tbuckley/cabot-search huggingface dataset:
Intestinal inflammation in postoperative ileus: pathogenesis and therapeutic targets
Authors: Jakub Rychter, Pere Clavé
Journal: Gut (2013)

Postoperative ileus (POI) is the most common gastrointestinal (GI) motility disorder managed by surgeons in their clinical practice. The definition, pathophysiology, prevention, diagnosis and management of POI are still not determined. An expert consensus defined POI as a ‘transient cessation of coordinated bowel motility after surgical intervention, which prevents effective transit of intestinal contents and/or tolerance of oral intake’.1 Primary POI is a physiological response that occurs in almost all patients following abdominal surgery and is usually spontaneously resolved by the 5th postoperative day after open laparotomy and by the 3rd day after laparoscopic surgery.1 The small intestine recovers its normal motility 8–24 h after surgery; the stomach, 24–48 h and the colon from 72 h, the left colon being the last to recover.2 As most surgeons wait for GI function recovery before allowing patients to be fed, POI has become the main cause of delayed hospital discharge after abdominal surgery. In addition, 19–25% of patients will develop prolonged primary ‘paralytic’ POI following major intestinal surgery.1 ,2 The clinical picture of primary POI ranges from oligosymptomatic patients to a full symptom cluster including abdominal pain, nausea and vomiting, abdominal distension and bloating, delayed passage of flatus and stool, and inability to progress to an oral diet. Diagnosis of POI relies on identification of these clinical features but diagnosis by abdominal auscultation for return of bowel sounds or passage …
Immunoblot and immunoelectronmicroscopic analysis of endemic Tunisian pemphigus
Authors: None JOLY, None MOKHTAR, None GILBERT, None THOMINE, None FAZZA, None BARDI, None LAURET, None AYED, None TRON, None KAMOUN
Journal: British Journal of Dermatology (1999)

Tunisian pemphigus is a newly described form of endemic pemphigus whose clinical, histological and epidemiological characteristics have recently been detailed. The objective of this study was to analyse the binding properties of autoantibodies present in sera from patients with endemic Tunisian pemphigus using immunoblotting and indirect immunoelectron microscopy (IEM). Thirty patients with pemphigus foliaceus (PF) and six with pemphigus vulgaris (PV) seen in the dermatology department of Tunis Hospital between 1992 and 1994 were selected for this study. Seven of 30 (23%) and six of 12 (50%) PF sera tested bound to the 160 kDa band of desmoglein 1 when tested on bovine tongue and human epidermal extracts, respectively. Two of six and two of three PV sera tested bound to the 130 kDa desmoglein 3 in these two extracts. Immunoblot and indirect IEM showed that 24 of 30 (80%) PF sera contained IgG1, IgG3 or IgG4 antibodies that bound to a 185‐kDa polypeptide localized on the desmosomal plaque. This immunological analysis showed that most endemic Tunisian pemphigus sera correspond to PF sera and are characterized by a high frequency of autoantibodies directed against a recently identified 185‐kDa antigen of the desmosomal plaque.
Cellular Targets of Gefitinib
Authors: Dirk Brehmer, Zoltán Greff, Klaus Godl, Stephanie Blencke, Alexander Kurtenbach, Martina Weber, Stefan Müller, Bert Klebl, Matt Cotten, György Kéri, Josef Wissing, Henrik Daub
Journal: Cancer Research (2005)

Abstract Targeted inhibition of protein kinases with small molecule drugs has evolved into a viable approach for anticancer therapy. However, the true selectivity of these therapeutic agents has remained unclear. Here, we used a proteomic method to profile the cellular targets of the clinical epidermal growth factor receptor kinase inhibitor gefitinib. Our data suggest alternative cellular modes of action for gefitinib and provide rationales for the development of related drugs.
Sumoylation Pathway Is Required to Maintain the Basal Breast Cancer Subtype
Authors: Maria V. Bogachek, Yizhen Chen, Mikhail V. Kulak, George W. Woodfield, Anthony R. Cyr, Jung M. Park, Philip M. Spanheimer, Yingyue Li, Tiandao Li, Ronald J. Weigel
Journal: Cancer Cell (2014)
Testable corollaries, a conceptual error, and neural correlates of Grush's synthesis
Authors: Thomas G. Campbell, John D. Pettigrew
Journal: Behavioral and Brain Sciences (2004)

