tbuckley/cabot-search huggingface dataset:
Catecholamines can induce adenosine receptor-mediated protection of the myocardium but do not participate in ischemic preconditioning in the rabbit.
Authors: J D Thornton, J F Daly, M V Cohen, X M Yang, J M Downey
Journal: Circulation Research (1993)

The role of catecholamines in ischemic preconditioning is unclear. Accordingly, the effects of tyramine-induced norepinephrine release and alpha 1-receptor blockade were examined. Ischemic preconditioning with a 5-minute coronary occlusion 10 minutes before a 30-minute ischemic interval resulted in only 7.7 +/- 3.1% infarction of the risk area, significantly less than that in control rabbits with isolated 30-minute coronary occlusions (34.4 +/- 3.2%, P &lt; .01). Intravenous infusion of tyramine 10 minutes before 30 minutes of ischemia also protected the heart from infarction to an extent similar to that seen with ischemic preconditioning (6.9 +/- 2.4% infarction). This protection observed with tyramine infusion was eliminated by alpha 1-receptor blockade with BE 2254 (36.8 +/- 2.6% infarction) but was unaffected by beta-blockade with propranolol (10.5 +/- 2.4% infarction). Furthermore, the protection was unaffected when the tyramine-induced hypertension was attenuated by allowing blood to flow into a volume reservoir (3.9 +/- 0.8% infarction, P &lt; .01 vs control value). The nonselective adenosine-receptor blocker PD 115,199 also eliminated tyramine-induced protection (40.2 +/- 5.6% infarction), indicating that adenosine is involved in adrenergic-mediated protection. BE 2254 could not block ischemic preconditioning (3.9 +/- 1.1% infarction, P &lt; .01 vs control value). Therefore, catecholamine release before prolonged ischemia can protect the heart from infarction via the alpha 1-receptor, but adenosine receptor stimulation is also involved. alpha-Adrenergic stimulation does not appear to be critical to the protection observed after ischemic preconditioning.
Inhibition of collagen gene expression in systemic sclerosis dermal fibroblasts by mithramycin
Authors: N Sandorfi
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> The anti-tumour antibiotic mithramycin is also a potent inhibitor of fibrosis after glaucoma surgery. This drug displays high affinity binding to GC-rich sequences in DNA, including those present in the promoter of the gene encoding the α1 chain of type I collagen (COL1A1). <b>Objective:</b> To evaluate the effects of mithramycin on COL1A1 expression in systemic sclerosis fibroblasts. <b>Methods:</b> Confluent cultures of dermal fibroblasts from patients with recent onset diffuse systemic sclerosis were treated with mithramycin in vitro. Cell viability and protein expression were examined by fluorescence and confocal imaging. Type I collagen production was analysed by confocal imaging and metabolic labelling. COL1A1 messenger RNA levels and stability were assessed by northern hybridisation, and COL1A1 transcription was examined by transient transfections. <b>Results:</b> Treatment of systemic sclerosis fibroblasts with mithramycin (10–100 nmol/l) did not cause significant cytotoxicity. Type I collagen biosynthesis decreased by 33–40% and 50–70% in cells cultured with mithramycin at 10 nmol/l and 100 nmol/l, respectively. Mithramycin at 50 nmol/l decreased COL1A1 mRNA levels by 40–60%. The effects of mithramycin on collagen gene expression were mediated by transcriptional and post-transcriptional mechanisms as shown by the reduction of COL1A1 promoter activity and by a decrease in the stability of these transcripts, respectively. <b>Conclusions:</b> Mithramycin causes potent inhibition of collagen production and gene expression in systemic sclerosis dermal fibroblasts in vitro in the absence of cytotoxic effects. These results suggest that this drug may be an effective treatment for the fibrotic process which is the hallmark of systemic sclerosis.
Preservation of distal coronary perfusion during prolonged balloon inflation with an autoperfusion angioplasty catheter.
Authors: Z G Turi, C A Campbell, M V Gottimukkala, R A Kloner
Journal: Circulation (1987)

