tbuckley/cabot-search huggingface dataset:
Improvement of Endothelial Function by Systemic Transfusion of Vascular Progenitor Cells
Authors: Sven Wassmann, Nikos Werner, Thomas Czech, Georg Nickenig
Journal: Circulation Research (2006)

Endothelial dysfunction is characterized by abnormalities in vasoreactivity and is a marker of the extent of atherosclerosis. Cellular repair by circulating progenitor cells of ongoing vascular injury may be essential for vascular integrity and function and may limit abnormalities in vasoreactivity. Apolipoprotein E–deficient (apoE −/− ) mice were splenectomized and treated with high-cholesterol diet for 5 weeks, resulting in marked impairment of endothelium-dependent vasodilation of aortic segments as compared with wild-type mice. Intravenous transfusion of 2×10 7 spleen-derived mononuclear cells (MNCs) isolated from wild-type mice on 3 consecutive days restored endothelium-dependent vasodilation in the apoE −/− mice, as measured 7, 14, and 45 days after transfusion. Histological analyses of aortic tissue identified fluorescent-labeled, exogenously applied progenitor cells that expressed the endothelial cell marker CD31 in the endothelial cell layer of atherosclerotic lesions. Progenitor cell treatment led to increased vascular nitric oxide synthase activity. Transfusion of either in vitro-differentiated Dil-Ac-LDL/lectin-positive endothelial progenitor cells, CD11b-positive (monocyte marker), CD45R-positive (B-cell marker), or Sca-1–positive (stem cell marker) MNC subpopulations significantly improved endothelium-dependent vasodilation, although these treatments were not as effective as transfusion of total MNCs. Depletion of MNCs of either CD11b-positive, CD45R-positive, or Sca-1–positive cells resulted in significant attenuation of endothelium-dependent vasodilation as compared with nondepleted MNCs; however, vasoreactivity was still significantly improved as compared with saline-treated apoE −/− mice. Intravenous transfusion of spleen-derived MNCs improves endothelium-dependent vasodilation in atherosclerotic apoE −/− mice, indicating an important role of circulating progenitor cells for the repair of ongoing vascular injury. More than 1 subpopulation of the MNC fraction seems to be involved in this effect.
Inhaled NO and almitrine bismesylate in patients with acute respiratory distress syndrome: effect of noradrenalin
Authors: L Papazian, F Bregeon, F Gaillat, X Thirion, A Roch, E Cortes, V Fulachier, P Saux, Y Jammes, JP Auffray
Journal: European Respiratory Journal (1999)

The combination of inhaled nitric oxide with almitrine bismesylate has been proposed for the management of acute respiratory distress syndrome in order to divert pulmonary blood flow away from poorly ventilated toward well-ventilated areas. The aims of this prospective and comparative study were to: 1) confirm the beneficial effects on oxygenation of this association; 2) evaluate the haemodynamic effects of this association; and 3) evaluate the influence of noradrenaline (a nonspecific vasoconstrictor) on the modification of gas exchange related to inhaled NO and/or almitrine bismesylate. Forty-one sedated paralysed and ventilated patients were investigated. Haemodynamic and blood gas measurements were performed in a fixed order: baseline; inhalation of NO for 30 min.; intravenous infusion of almitrine bismesylate; and concomitant administration of inhaled NO and almitrine bismesylate. Inhaled NO and almitrine bismesylate increased arterial oxygen tension (Pa,O2)/inspiratory oxygen fraction (FI,O2) (p&lt;0.001). The association of inhaled NO with almitrine bismesylate resulted in a dramatic improvement in Pa,O2/FI,O2 (p&lt;0.0001 versus almitrine bismesylate, p&lt;0.05 versus inhaled NO). In patients receiving noradrenalin (n = 19), almitrine bismesylate had no effect on oxygenation. The present study confirmed that the combination of inhaled NO with almitrine bismesylate improved oxygenation, and demonstrated that almitrine bismesylate has no effect on oxygenation in patients receiving noradrenalin.
Intractable Nausea and Vomiting From Autoantibodies Against a Brain Water Channel
Authors: Raffaele Iorio, Claudia F Lucchinetti, Vanda A Lennon, Gianrico Farrugia, Pankaj J Pasricha, Brian G Weinshenker, Sean J Pittock
Journal: Clinical Gastroenterology and Hepatology (2012)
Continuous fetal monitoring in the ambulant patient.
Authors: T E Torbet, M B Cooke
Journal: BMJ (1976)

reported to arrest haemorrhage from oesophageal varices in a proportion of cases for periods ranging from hours to months,' --6 but haemorrhage recurred in some patients when the cannula was removed.2 46The effectiveness of thoracic duct cannulation for bleeding oesophageal varices is still a controversial, matter.In spite of this, I think that the policy that should be adopted is to perform cannulation of the thoracic duct in patients not fit for major emergency operation.If this minor palliative procedure succeeds in preventing further bleeding the patient can be better prepared for a portacaval shunt operation that can be conducted a few days after his general condition has improved.
Long term study of the effect of sodium cromoglycate on non-specific bronchial hyperresponsiveness.
Authors: C J Jenkins, A B Breslin
Journal: Thorax (1987)

