remained at 142 391 at 3 years when revascularization procedures were excluded in the efficacy end point, however.Three-year survival rates without stroke and myocardial infarction are identical in both groups, and the cost/benefit ratio of stenting is determined primarily by the increasing need for revascularization in the PCI group.
Adenovirus-Mediated Local Expression of Human Tissue Factor Pathway Inhibitor Eliminates Shear Stress–Induced Recurrent Thrombosis in the Injured Carotid Artery of the Rabbit
Authors: Takahiro Nishida, Hikaru Ueno, Nobuhiko Atsuchi, Ryuji Kawano, Yujiro Asada, Yo Nakahara, Yu-ichi Kamikubo, Akira Takeshita, Hisataka Yasui
Journal: Circulation Research (1999)

Abstract —The main cause of acute coronary syndrome may be recurrent thrombosis, which is initiated by the activation of the extrinsic coagulation pathway. Tissue factor (TF) pathway inhibitor (TFPI) efficiently inhibits an early step in this pathway by the formation of a complex with factor VIIa, TF, and factor Xa. We determined whether local TFPI gene transfer can inhibit thrombosis in an injured artery without inducing systemic side effects. Balloon-injured rabbit carotid arteries were infected with an adenoviral vector that expressed either human TFPI (AdCATFPI) or bacterial β-galactosidase (AdCALacZ). Two to 6 days after gene transfer, thrombosis was induced by the production of constant stenosis of the artery, and blood flow was measured continuously with an electromagnetic flow probe. A cyclic flow variation, which is thought to reflect the recurrent formation and dislodgment of mural thrombi, was observed in all AdCALacZ-infected arteries as well as in saline-infused arteries. In contrast, no cyclic flow variation was detectable in AdCATFPI-transfected arteries, even in the presence of epinephrine (1 μg · kg −1 · min −1 infusion). Prothrombin time, activated partial thromboplastin time, and the ex vivo platelet aggregation induced by either adenosine diphosphate or collagen were unaltered in AdCATFPI-infected rabbits. We found that in vivo TFPI gene transfer into an injured artery completely inhibits the recurrent thrombosis induced by shear stress even in the presence of catecholamine, without affecting systemic coagulation status. Adenovirus-mediated local expression of TFPI may have the potential for the treatment of human thrombosis.