As fundamental researchers in the neuroethology of efference copy, we were stimulated by Grush's bold and original synthesis. In the following critique, we draw attention to ways in which it might be tested in the future, we point out an avoidable conceptual error concerning emulation that Grush seems to share with other workers in the field, and we raise questions about the neural correlates of Grush's schemata that might be probed by neurophysiologists.
Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans
Authors: Iñaki Comas, Mireia Coscolla, Tao Luo, Sonia Borrell, Kathryn E Holt, Midori Kato-Maeda, Julian Parkhill, Bijaya Malla, Stefan Berg, Guy Thwaites, Dorothy Yeboah-Manu, Graham Bothamley, Jian Mei, Lanhai Wei, Stephen Bentley, Simon R Harris, Stefan Niemann, Roland Diel, Abraham Aseffa, Qian Gao, Douglas Young, Sebastien Gagneux
Journal: Nature Genetics (2013)
Stimulation of NADPH Oxidase by Oxidized Low-Density Lipoprotein Induces Proliferation of Human Vascular Endothelial Cells
Authors: ALEXANDRA HEINLOTH, KATHRIN HEERMEIER, ULRIKE RAFF, CHRISTOPH WANNER, JAN GALLE
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Oxidized low-density lipoprotein (OxLDL) exerts proliferation and apoptosis in vascular cells, depending on its concentration and the duration of exposure. Recent studies indicate that O 2 - is involved in cell cycle regulation and that OxLDL stimulates endothelial cells to produce O 2 - . This study examined the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as a potential source for O 2 - in the proliferation-inducing activity of OxLDL in cultured human umbilical vein endothelial cells (HUVEC). Human LDL was oxidized by Cu ++ , and proliferation of HUVEC was detected by 3H-thymidine incorporation. OxLDL (5 μg/ml) caused an increase in proliferation of HUVEC of 250 to 300%. OxLDL-induced proliferation was blocked by addition of the antioxidants superoxide dismutase and catalase, suggesting that enhanced O 2 - formation was involved. Diphenylene iodonium (DPI, 1 μM), an inhibitor of NADPH oxidase, also prevented OxLDL-induced proliferation of HUVEC, indicating that NADPH oxidase was the source for enhanced O 2 - formation. The OxLDL effect was mimicked by lysophosphatidylcholine (LPC, 10 μM), a compound formed during oxidation of LDL. LPC-induced proliferation was also prevented by coincubation with DPI. Treatment of HUVEC with O 2 - generated by the xanthine/xanthine oxidase reaction resulted in proliferation as did treatment with OxLDL. As expected, this stimulation could not be blocked by DPI. With the use of the cytochrome c-assay, it was demonstrated that OxLDL and LPC enhanced O 2 - formation in HUVEC (by factor 3.2 and by factor 3.5, respectively). Supporting the assumption that NADPH oxidase was the enzyme responsible for O 2 - formation, cells transfected with antisense oligonucleotides for NADPH oxidase showed a significantly reduced O 2 - formation after stimulation with OxLDL and LPC. OxLDL and its compound LPC induce proliferation of HUVEC through activation of NADPH oxidase. The active NADPH oxidase generates O 2 - , which mediates the proliferative effects.
Cloning and initial characterization of the human cardiac sodium channel (SCN5A) promoter
Authors: P Yang
Journal: Cardiovascular Research (2003)

Despite the primacy of the sodium current in cardiac electrophysiology and evidence that decreased sodium current is arrhythmogenic in humans, little is known about transcriptional regulation of the underlying gene, SCN5A.We have cloned a 2.7 kb segment of 5'-flanking region of SCN5A and identified multiple transcription initiation sites by primer extension and RNase protection. Transient transfection assays in neonatal mouse myocytes and in Chinese Hamster Ovary (CHO) cells were employed to identify promoter activities. PCR-single stranded conformational polymorphism (SSCP) analysis was used to screen DNA variants in the promoter region.The fragment includes >2 kb of upstream sequence, the 173-bp non-coding exon 1, and a portion of the 16-kb intron 1; the region is highly GC-rich and TATA-less. Transient transfection assays in neonatal mouse myocytes and in CHO cells identified (1) a core promoter in the -261/+140 segment, (2) regions conferring approximately 3-fold decreases from core promoter activity in the 5' upstream region (-261/-454 and -1020/-2109), and approximately 3-fold increases in intron 1 (+255/+410 and+539/+613), and (3) a very strong negative regulatory region between +613 and +754 in intron 1. A core promoter polymorphism, present in 6/142 (4%) of normal alleles screened, increased reporter activity approximately 50% in myocytes but not in CHO cells.The SCN5A promoter includes multiple positive and negative cis-acting elements extending into intron 1. A common polymorphism in this region modulates channel expression in vitro.
MOLECULAR EVENTS IN THE PATHOGENESIS OF HEPADNAVIRUS-ASSOCIATED HEPATOCELLULAR CARCINOMA
Authors: William S. Robinson, M.D
Journal: Annual Review of Medicine (1994)

