tbuckley/cabot-search huggingface dataset:
Visfatin and endothelial angiogenesis: AUTHORS' RETROSPECTIVE
Authors: R. Adya, B. K. Tan, J. Chen, H. S. Randeva
Journal: Cardiovascular Research (2012)

This editorial refers to an article by R. Adya et al . [2][1] published in Cardiovascular Research in 2008 (see [Box 1][2]). It is accompanied by an editorial by J. Waltenberger and E. Pardali (doi:10.1093/cvr/cvs180) as part of this Spotlight on Landmark Papers in Cardiovascular Research .

We are members of the ‘Metabolic and Vascular Research Group’, Warwick Medical School, UK, interested in novel adipokines proposed to have a functional interplay with the cardiovascular system. Since the discovery of visfatin/pre-B cell colony-enhancing factor (PBEF)/NAMPT in 2004,1 researchers world-wide have contributed to our present understanding of this ever-elusive molecule. We had published previously on visfatin-mediated effects in human endothelial cells contributing to endothelial angiogenesis.2 In this short editorial, we aim to briefly recapitulate the historical perspectives and previous contributions in the field of visfatin research.

PBEF (also termed nicotinamide phosphoribosyl transferase, NAMPT, or visfatin) was discovered as a novel cytokine secreted by activated human lymphocytes that functions as a growth factor for early B cell maturation.1 Despite the absence of a signal peptide required for secretion, PBEF/visfatin has been demonstrated to circulate freely in detectable ranges in plasma and serum, functioning as a classical cytokine.3,4 Pro-inflammatory properties of visfatin have been widely documented in several in vitro and in vivo studies. Earlier investigations reported both the presence of visfatin (PBEF) and its effects in inducing IL-6 and IL-8 cytokine release from amnion-like epithelial (WISH) cells and foetal membrane explants.5,6 Later studies elucidated the role of visfatin in delaying neutrophil apoptosis in experimental inflammation/clinical sepsis7 and thrombin-induced …

 [1]: #ref-2
 [2]: #F3
microRNA-34a and microRNA 199a-5p in COPD and their control of HIF-1α expression in pulmonary vasucular endothelial cells
Authors: Shiro Mizuno, Jose Gomez-Arroyo, Aysar Alhussaini, Donatas Kraskauskas, Carlyne Cool, Herman Bogaard, Norbert Voelkel
Journal: European Respiratory Journal (2011)

Rationale:  MicroRNAs (miRNA) are small noncording RNAs that silence target gene expression post-transcriptionally, and their impact on gene expression has been reported in various diseases. In the lungs from COPD patients, increased expression of tumor suppressor p53 and decreased expression of HIF-1α have been reported. However, the regulatory roles of these miRNAs in COPD lungs have not been evaluated.   Objective:  To assess the expression of miRNAs known to be associated with p53 and HIF-1α expression in lung tissues from patients with COPD/emphysema.   Methods:  Lung tissue samples from 55 patients were included in this study. Total RNA and miRNA extracted from lung tissues were used for RT-PCR analysis focused on miR-20b, miR-34a, miR-107, miR-199a-5p and miR-210. HIF-1α and p53 protein expression, AKT phosphorylation was measured by Western blot analysis. Gene silencing of HIF-1α and transfection of miR34a and miR-199a-5p precursor RNAs were performed in cultured human pulmonary microvascular endothelial cells (HPMVEC).   Measurements and main results:  miR-34a and miR-199a-5p expression was increased and the phosphorylation of AKT was decreased in COPD lungs. Transfection of the miR34a precursor decreased the phosphorylation of AKT, and transfection of the miR-199a-5p precursor decreased HIF-1α and VEGF protein expression in HPMVEC.   Conclusions:  These data indicate that miR-34a and miR-199a-5p contribute to the pathogenesis of emphysema, via decreasing the expression of HIF-1α and increasing the expression of p53 in the lung and thereby affecting the HIF-1a/VEGF-dependent lung structure maintenance program.
Immediate post-operative bronchoalveolar neutrophilia is associated with FEV1 early after lung transplantation
Authors: Robin Vos, David Ruttens, Stijn Verleden, Elly Vandermeulen, Jana Somers, Dirk Van Raemdonck, Jonas Yserbyt, Lieven Dupont, Bart Vanaudenaerde, Geert Verleden
Journal: European Respiratory Journal (2013)

