tbuckley/cabot-search huggingface dataset:
Long-term nasal intermittent positive pressure ventilation (NIPPV) in sixteen consecutive patients with bronchiectasis: a retrospective study
Authors: A Gacouin, B Desrues, H Lena, ML Quinquenel, J Dassonville, P Delaval
Journal: European Respiratory Journal (1996)

Life expectancy and quality of life are poor in patients with chronic respiratory failure due to bronchiectasis. The indication for nocturnal nasal intermittent positive pressure ventilation (NIPPV) remains controversial in chronic obstructive lung disease. The purpose of the present study was to determine whether some of the objectives of home mechanical ventilation, i.e. improvement in blood gas values and reduced length of hospitalization, were fulfilled by NIPPV and oxygen plus medical treatment in patients with chronic respiratory failure due to bronchiectasis. Sixteen consecutive patients (12 females and four males; mean age 57 +/- 11 yrs) with chronic respiratory failure due to bronchiectasis, treated at home with nocturnal NIPPV in addition to oxygen therapy, were retrospectively studied in terms of blood gas values and duration of hospitalization before and after NIPPV. Details of the therapy received by each patient were recorded. Nine patients agreed to complete a questionnaire to determine their perception of the benefits of the treatment. NIPPV was performed using a volumetric respirator and was applied with a customized nasal mask modelled with silicone paste. NIPPV was used for a mean of 26 months (range 0.5-60 months). Eleven patients were alive 12 months after use of NIPPV. No significant improvement in blood gas values was noted on room air during NIPPV, but arterial carbon dioxide tension (Pa,CO2) stabilized after the period of worsening observed before initiation of NIPPV. Duration of hospitalization, the year before and the year after NIPPV, was 19 (3-40) and 16 (8-37) days, respectively (NS). For the 11 patients who were alive 2 yrs after the start of NIPPV, duration of hospitalization the year before NIPPV and between 12 and 24 months after NIPPV were 17 (4-40) and 7 (2-27) days, respectively (p < 0.05). Nine patients who had received NIPPV for at least 12 months at the time of the study reported an improvement in their quality of life. The results suggest that home ventilatory support by nasal intermittent positive pressure ventilation offers an acceptable alternative to tracheotomy, with less discomfort, in the management of severe respiratory failure due to bronchiectasis, in order to allow the patient to return home. These results should be confirmed by controlled studies.
Pattern of Antioxidant and DNA Repair Gene Expression in Normal Airway Epithelium Associated with Lung Cancer Diagnosis
Authors: Thomas Blomquist, Erin L. Crawford, D'Anna Mullins, Youngsook Yoon, Dawn-Alita Hernandez, Sadik Khuder, Patricia L. Ruppel, Elizabeth Peters, David J. Oldfield, Brad Austermiller, John C. Anders, James C. Willey
Journal: Cancer Research (2009)

In previous studies, we reported that key antioxidant and DNA repair genes are regulated differently in normal bronchial epithelial cells of lung cancer cases compared with non-lung cancer controls. In an effort to develop a biomarker for lung cancer risk, we evaluated the transcript expressions of 14 antioxidant, DNA repair, and transcription factor genes in normal bronchial epithelial cells (HUGO names CAT, CEBPG, E2F1, ERCC4, ERCC5, GPX1, GPX3, GSTM3, GSTP1, GSTT1, GSTZ1, MGST1, SOD1, and XRCC1). A test comprising these 14 genes accurately identified the lung cancer cases in two case-control studies. The receiver operating characteristic-area under the curve was 0.82 (95% confidence intervals, 0.68-0.91) for the first case-control set (25 lung cancer cases and 24 controls), and 0.87 (95% confidence intervals, 0.73-0.96) for the second set (18 cases and 22 controls). For each gene included in the test, the key difference between cases and controls was altered distribution of transcript expression among cancer cases compared with controls, with more lung cancer cases expressing at both extremes among all genes (Kolmorogov-Smirnov test, D = 0.0795; P = 0.041). A novel statistical approach was used to identify the lower and upper boundaries of transcript expression that optimally classifies cases and controls for each gene. Based on the data presented here, there is an increased prevalence of lung cancer diagnosis among individuals that express a threshold number of key antioxidant, DNA repair, and transcription factor genes at either very high or very low levels in the normal airway epithelium.
Antiviral resistance during the 2009 influenza A H1N1 pandemic: public health, laboratory, and clinical perspectives
Authors: Aeron C Hurt, Tawee Chotpitayasunondh, Nancy J Cox, Rod Daniels, Alicia M Fry, Larisa V Gubareva, Frederick G Hayden, David S Hui, Olav Hungnes, Angie Lackenby, Wilina Lim, Adam Meijer, Charles Penn, Masato Tashiro, Timothy M Uyeki, Maria Zambon
Journal: The Lancet Infectious Diseases (2011)
Force-velocity characteristics and active tension in relation to content and orientation of smooth muscle cells in aortas from normotensive and spontaneous hypertensive rats.
Authors: A Arner, B Uvelius
Journal: Circulation Research (1982)