A double blind, crossover study was undertaken to determine whether non-specific hyperresponsiveness in subjects with asthma was reduced by long term treatment with sodium cromoglycate and, if so, whether this was related to change in lung function. Forty four adult asthmatic subjects (41 atopic, three non-atopic) entered the one year study at intervals staggered over six months. After a baseline period to ensure that asthma control was stable subjects entered the treatment period, during which they inhaled sodium cromoglycate 20 mg four times daily or matching placebo four times daily for 16 weeks each, in random order. Response was assessed at four weekly intervals by measurement of lung function and histamine inhalation tests, from which the provocative concentration of histamine causing a 20% fall in FEV1 (PC20H) was calculated. The assessment included daily symptom score, morning and evening Airflow-meter readings and treatment; mean values for each treatment period and also for the final four weeks of each period were compared. There were no significant differences between placebo and sodium cromoglycate treatment for PC20H, FEV1, morning or evening flow meter readings, bronchodilator usage, or symptom scores for the group as a whole, for the 16 week period or for the final four weeks of each period. Thirteen subjects showed better morning and evening flow meter readings while taking sodium cromoglycate than while taking placebo and eight better readings with placebo than with sodium cromoglycate (p less than 0.05). Improvement in lung function did not correlate with baseline lung function or baseline PC20H, or with features of atopy. These results suggest that long term sodium cromoglycate treatment does not alter non-specific bronchial responsiveness in adult asthmatic subjects.
Effect of improved tuberculosis screening and isoniazid preventive therapy on incidence of tuberculosis and death in patients with HIV in clinics in Rio de Janeiro, Brazil: a stepped wedge, cluster-randomised trial
Authors: Betina Durovni, Valeria Saraceni, Lawrence H Moulton, Antonio G Pacheco, Solange C Cavalcante, Bonnie S King, Silvia Cohn, Anne Efron, Richard E Chaisson, Jonathan E Golub
Journal: The Lancet Infectious Diseases (2013)
Thromboxane A2 is a key regulator of pathogenesis during <i>Trypanosoma cruzi</i> infection
Authors: Anthony W. Ashton, Shankar Mukherjee, FNU Nagajyothi, Huan Huang, Vicki L. Braunstein, Mahalia S. Desruisseaux, Stephen M. Factor, Lillie Lopez, Joan W. Berman, Murray Wittner, Philipp E. Scherer, Valerie Capra, Thomas M. Coffman, Charles N. Serhan, Katherine Gotlinger, Kenneth K. Wu, Louis M. Weiss, Herbert B. Tanowitz
Journal: The Journal of Experimental Medicine (2007)

Chagas' disease is caused by infection with the parasite Trypanosoma cruzi. We report that infected, but not uninfected, human endothelial cells (ECs) released thromboxane A2 (TXA2). Physical chromatography and liquid chromatography-tandem mass spectrometry revealed that TXA2 is the predominant eicosanoid present in all life stages of T. cruzi. Parasite-derived TXA2 accounts for up to 90% of the circulating levels of TXA2 in infected wild-type mice, and perturbs host physiology. Mice in which the gene for the TXA2 receptor (TP) has been deleted, exhibited higher mortality and more severe cardiac pathology and parasitism (fourfold) than WT mice after infection. Conversely, deletion of the TXA2 synthase gene had no effect on survival or disease severity. TP expression on somatic cells, but not cells involved in either acquired or innate immunity, was the primary determinant of disease progression. The higher intracellular parasitism observed in TP-null ECs was ablated upon restoration of TP expression. We conclude that the host response to parasite-derived TXA2 in T. cruzi infection is possibly an important determinant of mortality and parasitism. A deeper understanding of the role of TXA2 may result in novel therapeutic targets for a disease with limited treatment options.
Free-Living Physical Activity Energy Expenditure Is Strongly Related to Glucose Intolerance in Cameroonian Adults Independently of Obesity
Authors: Felix K. Assah, Ulf Ekelund, Soren Brage, Jean Claude Mbanya, Nicholas J. Wareham
Journal: Diabetes Care (2008)