A newly designed balloon coronary angioplasty catheter that allows passive antegrade blood flow during balloon inflation (autoperfusion catheter) was compared with a standard balloon coronary angioplasty catheter. In a randomized sequence, inflations were performed for 3 min in the left circumflex coronary artery of 12 dogs with the standard catheter followed by the autoperfusion catheter or vice versa. During inflation with the standard catheter, the ST segment of standard limb lead II increased from -0.02 +/- 0.03 mV to 0.39 +/- 0.08 mV (p less than .001), whereas during inflation with the autoperfusion catheter the ST segment did not change (-0.03 +/- 0.03 vs -0.01 +/- 0.04 mV; p = NS). Regional myocardial blood flow measured by the radioactive microsphere technique in the posterior subepicardium and subendocardium was 0.12 +/- 0.03 and 0.08 +/- 0.03 ml/min/g, respectively, with the standard catheter as compared with 0.57 +/- 0.08 and 0.61 +/- 0.14 ml/min/g with the autoperfusion catheter (both p less than .01 compared with the standard catheter). Thus, unlike the standard catheter, the autoperfusion catheter allows for inflations up to 3 min in duration without producing deleterious changes in the ST segment or severe reductions in regional myocardial blood flow.
Biological Activity of Recombinant Tropomyosins from Ascaris lumbricoides and Cockroach among Patients with Asthma and/or Rhinitis from Brazil
Authors: A.C.A.F. Sousa, A.B.R. Santos, M.C.R. Barbosa, M.D. Chapman, L.K. Arruda
Journal: Journal of Allergy and Clinical Immunology (2010)
Serial measurements of soluble interleukin 2 receptor levels (sIL2-R) in children with juvenile rheumatoid arthritis treated with oral methotrexate.
Authors: C.D. Rose, P.T. Fawcett, K Gibney, R.A. Doughty, B.H. Singsen
Journal: Annals of the Rheumatic Diseases (1994)

To investigate the potential clinical utility of serial levels of sIL2-R as a marker of disease activity among children with juvenile rheumatoid arthritis (JRA) treated with methotrexate (MTX). sIL2-R levels, measured by ELISA, were evaluated in 16 JRA patients (10 polyarticular, six systemic-onset) treated with oral, weekly MTX. sIL2-R values were compared with those of 49 normal controls. Medical record review was used to obtain relevant clinical data. Joint counts (number of swollen joints) were used as indicators of clinical change. A reduction of 50% in joint counts between pre and post treatment measurements was considered a clinically significant response. The mean (SEM) sIL2-R value of pre treatment JRA of 1728(290) U/ml was significantly higher than the post treatment value of 921(229) U/ml (Wilcoxon Rank test, p < or = 0.001). Pre treatment values were also significantly different from the mean(SEM) of healthy controls of 519(19) U/ml (p < 0.001). Pre treatment sIL2-R levels of 2417(291) U/ml in systemic-onset JRA were significantly higher than sIL2-R values in polyarticular JRA patients of 1218(884) U/ml (Mann-Whitney rank test p < 0.001). Among the 13/16 children with good therapeutic responses (> or = 50% improved), the range of sIL2-R decreases was 154-2641 U/ml (mean 842 U/ml); sIL2-R levels increased in the three children with poor clinical responses to methotrexate. sIL2-R levels paralleled the course of disease in all patients. sIL2-R levels may be useful for monitoring therapeutic responses in children with JRA.
Hydralazine-Induced Tumor Hypoxia: A Potential Target for Cancer Chemotherapy
Authors: D. J. Chaplin
Journal: JNCI Journal of the National Cancer Institute (1989)

Currently available cancer chemotherapeutic agents have been designed to exploit subtle differences in proliferation and biochemistry that are known to exist between host and malignant cells. However, chemotherapeutic agents may also be used to exploit physiological differences between cancer and normal tissue. The present study was conducted to determine whether the reduction in blood flow to the tumor (and thus oxygen delivery) induced by the vasodilator hydralazine would increase the cytotoxicity of drugs known to be more toxic in regions of reduced oxygenation. Results obtained with three murine tumor models clearly demonstrate that hydralazine potentiates the tumor cytotoxicity of such agents to a greater extent than it does their systemic toxicity. This study indicates a potential strategy for increasing the efficacy of certain cancer chemotherapeutic agents in solid tumors.
Relationship Between Cardiovascular Risk as Predicted by Established Risk Scores Versus Plaque Progression as Measured by Serial Intravascular Ultrasound in Left Main Coronary Arteries
Authors: Clemens von Birgelen, Marc Hartmann, Gary S. Mintz, K. Gert van Houwelingen, Nadine Deppermann, Axel Schmermund, Dirk Böse, Holger Eggebrecht, Till Neumann, Mario Gössl, Heinrich Wieneke, Raimund Erbel
Journal: Circulation (2004)