Segments of abdominal aorta from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats (20-25 weeks) were compared with respect to force production and dynamic mechanical properties. The preparations were mounted in vitro for determination of optimal length (lo) for active force, and then maximally stimulated (high-K+ solution, 10 mm Ca2+, 10(-5) m noradrenaline), and fixed for electron microscopy. Muscle cellular volume per mm vessel wall was significantly (p less than 0.01) higher in SHR (0.14 +/- 0.009 mm3, n = 7) compared to WKY (0.11 +/- 0.004 mm3, n = 7). Unchanged cell length and unaltered cross-sectional area (17 micrometers2) of nucleus containing cell profiles in SHR suggest an increased number of cells in the media. No difference was found in maximum force per unit cell area between SHR (271 +/- 31, n = 7) and WKY (305 +/- 49 mN/mm2, n = 7). Cell orientation was almost circular in both groups, showing that force was measured in parallel to the cell long axis. Aortic segments were mounted in an apparatus for quick-release experiments. They were maximally stimulated and force steps were imposed at peak of contractions. The series elastic component, characterized by the initial elastic recoils at 0.75 lo, has similar stiffness values in SHR and WKY. Velocities were measured 100 msec after release. The results were fitted to Hill's equation and maximum shortening velocity (Vmax) computed. No difference in Vmax was found at 0.75 lo (WKY: 0.048 +/- 0.005; SHR: 0.042 +/- 0.006 lo/s, n = 6 for both). At 0.85 lo, the data were corrected for passive tension (40% to total). Vmax at 0.85 lo was 0.071 +/- 0.009 lo/s (n = 5) for WKY, and 0.069 +/- 0.007 lo/s (n = 5) for SHR. Similar Vmax and force per cell cross-sectional area suggest similar characteristics of actomyosin interaction in SHR and WKY aorta.
Muscle Ergoreceptor Overactivity Reflects Deterioration in Clinical Status and Cardiorespiratory Reflex Control in Chronic Heart Failure
Authors: Piotr P. Ponikowski, Tuan P. Chua, Darrel P. Francis, Alessandro Capucci, Andrew J.S. Coats, Massimo F. Piepoli
Journal: Circulation (2001)

Background In chronic heart failure (CHF), overactivation of ergoreceptors (afferents sensitive to the metabolic effects of muscular work) may be a link between peripheral changes, sympathetic overactivation, and increased hemodynamic and ventilatory responses to exercise. The relationship between ergoreceptors, autonomic changes, and the progression of the syndrome has not yet been studied. Methods and Results Thirty-eight stable CHF patients (age, 57±1 years; ejection fraction, 26±2%) were compared with 12 age-matched normal control subjects. The ergoreflex contribution to the ventilatory and hemodynamic responses to exercise, together with peripheral and central chemoreceptor sensitivity, arterial baroreflex sensitivity, plasma norepinephrine, epinephrine, and heart rate variability, were measured. Enhanced ergoreflex effects on ventilation (78±2% versus 50±8%), peripheral chemosensitivity (0.6±0.4 versus 0.2±0.1 L/min per percent Sa o 2 ), and central chemosensitivity (2.9±0.2 versus 2.0±0.2 L · min −1 · mm Hg −1 ) and an impaired baroreflex function (4.1±0.6 versus 9.1±5.6 ms/mm Hg) were confirmed in CHF compared with control subjects ( P &lt;0.01 in all comparisons). Ergoreceptor overactivity was associated with a worse symptomatic state (NYHA class, P &lt;0.05), lower exercise tolerance (peak V o 2 , P &lt;0.05), and pronounced exercise hyperventilation (V̇ e /V co 2 , P &lt;0.01). It was also a strong predictor of increased central chemosensitivity (independently of clinical parameters), baroreflex impairment, and sympathetic activation (plasma catecholamines and heart rate variability indexes; all P &lt;0.05). In multivariate analysis, among all reflexes studied, the ventilatory component of the ergoreflex was the only independent predictor of peak V o 2 and V̇ e /V co 2 . Conclusions In CHF, overactivation of the ergoreflex is associated with abnormal cardiorespiratory reflex control, independently of clinical severity. Among impaired reflexes, overactivation of the ergoreflex is an important determinant of exercise hyperventilation and reduced exercise tolerance.
EGFR-AKT-Smad Signaling Promotes Formation of Glioma Stem-like Cells and Tumor Angiogenesis by ID3-Driven Cytokine Induction
Authors: Xun Jin, Jinlong Yin, Sung-Hak Kim, Young-Woo Sohn, Samuel Beck, Young Chang Lim, Do-Hyun Nam, Yun-Jaie Choi, Hyunggee Kim
Journal: Cancer Research (2011)

