tbuckley/cabot-search huggingface dataset:
Abstract 5134: G-Quadruplex structure formation in the proximal promoter region of the human vascular endothelial growth factor gene
Authors: Prashansa Agrawal, Emmanuel Hatzakis, Kexiao Guo, Danzhou Yang
Journal: Cancer Research (2011)

Abstract The human vascular endothelial growth factor gene, VEGF, is a key regulator of angiogenesis. It plays an important role in tumor survival, growth and metastasis. It is over-expressed in many types of human cancers including glioma and renal cell carcinoma, ovarian and pancreatic cell carcinomas. The VEGF proximal promoter region contains a poly G/poly C rich tract that is essential for basal and inducible VEGF expression. The guanine-rich (G-rich) strand on this tract is shown to form a specific secondary structure, the G-quadruplex. Here we have elucidated the solution structure of the major intramolecular G-quadruplex formed on the G-rich strand of this region in K+ solution by proton Nuclear Magnetic Resonance (NMR) spectroscopy followed by the structural calculation of the G-quadruplex using Distance Geometry Simulated Annealing (DGSA) module of XPLOR-NIH software. It is inferred that this strand adopts a well-defined parallel-stranded G-quadruplex structure, which contains three G-tetrads stabilized by Hoogsteen hydrogen bonding, as well as three double-chain reversal loops containing 1:4:1 bases, a feature important for the formation of the most thermodynamically stable conformation. The size of the 4-base loop plays a critical role in determining the most favored folded pattern of a G-quadruplex. These 4-base loop residues interact with the residues of the 3’ flanking region of VEGF sequence; also, the 1-base double-chain reversal loop on two edges of the tetrad are very stable, which overall contribute in stabilizing the 1:4:1 conformer. We have found that the two cytosines in this central 4-base loop are involved in hydrogen bonding with the 3’ terminal end residues of VEGF, which is a salient feature as this interaction is sequence-specific and differs from that in other parallel-stranded structures, e.g. c-myc, significantly. These results are also supported by the DMS footprinting results by Guo et al. (2008) which show that the guanines involved in the tetrad formation in this major G-quadruplex loop isomer 1:4:1 are well-protected against DMS methylation. Therefore, the knowledge about the secondary structure of this non B-DNA conformation of the VEGF promoter region is essential for using the G- quadruplex as a target for anticancer drugs, which could be a novel approach to anti-angiogenesis drug discovery in cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5134. doi:10.1158/1538-7445.AM2011-5134
Positron emission tomography detects metabolic viability in myocardium with persistent 24-hour single-photon emission computed tomography 201Tl defects.
Authors: R C Brunken, F V Mody, R A Hawkins, C Nienaber, M E Phelps, H R Schelbert
Journal: Circulation (1992)

BACKGROUND Four-hour 201Tl redistribution images underestimate myocardial viability in patients with coronary artery disease (CAD). Because 4-hour defects often redistribute late, delayed imaging may enhance assessment of tissue viability. Myocardial metabolic activity was therefore assessed with positron emission tomography (PET) in 26 CAD patients with impaired ventricular function (ejection fraction, 32.1 +/- 13.9%) and 24-hour single-photon emission computed tomography (SPECT) 201Tl defects. METHODS AND RESULTS On circumferential profile analysis, PET ischemia was defined by preserved glucose metabolism in hypoperfused myocardium, and PET infarction was defined by concordant reductions in perfusion and metabolism. On 19 stress-redistribution and seven rest-redistribution SPECT studies, four observers visually scored 201Tl activity in eight segments on a scale from 0 (normal) to 3 (complete defect). Using an improvement in visual score &gt; or = 0.75 to define redistribution, there were 100 fixed, 17 partially reversible, and 12 completely reversible defects. PET identified tissue metabolic activity in 51 (51%) segments with fixed defects (21 PET ischemia, 30 PET normal) and nine (53%) segments with partially reversible defects (five PET ischemia, four PET normal). When grouped by 24-hour score, the proportion of fixed defects with metabolic activity varied from 84% (scores &lt; or = 1.4) to 15% (scores &gt; 2.6). For partially reversible defects, only 53% with scores &lt; 2.0 and one of two with scores &gt; or = 2.0 were considered metabolically viable on PET. Of 12 completely reversible defects, six (50%) were normal, five (42%) had PET ischemia, and one (8%) had PET infarction. The proportion of fixed defects with metabolic activity did not depend on whether a rest or stress study was performed or on the change in visual score used to define 201Tl redistribution (0.25, 0.50, 0.75, and 1.00). CONCLUSIONS In CAD patients, PET identifies glucose metabolic activity in the majority of fixed 24-hour 201Tl defects. However, very severe (near-complete) 24-hour 201Tl defects are less likely to exhibit metabolic activity on PET imaging than are defects with less-pronounced reductions in segmental 201Tl activity.
GLOBAL LONGITUDINAL STRAIN AS A PREDICTOR OF SUDDEN CARDIAC DEATH AND DEATH FROM OTHER CAUSES IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Mads K. Ersboll, Fawaz Alenezi, Hyeon Yoon, Zainab Samad, Joseph Kisslo, Phillip Schulte, Linda Shaw, Lars Kober, Eric Velazquez
Journal: Journal of the American College of Cardiology (2014)
Beyond DSM-IV Bereavement Exclusion Criterion E for Major Depressive Disorder
Authors: Guy Chouinard, Virginie-Anne Chouinard, Emmanuelle Corruble
Journal: Psychotherapy and Psychosomatics (2010)