We examined the cross-sectional association between objectively measured free-living physical activity energy expenditure (PAEE) and glucose tolerance in adult Cameroonians without known diabetes.PAEE was measured in 34 volunteers using the doubly labeled water method and indirect calorimetry (resting). Fasting blood glucose and 2-h postload blood glucose were measured during a standard 75-g oral glucose tolerance test.There was a significant negative correlation between PAEE and 2-h glucose (r = -0.43; P = 0.01) but not fasting glucose (r = 0.1; P = 0.57). The inverse association between PAEE and 2-h glucose remained after adjustment for age, sex, smoking, alcohol consumption, and BMI (beta = -0.017 [95% CI -0.033 to -0.002]) and was unchanged after further adjustment for waist circumference, body fat percentage, or aerobic fitness.PAEE is inversely associated with 2-h glucose independently of adiposity or fitness. Interventions aimed at increasing PAEE could play an important role in diabetes prevention in developing countries.
Hyperinsulinemia Predicts Fatal Liver Cancer but Is Inversely Associated With Fatal Cancer at Some Other Sites
Authors: Beverley Balkau, Henry S. Kahn, Dominique Courbon, Eveline Eschwège, Pierre Ducimetière
Journal: Diabetes Care (2001)

OBJECTIVE—To investigate whether insulin is a risk factor for death by site-specific cancers. RESEARCH DESIGN AND METHODS—This was a prospective cohort study of 6,237 nondiabetic French working men between ages 44 and 55 years at baseline from the Paris Prospective Study cohort. Death by site-specific cancers was investigated in relation to baseline insulin concentrations during fasting and 2 h after a 75-g oral glucose tolerance test. RESULTS—Of the original 6,237 men in the cohort, 1,739 died over the 23.8 years of follow-up, 778 (45%) from cancer. Baseline hyperinsulinemia, both fasting and 2-h, was significantly associated with fatal liver cancer, with age-adjusted standardized hazards ratios of 2.72 (95% CI 1.87–3.94) and 3.41 (2.23–5.21). In contrast, fasting hyperinsulinemia was inversely associated with fatal lip, oral cavity, and pharynx cancer and larynx cancer, with hazards ratios of 0.55 (0.41–0.75) and 0.63 (0.47–0.83), respectively; 2-h insulin concentrations were inversely associated with stomach and larynx cancers (hazards ratios 0.62 [0.43–0.90] and 0.66 [0.50–0.89], respectively). These relationships were stable after adjusting for other risk factors. Insulin concentrations remained negatively associated with deaths from these cancers in analyses restricted to men who smoked and in those who were not chronic alcohol consumers. CONCLUSIONS—Peripheral hyperinsulinemia, indicative of very high portal insulin concentrations, predicted fatal liver cancer in these nondiabetic men, but was inversely associated with fatal lip, oral cavity, and pharynx cancer; stomach cancer; and larynx cancer.
Evolutionary Origin and Maintenance of Coexpressed Gene Clusters in Mammals
Authors: Marie Sémon, Laurent Duret
Journal: Molecular Biology and Evolution (2006)

Gene order is not random with regard to gene expression in mammals: coexpressed genes, and in particular housekeeping genes, are clustered along chromosomes more often than expected by chance. To understand the origin of these clusters and to quantify the impact of this phenomenon on genome organization, we analyzed clusters of coexpressed genes in the human and mouse genomes. We show that neighboring genes experience continuous concerted expression changes during evolution, which leads to the formation of coexpressed gene clusters. The pattern of expression within these clusters evolves more slowly than the genomic average. Moreover, by studying gene order evolution, we show that some clusters are maintained by natural selection and, therefore, have a functional significance. However, we also demonstrate that some coexpressed gene clusters are the result of neutral coevolution effects, as illustrated by the clustering of genes escaping inactivation on the X chromosome. Moreover, we show that, although statistically significant, constraints on gene orders have a limited impact on mammalian genome organization, affecting only 3–5% of the pool of human and murine genes. It had been hypothesized that coexpressed gene clusters might correspond to large chromatin domains. In contradiction, we find that most of these clusters contain only 2 genes whose coexpression may be due to transcriptional read-through or the activity of bidirectional promoters.
A phase I study to determine the safety, pharmacokinetics and pharmacodynamics of a dual VEGFR and FGFR inhibitor, brivanib, in patients with advanced or metastatic solid tumors
Authors: D.J. Jonker, L.S. Rosen, M.B. Sawyer, F. de Braud, G. Wilding, C.J. Sweeney, G.C. Jayson, G.A. McArthur, G. Rustin, G. Goss, J. Kantor, L. Velasquez, S. Syed, O. Mokliatchouk, D.M. Feltquate, G. Kollia, D.S.A. Nuyten, S. Galbraith
Journal: Annals of Oncology (2010)
Measures of Success and Health-Related Quality of Life in Lower-Extremity Vascular Surgery
Authors: Joe Feinglass, Mark Morasch, Walter J. McCarthy
Journal: Annual Review of Medicine (2000)