Abstract Aberrant activation of receptor tyrosine kinases (RTK) is causally linked to the pathobiological traits of glioblastoma and genesis of glioma stem-like cells (GSC), but the underlying mechanism is still unknown. Here, we show that epidermal growth factor receptor (EGFR) signaling regulates the proliferation, angiogenesis, and acquisition of GSC characteristics by inducing inhibitor of differentiation 3 (ID3) and ID3-regulated cytokines [GRO1 and interleukins (IL)-6 and 8] induction. We found that EGFR-mediated ID3 expression was regulated by Smad5, which was directly phosphorylated by AKT. Furthermore, ID3 alone imparted GSC features to primary astrocytes derived from Ink4a/Arf-deficient mouse, and EGFR–ID3–IL-6 signaling axis gave rise to tumor cell heterogeneity. Conversely, EGFR inhibitors suppressed EGFR-AKT-Smad5–driven induction of ID3, which led to a decrease in the tumorsphere forming ability of GSCs and U87MG cells that possess an active mutant EGFR, EGFRvIII, without obvious cytotoxic effects. However, these cells seemed to regain colonogenic ability after removal of the EGFR inhibitors. Together, the results delineate a novel integrative molecular mechanism in which the RTK-ID signaling pathway governs genesis and maintenance of GBM histopathologic features, such as GSCs-based tumor initiation, progression, and angiogenesis. Cancer Res; 71(22); 7125–34. ©2011 AACR.
Vascular Superoxide Production by NAD(P)H Oxidase
Authors: Tomasz J. Guzik, Nick E. J. West, Edward Black, Denise McDonald, Chandi Ratnatunga, Ravi Pillai, Keith M. Channon
Journal: Circulation Research (2000)

Abstract —Superoxide anion plays important roles in vascular disease states. Increased superoxide production contributes to reduced nitric oxide (NO) bioactivity and endothelial dysfunction in experimental models of vascular disease. We measured superoxide production by NAD(P)H oxidase in human blood vessels and examined the relationships between NAD(P)H oxidase activity, NO-mediated endothelial function, and clinical risk factors for atherosclerosis. Endothelium-dependent vasorelaxations and direct measurements of vascular superoxide production were determined in human saphenous veins obtained from 133 patients with coronary artery disease and identified risk factors. The predominant source of vascular superoxide production was an NAD(P)H-dependent oxidase. Increased vascular NAD(P)H oxidase activity was associated with reduced NO-mediated vasorelaxation. Furthermore, reduced endothelial vasorelaxations and increased vascular NAD(P)H oxidase activity were both associated with increased clinical risk factors for atherosclerosis. Diabetes and hypercholesterolemia were independently associated with increased NADH-dependent superoxide production. The association of increased vascular NAD(P)H oxidase activity with endothelial dysfunction and with clinical risk factors suggests an important role for NAD(P)H oxidase–mediated superoxide production in human atherosclerosis. The full text of this article is available at http://www.circresaha.org.
Antithrombin reduces shedding of the endothelial glycocalyx following ischaemia/reperfusion
Authors: D. Chappell, M. Jacob, K. Hofmann-Kiefer, M. Rehm, U. Welsch, P. Conzen, B. F. Becker
Journal: Cardiovascular Research (2009)