a Department of Psychiatry, Clinical Psychopharmacology, McGill University Health Centre, Montreal, Que. , Canada; b Department of Psychiatry, Saint-Antoine Hospital, Paris , and c Department of Psychiatry, INSERM U669, Paris XI University, Bicetre University Hospital, Assistance Publique-Hopitaux de Paris, Le Kremlin Bicetre , France; d Massachusetts General Hospital/McLean Adult Psychiatry Residency Training Program, Harvard Medical School, Boston, Mass. , USA
Effects of Lisinopril and Nifedipine on the Progression to Overt Albuminuria in IDDM Patients With Incipient Nephropathy and Normal Blood Pressure
Authors: Gaetano Crepaldi, Quirico Carta, Giacomo Deferrari, Ruggero Mangili, Renzo Navalesi, Fausto Santeusanio, Antonio Spalluto, Alessandro Vanasia, G Marco Villa, Romano Nosadini
Journal: Diabetes Care (1998)

Intervention trials on renal function in IDDM patients with microalbuminuria (MA) should adopt the rate of decline of glomerular filtration rate (GFR) as an outcome measure. However, normotensive IDDM patients with MA show no change in GFR over a follow-up period of 10 years. Thus, in the present study, we used the cumulative incidence of progression to albuminuria (albumin excretion rate [AER] > 200 micrograms/min) from MA as the primary endpoint and the yearly increase in AER at a rate of 50% above baseline as the secondary end-point of renal function.Ninety-two normotensive IDDM patients underwent double-blind, double-dummy treatment with either lisinopril or slow-release nifedipine in comparison with placebo. Ten patients discontinued the study during the 3-year follow-up period.During the 3-year follow-up period, 7 of 34 placebo-treated (20.6%), 2 of 32 lisinopril-treated (6.3%), and 2 of 26 nifedipine-treated (7.7%) patients progressed to clinical albuminuria (Fisher's exact test, P < 0.03). Time-to-event analysis indicated a reduction in the risk of progression to macroalbuminuria of 58.1% (95% CI 27.8-68.4%) in the 32 patients on lisinopril (P < 0.02) and of 62.5% (95% CI 32.5-73.4%) in the 26 patients on nifedipine (P < 0.02) after adjustment for mean blood pressure, glycated hemoglobin, and baseline AER in comparison with the 34 patients on placebo. Baseline AER was 71 micrograms/min (range: 20.7-187.3) in progressors and 73 micrograms/min (range: 20.2-174.1) in nonprogressors (NS). The percentage of patients who showed a > 50% yearly increase of AER above baseline values was significantly lower in the lisinopril group (13 of 32, 40.6%, P < 0.02), but not in the nifedipine group (15 of 26, 57.7%), than in the placebo group (23 of 34, 67.6%). The lisinopril group had significantly lower blood pressure values during follow-up than either the nifedipine (P < 0.05) or the placebo (P < 0.01) group.Our data show that both lisinopril and nifedipine are effective in delaying the occurrence of macroalbuminuria in normotensive IDDM patients with MA. As overt proteinuria strongly predicts end-stage renal failure, both treatments appear capable of preventing such a complication in normotensive IDDM patients with MA. However, lisinopril appears more powerful in slowing the course of nephropathy.
Vacuum Aspiration of the Uterus in Therapeutic Abortion
Authors: A. E. R. Buckle, M. M. Anderson, K. C. Loung
Journal: BMJ (1970)