Background 

Small case series have demonstrated that both donor and immediate post-operative recipient bronchoalveolar lavage (BAL) cytokine levels following lung transplantation (LTx) are associated with primary graft dysfunction (PGD) and recipient survival. We investigated whether recipient BAL neutrophilia during the first 48 hours post-transplant is associated with FEV1 early after LTx.

Methods 

A total of 198 transplant recipients (SS n=190/HL n=8), transplanted between 2002 and 2012, in whom routine BAL was performed during the first 48 hours post-transplant ; were retrospectively assessed for BAL neutrophilia, which was correlated with FEV1 (%pred) at 1 and 3 months post-operatively.

Results 

BAL was performed 18.3(±10.6) hours after allograft implantation. In univariate analysis, BAL neutrophilia inversely correlated with FEV1 at 3 months after LTx (p=0.025, r²=0.027) and a similar trend was seen with FEV1 after 1 month (p= 0.067, r²=0.021). In multivariate regression analysis, adjusted for duration of donor ventilation, donor pO2 at prelevation, allograft ischemic time, ECMO-use and PGD-score in the first 72 hours, BAL neutrophilia was still statistically significantly associated with FEV1 at 3 months (p=0.031).

Conclusions 

Immediate post-operative BAL neutrophilia is associated with FEV1 early after LTx, which may allow for early intervention to further improve outcome.

![Figure][1]  [1]: pending:yes
The Autoimmunity-Associated Gene CLEC16A Modulates Thymic Epithelial Cell Autophagy and Alters T Cell Selection
Authors: Cornelia Schuster, Kay D. Gerold, Kilian Schober, Lilli Probst, Kevin Boerner, Mi-Jeong Kim, Anna Ruckdeschel, Thomas Serwold, Stephan Kissler
Journal: Immunity (2015)
Effect of Nasal Continuous Positive Airway Pressure on Neuropsychological Function in Sleep Apnea–Hypopnea Syndrome
Authors: KATHE G. HENKE, JAMES J. GRADY, SAMUEL T. KUNA
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