Antithrombin is an important inhibitor of the coagulation system, additionally exerting specific anti-inflammatory effects on endothelial cells. Healthy vascular endothelium is coated by the endothelial glycocalyx, diminution of which increases capillary permeability, e.g. after ischaemia. Antithrombin is known to infiltrate the glycocalyx, binding to glycosaminoglycans, and to preserve the glycocalyx after application tumour necrosis factor-alpha. We investigated the influence of antithrombin on glycocalyx subjected to ischaemia/reperfusion.Isolated guinea pig hearts were perfused with Krebs-Henseleit buffer (KHB). Antithrombin was applied to achieve physiological levels (1 U/mL) before inducing 20 min of ischaemia (37 degrees C). Hearts were reperfused for 20 min at constant flow (baseline perfusion pressure 70 cmH(2)O) with KHB or KHB plus 2 g% hydroxyethyl starch (130 kDa). Coronary net fluid filtration was assessed directly by measuring transudate formation on the epicardial surface. Post-ischaemic coronary release of syndecan-1 and heparan sulfate was quantified by ELISA. Hearts were perfusion-fixed to visualize the glycocalyx by electron microscopy. Ischaemia/reperfusion caused degradation of the glycocalyx, enhanced coronary perfusion pressure, and increased vascular permeability. Antithrombin significantly reduced post-ischaemic glycocalyx shedding, coronary perfusion pressure, coronary leak, and tissue oedema formation compared to untreated hearts. Additional application of colloid augmented these actions of antithrombin. Electron microscopy revealed a mostly intact glycocalyx after antithrombin treatment.Antithrombin preserves the endothelial glycocalyx, sustaining the vascular barrier function and reducing interstitial oedema. The potentiated effect of colloid in these hearts suggests that the prevention of shedding should be of functional benefit also in vivo.
Gene transfer into vascular cells using adeno-associated virus (AAV) vectors
Authors: Y Maeda
Journal: Cardiovascular Research (1997)

Objectives: Recombinant viral vectors based on the nonpathogenic parvovirus, adeno-associated virus (AAV), have a number of attractive features for gene therapy, including the ability to transduce non-dividing cells and its long-term transgene expression. In this study, an AAV vector containing bacterial β-galactosidase gene (lacZ) was used to transduce cultured rat vascular smooth muscle cells (VSMC) in vitro and rat thoracic aortas ex vivo. Methods: VSMC were transduced with AAV-lacZ at multiplicities of infection (MOI) ranging from 5.0×105 to 1.0×107. Expression of β-galactosidase (β-gal) in VSMC was evaluated by X-gal staining and a β-gal ELISA method. Excised rat aortas were incubated with medium containing AAV-lacZ. Expression of β-gal in the aortic segments was evaluated by X-gal staining. Results: With increasing MOI, up to 50% of cultured VSMC were positive by X-gal staining and the β-gal expression increased up to 15 ng/mg protein. The expression gradually decreased during the culture but was detectable for at least 1 month. In the ex vivo study, AAV vectors transduced endothelial and adventitial cells in rat aortic segments, while no expression was seen in medial VSMC. Conclusions: AAV vectors can efficiently transduce rat VSMC in vitro. AAV-mediated ex vivo gene transfer into the normal aorta resulted in efficient gene transfer into endothelial and adventitial cells but not into medial VSMC. These findings suggest that AAV-based vectors are promising for use in cardiovascular gene therapy.
Medical and Social Aspects of the Treatment of Rheumatoid Arthritis: With Special Reference to Factors Affecting Prognosis
Authors: J. J. R. Duthie, M. Thompson, M. M. Weir, W. B. Fletcher
Journal: Annals of the Rheumatic Diseases (1955)

Composition of the GroupThe group for study consisted of all patients suffering from rheumatoid arthritis admitted to the Rheumatic Unit, Northern General Hospital, Edinburgh, between
Low Exchangeability of Selenocysteine, the 21st Amino Acid, in Vertebrate Proteins
Authors: S. Castellano, A. M. Andres, E. Bosch, M. Bayes, R. Guigo, A. G. Clark
Journal: Molecular Biology and Evolution (2009)