Intravascular ultrasound (IVUS) is increasingly used as an end point in studies aimed at reducing progression or inducing regression of coronary artery disease. However, data linking serial changes by IVUS with clinical outcomes are scarce.In the absence of a validated risk score for secondary prevention, we compared 3 established risk scores for primary prevention--PROCAM, SCORE, and Framingham--with plaque progression and lumen reduction as assessed with serial IVUS (follow-up, 18+/-9 months) in atherosclerotic left main coronary arteries of 56 patients with established atherosclerosis. For all 3 algorithms, patients at highest estimated risk of events showed greater plaque progression than patients at lowest risk (P<0.05 to <0.01). There were positive linear relationships between the risk of clinical events and plaque progression (r=0.41 to 0.60; P<0.002 to <0.0001). This translated into a greater decrease in lumen dimensions with increasing risk (P<0.05, PROCAM and SCORE). Risk prediction using the PROCAM algorithm showed the strongest relation with serial IVUS. During follow-up, 18 patients suffered from adverse cardiovascular events; these patients had an annual plaque progression that was significantly greater than other patients (25.2+/-19.4% versus 5.9+/-15.6%, P<0.001).There was a positive linear relationship between the estimated risk of clinical events derived from all 3 established risk-score algorithms and the extent of plaque progression measured by serial IVUS. This translated into stenosis progression (reduction in lumen dimensions) with increasing clinical risk.
Non-coding RNAs: a key to future personalized molecular therapy?
Authors: Marco Galasso, Maria Elena Sana, Stefano Volinia
Journal: Genome Medicine (2010)

Continual discoveries on non-coding RNA (ncRNA) have changed the landscape of human genetics and molecular biology. Over the past ten years it has become clear that ncRNAs are involved in many physiological cellular processes and contribute to molecular alterations in pathological conditions. Several classes of ncRNAs, such as small interfering RNAs, microRNAs, PIWI-associated RNAs, small nucleolar RNAs and transcribed ultra-conserved regions, are implicated in cancer, heart diseases, immune disorders, and neurodegenerative and metabolic diseases. ncRNAs have a fundamental role in gene regulation and, given their molecular nature, they are thus both emerging therapeutic targets and innovative intervention tools. Next-generation sequencing technologies (for example SOLiD or Genome Analyzer) are having a substantial role in the high-throughput detection of ncRNAs. Tools for non-invasive diagnostics now include monitoring body fluid concentrations of ncRNAs, and new clinical opportunities include silencing and inhibition of ncRNAs or their replacement and re-activation. Here we review recent progress on our understanding of the biological functions of human ncRNAs and their clinical potential.
ARRB1-Mediated Regulation of E2F Target Genes in Nicotine-Induced Growth of Lung Tumors
Authors: Piyali Dasgupta, Wasia Rizwani, Smitha Pillai, Rebecca Davis, Sarmistha Banerjee, Kevin Hug, Mark Lloyd, Domenico Coppola, Eric Haura, Srikumar P. Chellappan
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundNicotine induces the proliferation of non–small cell lung cancer (NSCLC) cells via nicotinic acetylcholine receptors and the arrestin, β1 (ARRB1) protein. However, whether ARRB1 translocates to the nucleus upon nicotinic acetylcholine receptor activation and how it regulates growth of human NSCLCs are not known.
Acute compartment syndrome of the anterior thigh following quadriceps strain in a footballer
Authors: B J Burns, J Sproule, H Smyth
Journal: British Journal of Sports Medicine (2004)

A rare case is presented of acute anterior compartment syndrome in the thigh of a footballer caused by an acute quadriceps strain, exacerbated by poor first aid and alcohol ingestion. Decompressive fasciotomy with subsequent split skin grafting of the wound defect resulted in a satisfactory outcome. The diagnosis requires a high index of suspicion lest it be overlooked with inevitably disastrous consequences.
The sequential use of endocrine treatment for advanced breast cancer: where are we?
Authors: C. Barrios, J.F. Forbes, W. Jonat, P. Conte, W. Gradishar, A. Buzdar, K. Gelmon, M. Gnant, J. Bonneterre, M. Toi, C. Hudis, J.F.R. Robertson
Journal: Annals of Oncology (2012)
Precocious puberty in a boy with a widespread linear epidermal naevus
Authors: CELIA MOSS, J.M. PARKIN, J.S. COMAISH
Journal: British Journal of Dermatology (1991)