A placebo-controlled, partial cross-over, double-blind, randomized study was performed with 46 adults with sleep apnea-hypopnea syndrome (SAHS) to determine the effect of therapeutic and subtherapeutic (0–1 cm H2O) nasal continuous positive airway pressure (CPAP) treatment on polysomnographic and neuropsychological testing. The following neuropsychological tests were administered: Geriatric Depression Scale, Trail Making A and B, Digit Span Test Forward and Backward, Epworth Sleepiness Scale, SteerClear, Digit Symbol, Controlled Oral Word Association, and Complex Figure Recall. Compared with results without CPAP, subtherapeutic CPAP did not affect any measured polysomnographic parameter. Comparison of neuropsychological test results obtained between the initial periods of effective treatment (Group 1, 16.1 d; Group 2, 19.6 d; p = NS) in all subjects showed significant improvements in Digit Symbol, Digit Span Backward, and Complex Figure tests. However, there were no group differences in changes in test results during the period when one group was on effective CPAP and the other on ineffective CPAP (Group 1, 16.1 d; Group 2, 13.9 d; p = NS). The results indicate the feasibility and importance of using ineffective CPAP as a placebo treatment and the importance of including a placebo control in studies evaluating the effect of treatment on neuropsychological function in SAHS.
Intrapleural Urokinase versus Normal Saline in the Treatment of Complicated Parapneumonic Effusions and Empyema
Authors: DEMOSTHENES BOUROS, SOPHIA SCHIZA, NIKOLAOS TZANAKIS, GEORGE CHALKIADAKIS, JOHN DROSITIS, NIKOLAOS SIAFAKAS
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Intrapleural administration of fibrinolytic agents has been shown to be effective and safe in the treatment of loculated parapneumonic pleural effusions. However, controlled studies of the possible role of the activity of urokinase (UK) through the volume effect are lacking. We therefore investigated the hypothesis that UK is effective through the lysis of pleural adhesions and not through the volume effect. Thirty-one consecutive patients with multiloculated pleural effusions were randomly assigned to receive either intrapleural UK (15 patients) or normal saline (NS) (16 patients) for 3 d, in a double-blind manner. All patients had inadequate drainage through a chest tube ( < 70 ml/24 h). UK was given daily through the chest tube in a dose of 100.000 IU diluted in 100 ml of NS. Controls were given the same volume of NS intrapleurally. Response was assessed by clinical outcome, fluid drainage, chest radiography, pleural ultrasonography (US) and/or computed tomography (CT). Clinical and radiographic improvement was noted in all but two patients in the UK group but in only four in the control group. The net mean volume drained during the 3-d treatment period was significantly greater in the UK group (970 ± 75 ml versus 280 ± 55 ml, p < 0.001). Pleural fluid drainage was complete in 13 (86.5%) patients in the UK group (two patients were treated through video-assisted thoracoscopy) but in only four (25%) in the control group. Twelve patients in the control group were subsequently treated with UK and six of them had complete drainage; the remaining six patients had complete drainage after video-assisted thoracoscopy. Our results suggest that UK is effective in the treatment of loculated pleural effusions through the lysis of pleural adhesions and not through the volume effect.
Cellular Interactions &lt;italic&gt;In Vitro&lt;/italic&gt; With Cells Derived From Tumors Induced by Murine Sarcoma Virus (Harvey)&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: P. J. Simons, A. A. Tuffery, D. J. McCully, E. J. Aw
Journal: JNCI Journal of the National Cancer Institute (1971)

Murine sarcoma virus (Harvey) [MSV(H)] rapidly induces tumors at the site of inoculation when injected intramuscularly into mice. Cells from such a tumor were established in culture. The primary culture in plastic dishes contained small, densely staining cells associated with fibroblasts and macrophages. On serial passage, the macrophages disappeared, and the fibroblasts formed a monolayer covered by small, densely staining spindle cells. By the ninth passage, the fibroblasts did not form a monolayer, and the individual, isolated fibroblasts acted as centers of growth for the spindle cells, which formed large cellular aggregates. When the same cells were plated in collagen-coated dishes, the spindle cells did not aggregate in the characteristic pattern. As the cultures growing on collagen approached confluence, large, multinucleate strap cells appeared. Clones of the small, spindle cells were grown on collagen, and on confluence they fused into strap cells. Evidence shows that the spindle cells were probably primitive mesenchymal cells which eventually developed myogenic properties, and that the large, multinucleate strap cells were myotubes. The spindle cells and the myotubes actively synthesized MSV. The histogenesis of MSV (H)-induced mouse tumors is discussed in relation to these findings.
Combined radiotherapy and chemotherapy in stage T3 and T4 nasopharyngeal carcinoma in children.
Authors: M Gasparini, F Lombardi, L Rottoli, E Ballerini, F Morandi
Journal: Journal of Clinical Oncology (1988)