A prospective study of vacuum aspiration in 400 cases of therapeutic abortion is described showing that the procedure was quick, involving little blood loss in most cases, and that the complication rate was low. The routine use of this method in therapeutic abortion is recommended.
Chrysotile in water
Authors: Sidney Speil
Journal: Environmental Health Perspectives (1974)

The problems of quantitating chrysotile in water by fiber count techniques are reviewed briefly and the use of mass quantitation is suggested as a preferable measure. Chrysotile fiber has been found in almost every sample of natural water examined, but generally transmission electron miscroscopy (TEM) is required because of the small diameters involved. The extreme extrapolation required in mathematically converting a few fibers or fiber fragments under the TEM to the fiber content of a liquid sample casts considerable doubt on the validity of numbers used to compare chrysotile contents of different liquids.
Is Cost Containment for Real?
Authors: Eli Ginzberg
Journal: JAMA (1986)

"ETHOS vs. Exigencies: Medicine's Dilemma" was the theme of the tenth Annual Symposium of Blue Cross-Blue Shield of Illinois, held Oct 18, 1985, in Chicago. There were four participants in the opening session entitled "Managing the Cost of Care—The Key to Survival"; I was assigned the anchor role. Representative Daniel Rostenkowski, the first presenter, argued in favor of his proposal that Congress impose a ceiling of $300 per month on tax-free health benefits, emphasizing that only 5% of all families would be adversely affected. In his view, this was a much more reasonable approach than that of the President, who recommended taxing the first $25 of any employer contribution, a plan that, the Chairman of the Ways and Means Committee pointed out, "nobody in the Administration or out defends... as good politics or good health policy."<sup>1(p2)</sup> C. McClain Haddow, acting administrator of the Health Care Financing Administration, next sang
Abstract 4670: Identification of common genetic variants contributing to cisplatin-induced apoptosis and cytotoxicity in lymphoblastoid cell lines
Authors: Lidija K. Gorsic, Amy L. Stark, Heather E. Wheeler, Hae K. Im, M. Eileen Dolan
Journal: Cancer Research (2012)

Abstract Cisplatin is a platinum agent effective against head and neck, ovarian, cervical, testicular, and lung cancers; however, severe toxicities and intrinsic/acquired resistance hinder its utility. Identifying genetic variants to predict patients at risk for toxicity or non-response would be highly beneficial. To this end, we utilized lymphoblastoid cell lines (LCLs) to identify variants associated with cisplatin-induced cytotoxicity (cell growth inhibition) and apoptosis (caspase 3/7 activity). International HapMap LCLs derived from populations of Northern and Western European (CEU), African (YRI), and African-American (ASW) ancestry were phenotyped for cell growth inhibition and caspase 3/7 activity followed by Genome Wide Association Studies (GWAS). Analysis revealed expression quantitative trait loci (eQTL) enrichment in cytotoxicity-associated SNPs (p&amp;lt;0.001) and in apoptosis-associated SNPs (p&amp;lt;0.001) for all population sets. Applying a threshold of p&amp;lt;0.001 resulted in 19, 14, 0, and 1 SNP(s) overlapping in CEU, YRI, ASW, and meta analysis combining the 3 populations respectively. Furthermore, we found that 16/19 and 9/14 overlapping SNPs for CEU and YRI are eQTLs. Of the 16 eQTLs in CEU, rs4343077 correlated with cisplatin-induced cytotoxicity (p=0.0007) and apoptosis (p=0.0007) and is intronic of epidermal growth factor receptor pathway substrate 8 (EPS8). Given that EPS8 encodes an oncoprotein participating in malignant transformation of tumor cells and has been formerly linked to cisplatin-induced drug response, we evaluated cellular sensitivity to cisplatin following siRNA knockdown in 5 CEU LCLs. Successful knockdown of greater than 70% of endogenous EPS8 resulted in a 7% increase in percent survival (p=1e-6) and a 6.6% decrease for caspase 3/7 activity (p=0.033) across cell lines. We also evaluated expression levels of 6 target genes of rs4343077 and found that 5 significantly (p&amp;lt;0.01) changed following EPS8 knockdown. Our genome wide approach evaluating both cytotoxicity and apoptosis led to the identification of EPS8, a gene that confers sensitivity to cisplatin. Identification of genetic variants contributing to cisplatin-induced cell death through apoptosis is necessary for a better mechanistic understanding of the drug and ultimately to identify patients most likely to respond. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4670. doi:1538-7445.AM2012-4670
Cell-mediated Immune Response in Primary Biliary Cirrhosis to a Protein Fraction from Human Bile
Authors: A. L. W. F. Eddleston, I. G. McFarlane, C. G. Mitchell, W. D. Reed, R. Williams
Journal: BMJ (1973)