Journal Article Precocious puberty in a boy with a widespread linear epidermal naevus Get access CELIA MOSS, CELIA MOSS Department of Dermatology, Royal Victoria Infirmary. neweastle upon Tyne NEI 4LP. U.K. Dr. C. Moss, Department of Dermatology, The General Hospital, Birmingham B4 6NH. U.K. Search for other works by this author on: Oxford Academic Google Scholar J.M. PARKIN, J.M. PARKIN Department of Paediatries, Royal Victoria Infirmary. neweastle upon Tyne NEI 4LP. U.K. Search for other works by this author on: Oxford Academic Google Scholar J.S. COMAISH J.S. COMAISH Department of Dermatology, Royal Victoria Infirmary. neweastle upon Tyne NEI 4LP. U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue 2, 1 August 1991, Pages 178–182, https://doi.org/10.1111/j.1365-2133.1991.tb06068.x Published: 01 August 1991
Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage.
Authors: G Poli, A L Kinter, J S Justement, P Bressler, J H Kehrl, A S Fauci
Journal: The Journal of Experimental Medicine (1991)

The pleiotropic immunoregulatory cytokine transforming growth factor beta (TGF-beta) potently suppresses production of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome, in the chronically infected promonocytic cell line U1. TGF-beta significantly (50-90%) inhibited HIV reverse transcriptase production and synthesis of viral proteins in U1 cells stimulated with phorbol myristate acetate (PMA) or interleukin 6 (IL-6). Furthermore, TGF-beta suppressed PMA induction of HIV transcription in U1 cells. In contrast, TGF-beta did not significantly affect the expression of HIV induced by tumor necrosis factor alpha (TNF-alpha). These suppressive effects were not mediated via the induction of interferon alpha (IFN-alpha). TGF-beta also suppressed HIV replication in primary monocyte-derived macrophages infected in vitro, both in the absence of exogenous cytokines and in IL-6-stimulated cultures. In contrast, no significant effects of TGF-beta were observed in either a chronically infected T cell line (ACH-2) or in primary T cell blasts infected in vitro. Therefore, TGF-beta may play a potentially important role as a negative regulator of HIV expression in infected monocytes or tissue macrophages in infected individuals.
Susceptibility to nontuberculous mycobacterial lung disease
Authors: P. Sexton, A. C. Harrison
Journal: European Respiratory Journal (2008)

The nontuberculous mycobacteria (NTM) exhibit heterogeneous pathogenicity in humans. Articles on known and potential human factors capable of producing susceptibility to NTM lung disease (NTMLD) were identified by a systematic search of the medical literature, and are reviewed in the present study. Patients with pre-existing structural lung disease are known to be at risk of NTMLD. Other susceptible groups have become recognised since the 1980s, in particular middle-aged nonsmokers without previous lung disease (a group including those with Lady Windermere syndrome) and patients with genetically determined defects of cell-mediated immunity, including abnormalities of the interleukin-12/interferon-γ axis, certain human leukocyte antigen alleles, cystic fibrosis transmembrane conductance regulator mutations, and polymorphisms of solute carrier 11A1 (or natural resistance-associated macrophage protein 1) and the vitamin D receptor. Information is also accruing about acquired systemic causes of susceptibility to NTMLD, including inhibitory antibodies directed against interferon-γ, post-menopausal waning of endogenous oestrogen levels, coeliac disease and exposure to use of dietary phyto-oestrogens. It is not known whether immunosuppressive factors, such as oral corticosteroid treatment, chronic renal failure, diabetes mellitus and other known risk factors for pulmonary tuberculosis, are also risk factors for the development of NTMLD. Caution is appropriate in managing such patients.
Neural Stem Cells
Authors: Rossella Galli, Angela Gritti, Luca Bonfanti, Angelo Luigi Vescovi
Journal: Circulation Research (2003)