Twelve children younger than 16 years affected by undifferentiated nasopharyngeal carcinoma (NPC) with advanced primary tumor (T3, T4) were treated with chemotherapy consisting of Adriamycin (ADM [doxorubicin; Adria Laboratories, Columbus, OH]), vincristine (VCR), and cyclophosphamide (CYC), and radiotherapy. Preradiation chemotherapy produced partial responses in eight of ten evaluable patients. Eleven of 12 patients achieved a complete response following radiotherapy. The actuarial 3-year continuous relapse-free survival (CRFS) was 75%. This represents a significant improvement when compared with the 8% rate obtained in a previous series of patients treated with radiotherapy either with or without adjuvant CYC.
Cationic compounds with activity against multidrug-resistant bacteria: interest of a new compound compared with two older antiseptics, hexamidine and chlorhexidine
Authors: M. Grare, H. Massimba Dibama, S. Lafosse, A. Ribon, M. Mourer, J.-B. Regnouf-de-Vains, C. Finance, R.E. Duval
Journal: Clinical Microbiology and Infection (2009)
Repeated IL-4 stimulation impairs STAT1 signaling and confers CD4+ T cell resistance to IL-27-mediated suppression
Authors: Zhihong Chen, Shanze Wang, Chunxue Bai, Hua Huang
Journal: European Respiratory Journal (2013)

Background:  Th2 cells play critical roles in the pathogenesis of allergic asthma. Established Th2 cells have been shown to resist reprogramming toward Th1 cells. The inherent Th2 stability poses a significant barrier in treating allergic diseases. We sought to understand the mechanisms by which asthmatic CD4+ T cells develop resistance to IL-27-mediated inhibition.   Methods:  We isolated and cultured CD4+ T cells from healthy individuals and allergic asthmatics and tested whether IL-27 can inhibit IL-4 production. STAT1 phosphorylation was analyzed by Western blot and flow cytometry. SOCS mRNA expressions were measured by quantitative PCR. The small interfering RNA method was used to knockdown SOCS3 mRNA expression.   Main Results:  We demonstrate that CD4+ T cells from asthmatic patients resisted human IL-27-mediated suppression of IL-4 production. We observed that repeated exposures to Th2-inducing conditions rendered healthy human CD4+ T cells resistant to IL-27-mediated inhibition. Using an in vitro murine culture system, we further demonstrated that repeated or higher doses of IL-4, but not IL-2, stimulation upregulated SOCS3 mRNA expression and impaired IL-27-induced STAT1 phosphorylation. Py-STAT1 expression was impaired in Th2 memory cells circulating in blood isolated from asthmatics, but not from normal subjects. Knockdown of SOCS3 expression restored IL-27-mediated inhibition.   Conclusions:  Our findings demonstrate that differentiated Th2 cells can resist IL27-induced reprogramming toward Th1 ells by downregulating STAT1 phosphorylation and upregulation of SOCS3 and may explain why asthmatic CD4+ T cells are resistant to IL-27- mediated inhibition.
Drug Abuse and the Emergency Room Physician
Authors: DAVID J. GREENBLATT, RICHARD I. SHADER
Journal: American Journal of Psychiatry (1974)

Physicians staffing emergency treatment facilities seldom are required to make hasty judgments regarding pharmacotherapy of drug abuse. Unnecessary morbidity frequently results from the use of barbiturates and major tranquilizers in the emergency room. The need for sedatives and tranquilizers should be carefully assessed before they are administered. Drug-induced agitation or panic will often subside spontaneously or in response to reassurance, obviating the need for coadministration of sedatives.
Preoperative determinants of the length of hospital stay in patients undergoing surgery for pancreatic cancer
Authors: Roger Carter, Oliver Aileen, V.V. Chandrabaln, John Kinsella
Journal: European Respiratory Journal (2011)