Selenocysteine (Sec), the 21st amino acid, is incorporated into proteins through the recoding of a termination codon, an inefficient translational process mediated by a complex molecular machinery. Sec is a rare amino acid in extant proteins, chemically similar to cysteine (Cys), found in homologous position to Cys of nonselenoprotein families. Selenoproteins account for the dependence of vertebrates on environmental selenium (Se) and have an important role in several Se-deficiency diseases. Selenoproteins are poorly characterized enzymes and reports on the functional exchangeability of Sec with Cys are limited and controversial. Whether the unique role of Sec in some selenoenzymes illustrates the broader contribution of Se to protein function is unknown (Gromer S, Johansson L, Bauer H, Arscott LD, Rauch S, Ballou DP, Williams CH Jr, Schirmer RH, Arnér ES. 2003. Active sites of thioredoxin reductases: why selenoproteins? Proc Natl Acad Sci USA. 100:12618–12623). Here, we address this question from an evolutionary perspective by the simultaneous identification of the patterns of divergence in almost half a billion years of vertebrate evolution and diversity within the human lineage for the full complement of enzymatic Sec residues in these proteomes. We complete this analysis with data for the homologous Cys residues in the same genomes. Our results indicate concerted purifying selection across Sec and Cys sites in all selenoproteomes, consistent with a unique role of Sec in protein function, low exchangeability, and an unknown degree of functional divergence with Cys homologs. The distinct biochemical properties of Sec, rather than the geographical distribution of Se, global O2 levels or Sec metabolic cost, appear to play a major role in driving adaptive changes in vertebrate selenoproteomes. A better understanding of the selenoproteomes and neutral evolutionary patterns in other taxa will be necessary to fully assess the generality of this conclusion.
Randomized, Controlled Evaluation of Short- and Long-Term Benefits of Heart Failure Disease Management Within a Diverse Provider Network
Authors: Carey Kimmelstiel, Daniel Levine, Kathleen Perry, Ayan R. Patel, Ara Sadaniantz, Noreen Gorham, Margaret Cunnie, Lynne Duggan, Linda Cotter, Patricia Shea-Albright, Athena Poppas, Kenneth LaBresh, Daniel Forman, David Brill, William Rand, Douglas Gregory, James E. Udelson, Beverly Lorell, Varda Konstam, Kathleen Furlong, Marvin A. Konstam
Journal: Circulation (2004)

Several trials support the usefulness of disease management (DM) for improving clinical outcomes in heart failure (HF). Most of these studies are limited by small sample size; absence of concurrent, randomized controls; limited follow-up; restriction to urban academic centers; and low baseline use of effective medications.We performed a prospective, randomized assessment of the effectiveness of HF DM delivered for 90 days across a diverse provider network in a heterogeneous population of 200 patients with high baseline use of approved HF pharmacotherapy. During a 90-day follow-up, patients randomized to DM experienced fewer hospitalizations for HF [primary end point, 0.55+/-0.15 per patient-year alive versus 1.14+/-0.22 per patient-year alive in control subjects; relative risk (RR), 0.48, P=0.027]. Intervention patients experienced reductions in hospital days related to a primary diagnosis of HF (4.3+/-0.4 versus 7.8+/-0.6 days hospitalized per patient-year; RR, 0.54; P<0.001), cardiovascular hospitalizations (0.81+/-0.19 versus 1.43+/-0.24 per patient-year alive; RR, 0.57; P=0.043), and days in hospital per patient-year alive for cardiovascular cause (RR, 0.64; P<0.001). Intervention patients showed a trend toward reduced all-cause hospitalizations and total hospital days. On long-term (mean, 283 days) follow-up, there was substantial attrition of the 3-month gain in outcomes, with sustained significant reduction only in days in hospital for cardiac cause.In a population with high background use of standard HF therapy, a DM intervention, uniformly delivered across varied clinical sites, produced significant short-term improvement in HF-related clinical outcomes. Longer-term benefit likely requires more active chronic intervention, even among patients who appear clinically stable.
Adjuvant chemotherapy in elderly patients with breast cancer: a survey of the Breast International Group (BIG)
Authors: L. Biganzoli, A. Goldhirsch, C. Straehle, M. Castiglione-Gertsch, P. Therasse, M. Aapro, A. Minisini, M.J. Piccart
Journal: Annals of Oncology (2004)

To collect oncologists' experience and opinion on adjuvant chemotherapy in elderly breast cancer patients.A questionnaire was circulated among the members of the Breast International Group.A total of 277 oncologists from 28 countries participated in the survey. Seventy years is the age cut-off commonly used to define a patient as elderly. Biological age and the biological characteristics of the tumor are the most frequently used criteria to propose adjuvant chemotherapy to an elderly patient. Combination therapy with cyclophosphamide, methotrexate and fluorouracil on days 1 and 8 is the most frequently prescribed regimen. Great interest exists in oral chemotherapy.There is interest among those who responded to the survey to validate a comprehensive geriatric assessment for use as a predictive instrument of toxicity and/or activity of anticancer therapy and to evaluate the role of a treatment option that is potentially less toxic and possibly as effective as polychemotherapy.