▪ Abstract Chronic hepadnavirus infection is associated with hepatocellular carcinoma (HCC) in natural hosts such as humans, woodchucks, and Beechey ground squirrels. Several possible oncogenic mechanisms have been identified, including a potential role of the hepadnavirus x (hbx) gene, which transactivates transcription regulated by certain cis-acting sequences, e.g. regulatory sequences of the hepatitis B virus (HBV) and heterologous regulatory sequences of other viruses and cellular genes. The oncogenic potential of hbx is suggested by the observation of HCCs in hbx transgenic mice, the oncogenic transformation of cells expressing hbx in culture, and the transactivation of oncogenes c-myc and c-jun by hbx. Cis-activation of cellular oncogenes N-myc and c-myc by viral promoter insertion has been a common finding in woodchuck hepatitis virus (WHV)-associated HCCs of woodchucks. No such cis-activation of any cellular gene has been shown in virus-associated HCCs of ground squirrels or humans. Amplification and overexpression of the c-myc gene has been a common finding in HCCs of ground squirrels, and is rare in woodchuck or human HCCs. Point mutations in the p53 gene and allelic deletion of p53 have been common findings in human HCCs, but have not been found in HCCs in woodchucks and have been found rarely in ground squirrels. How each of these genetic changes in the different hosts contributes to HCC remains to be determined, but apparently different changes in different HCCs of hepadnavirus-infected hosts suggest that several separate genetic events may contribute to the development of HCC. These events may differ in each host, and some may not result from a direct virus-specific mechanism. Chronic hepadnavirus infection is often associated with chronic necroinflammatory liver disease and cirrhosis, a pathologic process common to several other risk factors for HCC. This suggests that this pathologic process (necroinflammatory disease) may be hepatocarcinogenic regardless of the inciting agent. Thus hepadnavirus infection may play an important role in the development of HCC by causing chronic hepatitis and HCC with the same mechanisms by which other risk factors for HCC cause chronic necroinflammatory liver disease and HCC.
Chronic Alcoholism Alters Systemic and Pulmonary Glutathione Redox Status
Authors: Mary Y. Yeh, Ellen L. Burnham, Marc Moss, Lou Ann S. Brown
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Previous studies have linked the development and severity of acute respiratory distress syndrome with a history of alcohol abuse. In clinical studies, this association has been centered on depletion of pulmonary glutathione and subsequent chronic oxidant stress.Objectives: The impact on redox potential of the plasma or pulmonary pools, however, has never been reported.Methods: Plasma and bronchoalveolar lavage fluid were collected from otherwise healthy alcohol-dependent subjects and control subjects matched by age, sex, and smoking history.Measurements and Main Results: Redox potential was calculated from measured reduced and oxidized glutathione in plasma and lavage. Among subjects who did and did not smoke, lavage fluid glutathione redox potential was more oxidized in alcohol abusers by approximately 40 mV, which was not altered by dilution. This oxidation of the airway lining fluid associated with chronic alcohol abuse was independent of smoking history. A shift by 20 mV in plasma glutathione redox potential, however, was noted only in subjects who both abused alcohol and smoked.Conclusions: Chronic alcoholism was associated with alveolar oxidation and, with smoking, systemic oxidation. However, systemic oxidation did not accurately reflect the dramatic alcohol-induced oxidant stress in the alveolar space. Although there was compensation for the oxidant stress caused by smoking in control groups, the capacity to maintain a reduced environment in the alveolar space was overwhelmed in those who abused alcohol. The significant alcohol-induced chronic oxidant stress in the alveolar space and the subsequent ramifications may be an important modulator of the increased incidence and severity of acute respiratory distress syndrome in this vulnerable population.
Magnetically controlled growing rods for severe spinal curvature in young children: a prospective case series
Authors: Kenneth Man-Chee Cheung, Jason Pui-Yin Cheung, Dino Samartzis, Kin-Cheung Mak, Yat-Wa Wong, Wai-Yuen Cheung, Behrooz A Akbarnia, Keith Dip-Kei Luk
Journal: The Lancet (2012)
Effect of formoterol alone and in combination with aclidinium on electrocardiograms in dogs
Authors: Amadeu Gavaldà, Marisa Vinyals, Jordi Aubets, Jordi Gras
Journal: European Respiratory Journal (2012)