Introduction:  Surgery for pancreatic cancer is associated with considerable morbidity. Both surgeon-related and patient-related factors are important in determining postoperative outcome. Therefore most pancreatic surgery is now carried out in specialist centres. However, patient optimisation is complex since factors that determine postoperative morbidity are less well understood.   Objective:  To compare preoperative measures of patient comorbidity with length of hospital stay in patients undergoing pancreatic surgery.   Patients and methods:  103 patients who underwent surgery for pancreatic cancer (pancreatico-duodenectomy n=87,trial dissection with bypass n=16) had preoperative evaluation of body habitus, systemic inflammatory response (Glasgow Prognostic Score, mGPS) and routine blood analysis. Cardiopulmonary function (CPET) was measured in 54 patients. Length of hospital stay was recorded.   Results:  The median length of hospital stay was 17 days. 39 stayed ≤ 14 days and 64 >14 days. Length of hospital stay was not associated with body habitus or systemic inflammatory response. However, in patients with CPET, more patients with low anaerobic threshold (p=0.030),high base excess (0.056) and high VE/VCO2 (p=0.022) had a hospital stay >14 days. Prolonged hospital stay was associated with pancreatico-duodenectomy (p=0.027) and anastomotic failure (p   Conclusions:  CPET was the only pre-operative objective measure that correlated significantly with prolonged hospital stay. Length of stay is a useful surrogate marker of post-operative adverse events. Although CPET does not predict specific complications, it may determine the host response to major surgery and its immediate sequelae.
First-in-Man Clinical Use of Combined Near-Infrared Spectroscopy and Intravascular Ultrasound
Authors: Carl J. Schultz, Patrick W. Serruys, Martin van der Ent, Jurgen Ligthart, Frits Mastik, Scott Garg, James E. Muller, Mark A. Wilder, Anton F.W. van de Steen, Evelyn Regar
Journal: Journal of the American College of Cardiology (2010)
Abstract 18332: EphrinB2/EphB4 Signaling controls the Dose-Dependent Switch between Normal and Aberrant Angiogenesis by VEGF
Authors: Elena Groppa, Veronica Sacchi, Sime Brkic, Marianna Trani, Michael Heberer, Roberto Gianni-Barrera, Andrea Banfi
Journal: Circulation (2014)

Vascular Endothelial Growth Factor-A (VEGF) is the master regulator of vascular growth and it can induce either normal or aberrant angiogenesis depending on its dose in the microenvironment around each producing cell in vivo, and not on the total amount. However, stimulation of pericyte recruitment by co-expression of Platelet Derived Growth Factor-BB (PDGF-BB) could prevent aberrant structures despite heterogeneous and high VEGF levels and switch to homogeneously normal angiogenesis. Here we dissected the role of specific pericyte-mediated signaling pathways in the switch between normal and aberrant angiogenesis by VEGF. Monoclonal populations of transduced myoblasts were used to homogeneously express specific VEGF doses, inducing either normal or aberrant angiogenesis, and were further transduced to secrete soluble blockers of the TGFβ-1/TGFβ-R, Tie2/Angiopoietin or EphB4/EphrinB2 pathways (LAP, sTie2Fc and sEphB4, respectively). Two weeks after implantation into mouse limb muscles, neither TGFβ nor Angiopoietin blockade altered the normal angiogenesis by low VEGF, whereas EphrinB2/EphB4 inhibition caused a switch to aberrant angioma-like structures, similar to the effects of blocking pericyte recruitment. Conversely, gain-of-function of EphB4 signaling by systemic treatment with recombinant EphrinB2-Fc completely prevented aberrant angiogenesis by high VEGF levels and yielded normal networks of mature capillaries. We recently found that VEGF over-expression in muscle induces angiogenesis without sprouting, but by circumferential enlargement and longitudinal splitting (intussusception). EphB4 inhibition increased both endothelial proliferation and the diameter of initial enlargements induced by low VEGF (4 days), leading to a failure of splitting and progressive angioma growth. However, it did not interfere with pericyte recruitment, contrary to high VEGF alone. Conversely, EphB4 stimulation decreased both endothelial proliferation and the diameter of enlargements induced by high VEGF to values similar to low VEGF alone, and accelerated splitting into pericyte-covered capillary networks. In conclusion, EphrinB2/EphB4 signaling can prevent VEGF-induced aberrant angiogenesis by regulating intussusception.
How Gut handles your manuscript.
Authors: Robin Spiller
Journal: Gut (2005)

The editorial team in Gut are determined, on behalf of their readers, to attract the very best original research, the results of which will influence clinical practice in the immediate and medium term. With this in mind, we have embarked on a series of changes designed to encourage authors to consider Gut as the best vehicle for disseminating their original ideas.