Lower-extremity vascular surgery is most often indicated for patients with critical leg ischemia but has increasingly been used for patients with disabling intermittent claudication. This article reviews indications, follow-up protocols, and procedure-related outcomes including perioperative and late mortality, complications, and long-term patency rates, which vary with patient risk factors, vascular disease severity, and hospital volume. Population-based studies have yet to establish whether rates of limb-preserving bypass surgery are related to overall amputation rates, partly because of the continued high rate of primary amputation. The functional benefits of vascular surgery have been traditionally assessed by treadmill protocols and batteries of physical tests. Claudication treatment is increasingly being measured by both generic and disease-specific functional and health-related quality-of-life questionnaires. Patient self-reported measures of physical functioning and walking ability are reviewed. Finally, conclusions are presented about trends in lower-extremity bypass surgery rates.
Twist Promotes Tumor Cell Growth through YB-1 Expression
Authors: Masaki Shiota, Hiroto Izumi, Takamitsu Onitsuka, Naoya Miyamoto, Eiji Kashiwagi, Akihiko Kidani, Akira Yokomizo, Seiji Naito, Kimitoshi Kohno
Journal: Cancer Research (2008)

Abstract YB-1 controls gene expression through both transcriptional and translational mechanisms and is involved in various biological activities such as brain development, chemoresistance, and tumor progression. We have previously shown that YB-1 is overexpressed in cisplatin-resistant cells and is involved in resistance against DNA-damaging agents. Structural analysis of the YB-1 promoter reveals that several E-boxes may participate in the regulation of YB-1 expression. Here, we show that the E-box–binding transcription factor Twist is overexpressed in cisplatin-resistant cells and that YB-1 is a target gene of Twist. Silencing of either Twist or YB-1 expression induces G1 phase cell cycle arrest of tumor cell growth. Significantly, reexpression of YB-1 led to increase colony formation when Twist expression was down-regulated by small interfering RNA. However, cotransfection of Twist expression plasmid could not increase colony formation when YB-1 expression was down-regulated. Collectively, these data suggest that YB-1 is a major downstream target of Twist. Both YB-1 and Twist expression could induce tumor progression, promoting cell growth and driving oncogenesis in various cancers. Thus, both YB-1 and Twist may represent promising molecular targets for cancer therapy. [Cancer Res 2008;68(1):98–105]
Cytosolic recognition of flagellin by mouse macrophages restricts <i>Legionella pneumophila</i> infection
Authors: Ari B. Molofsky, Brenda G. Byrne, Natalie N. Whitfield, Cressida A. Madigan, Etsu T. Fuse, Kazuhiro Tateda, Michele S. Swanson
Journal: The Journal of Experimental Medicine (2006)

To restrict infection by Legionella pneumophila, mouse macrophages require Naip5, a member of the nucleotide-binding oligomerization domain leucine-rich repeat family of pattern recognition receptors, which detect cytoplasmic microbial products. We report that mouse macrophages restricted L. pneumophila replication and initiated a proinflammatory program of cell death when flagellin contaminated their cytosol. Nuclear condensation, membrane permeability, and interleukin-1β secretion were triggered by type IV secretion-competent bacteria that encode flagellin. The macrophage response to L. pneumophila was independent of Toll-like receptor signaling but correlated with Naip5 function and required caspase 1 activity. The L. pneumophila type IV secretion system provided only pore-forming activity because listeriolysin O of Listeria monocytogenes could substitute for its contribution. Flagellin monomers appeared to trigger the macrophage response from perforated phagosomes: once heated to disassemble filaments, flagellin triggered cell death but native flagellar preparations did not. Flagellin made L. pneumophila vulnerable to innate immune mechanisms because Naip5+ macrophages restricted the growth of virulent microbes, but flagellin mutants replicated freely. Likewise, after intratracheal inoculation of Naip5+ mice, the yield of L. pneumophila in the lungs declined, whereas the burden of flagellin mutants increased. Accordingly, macrophages respond to cytosolic flagellin by a mechanism that requires Naip5 and caspase 1 to restrict bacterial replication and release proinflammatory cytokines that control L. pneumophila infection.
Hydrogen Peroxide Produced by Angiopoietin-1 Mediates Angiogenesis
Authors: Young Mee Kim, Kyung Eun Kim, Gou Young Koh, Ye-Shih Ho, Kong-Joo Lee
Journal: Cancer Research (2006)