This review focuses on the nature and functional properties of stem cells of the adult mammalian central nervous system (CNS). It has recently been shown that cell turnover, including neurons, does occur in the mature CNS, thanks to the persistence of precursor cells that possess the functional characteristics of bona-fide neural stem cells (NSCs) within restricted brain areas. We discuss how the subventricular zone of the forebrain (SVZ) is the most active neurogenetic area and the richest source of NSCs. These NSCs ensure a life-long contribution of new neurons to the olfactory bulb and, when placed in culture, can be grown and extensively expanded for months, allowing the generation of stem cell lines, which maintain stable and constant functional properties. A survey of the differentiation potential of these NSCs, both in vitro and in vivo, outlines their extreme plasticity that seems to outstretch the brain boundaries, so that these neuroectodermal stem cells may give rise to cells that derive from developmentally distinct tissues. A critical discussion of the latest, controversial findings regarding this surprising phenomenon is provided.
Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study
Authors: Tudor Ciuleanu, Thomas Brodowicz, Christoph Zielinski, Joo Hang Kim, Maciej Krzakowski, Eckart Laack, Yi-Long Wu, Isabel Bover, Stephen Begbie, Valentina Tzekova, Branka Cucevic, Jose Rodrigues Pereira, Sung Hyun Yang, Jayaprakash Madhavan, Katherine P Sugarman, Patrick Peterson, William J John, Kurt Krejcy, Chandra P Belani
Journal: The Lancet (2009)
Two Isoforms of the Mouse <i>Ether-a-go-go</i> –Related Gene Coassemble to Form Channels With Properties Similar to the Rapidly Activating Component of the Cardiac Delayed Rectifier K <sup>+</sup> Current
Authors: Barry London, Matthew C. Trudeau, Kimberly P. Newton, Anita K. Beyer, Neal G. Copeland, Debra J. Gilbert, Nancy A. J enkins, Carol A. Satler, Gail A. Robertson
Journal: Circulation Research (1997)

Abstract HERG , the human ether-a-go-go –related gene, encodes a K + -selective channel with properties similar to the rapidly activating component of the delayed rectifier K + current ( I Kr ). Mutations of HERG cause the autosomal-dominant long-QT syndrome (LQTS), presumably by disrupting the normal function of I Kr . The current produced by HERG is not identical to I Kr , however, and the mechanism by which HERG mutations cause LQTS remains uncertain. To better define the role of Erg in the heart, we cloned Merg1 from mouse genomic and cardiac cDNA libraries. Merg1 has 16 exons and maps to mouse chromosome 5 in an area syntenic to human chromosome 7q, the map locus of HERG . We isolated three cardiac isoforms of Merg1 : Merg1a is homologous to HERG and is expressed in heart, brain, and testes, Merg1a′ lacks the first 59 amino acids of Merg1a and is not expressed abundantly, and Merg1b has a markedly shorter divergent N-terminal cytoplasmic domain and is expressed specifically in the heart. The Merg1 isoforms, like HERG, produce inwardly rectifying E-4031–sensitive currents when heterologously expressed in Xenopus oocytes. Merg1a and HERG produce currents with slow deactivation kinetics, whereas Merg1a′ and Merg1b currents deactivate more rapidly. Merg1b coassembles with Merg1a to form channels with deactivation kinetics that are more rapid than those of Merg1a or HERG and nearly identical to I Kr . In addition, a homologue of Merg1b is present in human cardiac and smooth muscle. Thus, we have identified a novel N-terminal Erg isoform that is expressed specifically in the heart, has rapid deactivation kinetics, and coassembles with the longer isoform in Xenopus oocytes. This N-terminal Erg isoform may determine the properties of I Kr and contribute to the pathogenesis of LQTS.
The role of TGFBI (βig-H3) in gastrointestinal tract tumorigenesis
Authors: Bing Han, Haolei Cai, Ying Chen, Bing Hu, Hongyu Luo, Yulian Wu, Jiangping Wu
Journal: Molecular Cancer (2015)

TGFβ-induced (TGFBI/βig-H3) is a protein inducible by TGFβ1 and secreted by many types of cells. It binds to collagen, forms part of the extracellular matrix (ECM), and interacts with integrins on cell surfaces. In this study, we investigated the role of TGFBI in tumorigenesis and the underlying mechanisms.Patient serum TGFBI levels were determined by ELISA. TGFBI transgenic and gene knockout mice and TGFBI-overexpressing liver cells were used for mechanistic studies.We demonstrated that patients with cholangiocarcinomas, hepatic carcinomas or gastric carcinomas presented significantly elevated serum TGFBI levels, and the excess TGFBI was derived from the tumor masses. TGFBI overexpression in mice resulted in increased incidence of spontaneous tumors and N,N-diethylnitrosamine (DEN)-induced liver tumor nodules, compared to that in wild type (WT) mice, while TGFBI knockout mice were comparable to WT controls in these 2 aspects. TGFBI promoted the survival of Aml-12 liver cells with DNA damage after irradiation, and augmented their post-irradiation proliferation. It activated the FAK/AKT/AKT1S1/PRS6/EIF4EBP pathway, which is known to modulate cell survival and proliferation.Our data suggest that TGFBI functions as a promoter of certain gastrointestinal tract cancers. It provides a survival advantage to cells with DNA damage. Over a long time span, this advantage could translate into increased tumor risks.