Three years ago we converted to an all electronic submission process which has markedly speeded up the submission and review process. One unintended result has been to also increase the number of submissions substantially, meaning that the proportion of acceptances has fallen to around 1 in 6. Regrettably, many authors must be disappointed. However, on the plus side, this means we have some excellent manuscripts to consider.

Once manuscripts are uploaded, they are all seen by the Editor after submission on a daily basis and, providing they seem suitable, are allocated to the appropriate Associate Editor. After careful scrutiny, the Associate Editor selects and prioritises six reviewers and the first two are invited to review. Most reviewers are excellent, giving freely of their time, and return excellent reviews within the two week deadline. Of course, occasionally we have …
Suppurative mediastinitis after open-heart surgery: a comparison between cases caused by Gram-negative rods and by Gram-positive cocci
Authors: M.J. Rodríguez-Hernández, A. de Alarcón, J.M. Cisneros, I. Moreno-Maqueda, S. Marrero-Calvo, R. Leal, P. Camacho, R. Montes, J. Pachón
Journal: Clinical Microbiology and Infection (1997)
Slit2 modifies VEGF-induced angiogenic responses in rabbit skeletal muscle via reduced eNOS activity
Authors: Tiina Nieminen, Pyry I. Toivanen, Johanna P. Laakkonen, Tommi Heikura, Minna U. Kaikkonen, Kari J. Airenne, Seppo Ylä-Herttuala
Journal: Cardiovascular Research (2015)

AimsSlit2 is a possible modulator of VEGF-induced angiogenesis, but its effects have not been tested on large animal models. We studied the effect of Slit2 on therapeutic angiogenesis induced by VEGF receptor 2 (VEGFR2) ligands Vammin and VEGF-DΔNΔCin vivo in rabbit skeletal muscles. The Slit2 target genes were also studied by RNA sequencing in endothelial cells.
Predictive value of pro-inflammatory cytokine and pro-angiogenic factor in differentiating malignant from benign exudative effusion
Authors: Radwa Elhefny, Marwa Shaban, Olfat Shaker
Journal: European Respiratory Journal (2014)

The precise pathogenetic mechanisms of exudative effusions are still unsettled. Incremented permeability of the pleural microvasculature is attributed to factors that are released in inflammatory and malignant pleural diseases. Angiopoietin 2 (Ang-2) plays an essential role in angiogenesis and takes part in pleural inflammation. Interleukin-8(IL-8) influences proliferation and tumor angiogenesis. Objective: to investigate the relationship between inflammation, angiogenesis and etiologies of exudative effusions and its diagnostic value in differentiating malignant from benign effusion. Methods: the study includes 49 pleural fluid (PF) samples. PF and serum Ang-2, IL-8 levels were estimated. Results: ten patients had transudative and 39 patients had exudative effusions, subdivided into 16 benign and 23 malignant effusion. Both PF Ang-2 and IL-8 levels; and pleural fluid / serum ratio of Ang-2 and IL-8 were significantly higher in exudates than in transudates. PF Ang-2 and IL-8 levels were higher than serum Ang-2 level in both exudates and transudates. Both PF Ang-2 level and pleural fluid/serum ratio were significantly higher in benign than in malignant exudates while PF IL8-level was significantly higher in malignant than in benign exudates. Cut-off points for PF Ang-2 and PF IL8 in differentiating malignant from benign exudates were 15.67 ng/ml and 325.54 pg/ml respectively. Conclusion: our results support the evidence that both angiogenesis and inflammatory pathways are closely linked and that pleural inflammation and vascular permeability constitute the patho-genetic basis of the vast majority of exudative effusion.