Cell-mediated immune responses to a protein fraction of human bile have been demonstrated, using the leucocyte migration test, in eight out of 10 patients with primary biliary cirrhosis but in only three out of nine with active chronic hepatitis. In the latter condition sensitization to a liver-specific hepatocellular antigen was found more frequently (five out of nine patients) than in primary biliary cirrhosis (two out of 10). These results, as well as the granuloma formation observed histologically, suggest that the initial bile duct lesion in primary biliary cirrhosis may be associated with a cell-mediated response to antigens—perhaps derived from bile duct epithelial cells—which may be normal constituents of hepatic bile.
18F-FDG PET/CT Findings in Voltage-Gated Potassium Channel Limbic Encephalitis
Authors: Koramadai Karuppuswamy Kamaleshwaran, Rajesh Shankar Iyer, None Joppy Antony, Edathuruthy Kalarickal Radhakrishnan, Ajit Shinto
Journal: Clinical Nuclear Medicine (2013)

Limbic encephalitis (LE) can be associated with cancer, viral infection, or be idiopathic. One such rare but treatable form is associated with voltage-gated potassium channel (VGKC) antibodies. Typical abnormalities are seen in FDG PET/CT. We report a 39-year-old female patient who presented with 3 months of progressive faciobrachial dystonic seizures and limbic encephalitis. Her serum and cerebrospinal fluid Lgi1 antibody titers were elevated. FDG PET/CT showed basal ganglial hypermetabolism and associated abnormalities. Serial MRI demonstrated atrophic changes predominantly involving the temporal lobes. She is on immunosuppressive therapy and shows clinical improvement with lowering of antibody titers.
Risk of fatal accidents occurring other than at sea among Icelandic seamen.
Authors: V Rafnsson, H Gunnarsdottir
Journal: BMJ (1993)

OBJECTIVE--To study mortality among seamen, particularly from fatal accidents that occurred other than at sea. DESIGN--Cohort study. SETTING--Iceland. SUBJECTS--27,884 seamen, both fishermen and sailors from the merchant fleet, who had been members of a pension fund from 1958 to 1986. MAIN OUTCOME MEASURES--Cause of death (ICD seventh revision), standardised mortality ratio. RESULTS--Most standardised mortality ratios were greater than 1, being 1.26 for all causes and 1.83 for all external causes. There was no healthy worker effect. The excess of deaths from all external causes included all subcategories of death from accidents, poisonings, and violence and not just accidents at sea (water transport accidents, ICD codes E850-E858). A significant trend was found for length of employment and mortality from all accidents at sea, drowning at sea, accidental poisoning, other accidents, and accidental drowning; correlation coefficients for all causes, all accidents, suicide, and injuries undetermined whether accidentally or purposely inflicted were 0.7-0.8. Compared with seamen who started work during 1968-77, those who started work in 1978 or later had higher mortality from all causes, road traffic accidents, poisoning, other accidents, homicide, and injuries unknown whether accidentally or purposely inflicted, but not from all accidents at sea and accidental drowning. CONCLUSION--Seamen seem to be a special group with a high risk of fatal accidents occurring not only at sea. The association between fatal accidents other than at sea and length of employment as seamen indicates that seamen are modified by their occupation towards hazardous behaviour or a risky lifestyle.
Noscapine Crosses the Blood-Brain Barrier and Inhibits Glioblastoma Growth
Authors: Jaren W. Landen, Vincent Hau, Mingshen Wang, Thomas Davis, Brian Ciliax, Bruce H. Wainer, Erwin G. Van Meir, Johnathan D. Glass, Harish C. Joshi, David R. Archer
Journal: Clinical Cancer Research (2004)