Introduction:  Co-administration of a long-acting β-agonist with an anticholinergic is common clinical practice for the management of COPD, but there are concerns that systemic exposure to both drugs could cause undesirable pharmacodynamic effects on the heart.   Aims:  To evaluate the cardiovascular safety of formoterol alone and in combination with aclidinium in conscious dogs.   Methods:  Formoterol (1, 3, 10 μg/kg iv), aclidinium (50, 167 μg/kg iv) and formoterol+aclidinium (1+17, 3+50, 10+167 mg/kg iv) were administered to fasting, male Beagle dogs (n=4; 13–16 kg) in a 3-min perfusion. Each dog received each dose with >6-day washout. Electrocardiograms were recorded at baseline (for 1 h) and 24 h post-administration (for 90 min) and assessed for ventricular tachycardia (VT) and premature ventricular complexes (PVC).   Results:  Formoterol alone showed a dose-dependent trend to induce VT. VT was observed in 0, 1 and 4 animals treated with formoterol 1, 3 and 10 μg/kg, respectively. Aclidinium alone (both doses) did not induce VT. The combination of formoterol+aclidinium resulted in VT in a similar number of animals as formoterol alone (2 and 3 animals with 3+50 and 10+167 μg/kg, respectively). Similar results were observed for PVC. At the highest doses of formoterol and aclidinium, the plasma concentrations corresponded to 32 and 4000 times those reported in human plasma after clinically relevant doses.   Conclusions:  Addition of aclidinium does not alter the incidence or rate of formoterol-induced VT or PVC in dogs. These results suggest that aclidinium has no synergistic interaction on cardiac function with β-agonists.  This study was supported by Almirall S.A., Barcelona, Spain.
Does <i>MYCN</i> Amplification Manifested as Homogeneously Staining Regions at Diagnosis Predict a Worse Outcome in Children with Neuroblastoma? A Children's Oncology Group Study
Authors: Lisa A. Moreau, Patrick McGrady, Wendy B. London, Hiroyuki Shimada, Susan L. Cohn, John M. Maris, Lisa Diller, A. Thomas Look, Rani E. George
Journal: Clinical Cancer Research (2006)

Abstract Purpose: MYCN amplification in neuroblastoma tumor cells is manifested primarily as double minutes (dmins), whereas in cell lines it often appears in the form of homogeneously staining regions (HSR), suggesting that HSRs are associated with a more aggressive tumor phenotype and worse clinical outcome. The aim of this study was to determine whether children with neuroblastoma in which MYCN oncogene amplification is manifested as HSRs at diagnosis have a worse prognosis than those whose tumors exhibit dmins. Experimental Design: A retrospective analysis of primary neuroblastomas analyzed for MYCN amplification by the Children's Oncology Group between 1993 and 2004 was done. Tumors with MYCN amplification were defined as having dmins, HSRs, or both (dmins + HSRs), and associations with currently used risk group stratification variables and patient outcome were assessed. Results: Of the 4,102 tumor samples analyzed, 800 (19.5%) had MYCN amplification. Among the 677 tumors for which the pattern of amplification was known, 629 (92.9%) had dmins, 40 (5.9%) had HSRs, and 8 (0.1%) had dmins + HSRs. Although MYCN amplification is associated with older age, higher stage, and unfavorable histology, whether the amplification occurred as dmins or HSRs did not significantly affect these risk factors. There were no differences in the event-free survival (EFS) or overall survival in patients with MYCN amplification manifested as either dmins or HSRs (5-year EFS, 35 ± 3% versus 38 ± 15%; P = 0.59). Although the eight patients with dmins + HSRs fared worse than either of the individual subgroups (EFS, 18 ± 16% versus 35 ± 3% for dmins and 38 ± 15% for HSRs), these differences were not significant. Conclusions: MYCN amplification in any form (HSRs or dmins) is associated with a poor outcome.
Journals' peer review system sometimes overlooks important research
Authors: A. O'Dowd
Journal: BMJ (2014)

The system used by leading scientific and clinical journals to judge whether to publish new research sometimes passes over important new studies that later have a big impact, a new paper has found.