Abstract Angiopoietin-1 (Ang1) mediates angiogenesis by enhancing endothelial cell survival and migration. It is also known that Ang1 activates Tie2, an endothelial-specific tyrosine kinase receptor, but the molecular mechanism of this process is not clear. In this study, we investigated whether reactive oxygen species (ROS) production plays a role in Ang1-mediated angiogenesis. We found that human umbilical vein endothelial cells treated with Ang1 produce ROS transiently, which was suppressed by NADPH oxidase inhibitor, diphenylene-iodonium chloride, and rotenone. The Ang1-induced ROS was identified as hydrogen peroxide (H2O2) using adenovirus-catalase infection. Removal of H2O2 by adenovirus-catalase significantly suppressed Ang1-induced in vitro endothelial cell migration, in vivo tubule formation and angiogenesis, and activation of p44/42 mitogen-activated protein kinase (MAPK), involved in cell migration, and delayed the deactivation of Akt phosphorylation involved in cell survival. Supporting to in vitro data, Ang1-induced vascular remodeling in catalase (−/−) mice was more prominent than in catalase (+/+) mice: Ang1-induced increases of the diameter of terminal arterioles and the postcapillary venules in catalase (−/−) mice were significant compared with catalase (+/+) mice. These results show that Ang1-induced H2O2 plays an important role in Ang1-mediated angiogenesis by modulating p44/42 MAPK activity. (Cancer Res 2006; 66(12): 6167-74)
Improved Prandial Glucose Control With Lower Risk of Hypoglycemia With Nateglinide Than With Glibenclamide in Patients With Maturity-Onset Diabetes of the Young Type 3
Authors: Tiinamaija Tuomi, Elina H. Honkanen, Bo Isomaa, Leena Sarelin, Leif C. Groop
Journal: Diabetes Care (2006)

OBJECTIVE—To study the effect of the short-acting insulin secretagogue nateglinide in patients with maturity-onset diabetes of the young type 3 (MODY3), which is characterized by a defective insulin response to glucose and hypersensitivity to sulfonylureas. RESEARCH DESIGN AND METHODS—We compared the acute effect of nateglinide, glibenclamide, and placebo on prandial plasma glucose and serum insulin, C-peptide, and glucagon excursions in 15 patients with MODY3. After an overnight fast, they received on three randomized occasions placebo, 1.25 mg glibenclamide, or 30 mg nateglinide before a standard 450-kcal test meal and light bicycle exercise for 30 min starting 140 min after the ingestion of the first test drug. RESULTS—Insulin peaked earlier after nateglinide than after glibenclamide or placebo (median [interquartile range] time 70 [50] vs. 110 [20] vs. 110 [30] min, P = 0.0002 and P = 0.0025, respectively). Consequently, compared with glibenclamide and placebo, the peak plasma glucose (P = 0.031 and P &amp;lt; 0.0001) and incremental glucose areas under curve during the first 140 min of the test (P = 0.041 and P &amp;lt; 0.0001) remained lower after nateglinide. The improved prandial glucose control with nateglinide was achieved with a lower peak insulin concentration than after glibenclamide (47.0 [26.0] vs. 80.4 [71.7] mU/l; P = 0.023). Exercise did not induce hypoglycemia after nateglinide or placebo, but after glibenclamide six patients experienced symptomatic hypoglycemia and three had to interrupt the test. CONCLUSIONS—A low dose of nateglinide prevents the acute postprandial rise in glucose more efficiently than glibenclamide and with less stimulation of peak insulin concentrations and less hypoglycemic symptoms.
An evaluation of a 2% erythromycin ointment in the topical therapy of acne vulgaris
Authors: Jack L. Lesher, Dan K. Chalker, J. Graham Smith, Lyn C. Guenther, Charles N. Ellis, John J. Voorhees, Alan R. Shalita, Harry C. Klauda
Journal: Journal of the American Academy of Dermatology (1985)