The paper, published on 22 December,1 found that the peer review system used to judge whether new studies are worthy of publication enhances research overall but has limits. Under the system of peer review, decisions made by gatekeepers (editors and peer reviewers) can legitimise scientific findings and influence future research. However, currently there is a lack of appropriate, easily available data to gauge the quality of gatekeeper decision making in science, the paper said. In addition, scholars have expressed concern that there is a tendency to protect the scientific status quo, to suppress innovative findings, and for mistakes to be made, meaning that seminal scientific innovations are rejected by …
Trial of Everolimus-Eluting Stents or Bypass Surgery for Coronary Disease
Authors: Seung-Jung Park, Jung-Min Ahn, Young-Hak Kim, Duk-Woo Park, Sung-Cheol Yun, Jong-Young Lee, Soo-Jin Kang, Seung-Whan Lee, Cheol Whan Lee, Seong-Wook Park, Suk Jung Choo, Cheol Hyun Chung, Jae Won Lee, David J. Cohen, Alan C. Yeung, Seung Ho Hur, Ki Bae Seung, Tae Hoon Ahn, Hyuck Moon Kwon, Do-Sun Lim, Seung-Woon Rha, Myung-Ho Jeong, Bong-Ki Lee, Damras Tresukosol, Guo Sheng Fu, Tiong Kiam Ong
Journal: New England Journal of Medicine (2015)

Most trials comparing percutaneous coronary intervention (PCI) with coronary-artery bypass grafting (CABG) have not made use of second-generation drug-eluting stents.We conducted a randomized noninferiority trial at 27 centers in East Asia. We planned to randomly assign 1776 patients with multivessel coronary artery disease to PCI with everolimus-eluting stents or to CABG. The primary end point was a composite of death, myocardial infarction, or target-vessel revascularization at 2 years after randomization. Event rates during longer-term follow-up were also compared between groups.After the enrollment of 880 patients (438 patients randomly assigned to the PCI group and 442 randomly assigned to the CABG group), the study was terminated early owing to slow enrollment. At 2 years, the primary end point had occurred in 11.0% of the patients in the PCI group and in 7.9% of those in the CABG group (absolute risk difference, 3.1 percentage points; 95% confidence interval [CI], -0.8 to 6.9; P=0.32 for noninferiority). At longer-term follow-up (median, 4.6 years), the primary end point had occurred in 15.3% of the patients in the PCI group and in 10.6% of those in the CABG group (hazard ratio, 1.47; 95% CI, 1.01 to 2.13; P=0.04). No significant differences were seen between the two groups in the occurrence of a composite safety end point of death, myocardial infarction, or stroke. However, the rates of any repeat revascularization and spontaneous myocardial infarction were significantly higher after PCI than after CABG.Among patients with multivessel coronary artery disease, the rate of major adverse cardiovascular events was higher among those who had undergone PCI with the use of everolimus-eluting stents than among those who had undergone CABG. (Funded by CardioVascular Research Foundation and others; BEST ClinicalTrials.gov number, NCT00997828.).
Torsion of Vermiform Appendix
Authors: Ok Hee Won
Journal: JAMA (1977)

<h3>To the Editor.—</h3> Torsion of the appendix is a very uncommon cause of acute abdominal symptoms. Because of the rarity of this condition, the following case is described. <h3>Report of a Case.—</h3> A 35-year-old man was hospitalized with severe, continuous abdominal pain of five days' duration. It intensified nine hours before admission, localized in the right lower quadrant, and was accompanied by vomiting. There was no notable past medical history; specifically, the patient denied constipation and use of laxatives or enema. On admission, his pulse was 84 beats per minute; temperature, 37.3°C; blood pressure, 110/76 mm Hg; and respirations, 18/min. There was marked tenderness with rebound in the right lower quadrant of the abdomen. The bowel sounds appeared decreased. Rectal examination was unrevealing. Results of the remainder of the physical examination were unremarkable. Pertinent laboratory data included a WBC count of 10,700/cu mm, with 86% polymorphonuclear leukocytes. Chest and plain
Vitamin D Receptor and p21/WAF1 Are Targets of Genistein and 1,25-Dihydroxyvitamin D3 in Human Prostate Cancer Cells
Authors: Anuradha Rao, April Coan, Jo-Ellen Welsh, Wendy W. Barclay, Constantinos Koumenis, Scott D. Cramer
Journal: Cancer Research (2004)

We investigated mechanisms by which genistein and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] act synergistically to inhibit the growth of the human prostate cancer cell line LNCaP. We demonstrate that 1,25(OH)(2)D(3) and genistein cooperate to up-regulate the vitamin D receptor protein by increasing the stability of the vitamin D receptor. Genistein and 1,25(OH)(2)D(3) also cooperate to up-regulate the levels of p21/WAF1 (p21). Small interfering RNA-mediated knockdown of p21 expression showed that p21 is essential for significant growth inhibition of LNCaP cells in response to either compound or their combination. We conclude that one mechanism of synergism between genistein and 1,25(OH)(2)D(3) is through genistein modulation of vitamin D signaling.