Abstract The opium alkaloid noscapine is a commonly used antitussive agent available in Europe, Asia, and South America. Although the mechanism by which it suppresses coughing is currently unknown, it is presumed to involve the central nervous system. In addition to its antitussive action, noscapine also binds to tubulin and alters microtubule dynamics in vitro and in vivo. In this study, we show that noscapine inhibits the proliferation of rat C6 glioma cells in vitro (IC50 = 100 μm) and effectively crosses the blood-brain barrier at rates similar to the ones found for agents such as morphine and [Met]enkephalin that have potent central nervous system activity (P ≤ 0.05). Daily oral noscapine treatment (300 mg/kg) administered to immunodeficient mice having stereotactically implanted rat C6 glioblasoma into the striatum revealed a significant reduction of tumor volume (P ≤ 0.05). This was achieved with no identifiable toxicity to the duodenum, spleen, liver, or hematopoietic cells as determined by pathological microscopic examination of these tissues and flow cytometry. Furthermore, noscapine treatment resulted in little evidence of toxicity to dorsal root ganglia cultures as measured by inhibition of neurite outgrowth and yielded no evidence of peripheral neuropathy in animals. However, evidence of vasodilation was observed in noscapine-treated brain tissue. These unique properties of noscapine, including its ability to cross the blood-brain barrier, interfere with microtubule dynamics, arrest tumor cell division, reduce tumor growth, and minimally affect other dividing tissues and peripheral nerves, warrant additional investigation of its therapeutic potential.
Abnormal metabolism of arachidonic acid in chronic inflammatory bowel disease: enhanced release of leucotriene B4 from activated neutrophils.
Authors: O H Nielsen, I Ahnfelt-Ronne, J Elmgreen
Journal: Gut (1987)

The metabolism of endogenous arachidonic acid P(AA) was investigated in activated neutrophils from 20 patients with Crohn9s disease, 20 with ulcerative colitis, and 25 healthy volunteers. 1-14C-P(AA) was incorporated into intracellular pools of phospholipids prior to activation of the cells with ionophore A23187 and analyses of released arachidonic acid metabolites by thin layer chromatography. Total release of radioactivity expressing the release of arachidonic acid and its metabolites, was equal in the experimental and control groups, which suggests a normal substrate availability. In contrast, there was a marked increase in the relative release of leucotriene B4 (LTB4) and its omega-oxidation products, 20-hydroxy-LTB4 (20-OH-LTB4) and 20-carboxy-LTB4 (20-COOH-LTB4), with LTB4 values exceeding the reference interval in seven of 20 patients with Crohn9s disease, median 8.7%, and in six of 20 patients with ulcerative colitis, median 7.7%, as compared with a median of 5.3% in healthy volunteers. Furthermore, a decreased release of unmetabolised arachidonic acid, correlating inversely with the release of LTB4 in all experimental and control groups, and normal values for the production of other metabolites of arachidonic acid--for example, 5-hydroxyeicosatetraenoic acid (5-HETE) and 12-hydroxyheptadecatrienoic acid (HHT), point to an enzymatic abnormality such as increased activity of leucotriene B synthetase. An increased capacity for release of LTB4, the major pro-inflammatory metabolite of arachidonic acid lipoxygenation by polymorphonuclear leucocytes, may contribute to perpetuation of the inflammation and to tissue destruction in chronic inflammatory bowel disease. Our findings agree with previous reports of an increased release of LTB4 by the colonic mucosa in this condition.
Myocardial Hypertrophic Preconditioning Attenuates Cardiomyocyte Hypertrophy and Slows Progression to Heart Failure Through Upregulation of S100A8/A9
Authors: Xuan Wei, Bing Wu, Jing Zhao, Zhi Zeng, Wanling Xuan, Shiping Cao, Xiaobo Huang, Masanori Asakura, Dingli Xu, Jianping Bin, Masafumi Kitakaze, Yulin Liao
Journal: Circulation (2015)

Background— Transient preceding brief ischemia provides potent cardioprotection against subsequent long ischemia, termed ischemic preconditioning. Here, we hypothesized that transient short-term hypertrophic stimulation would induce the expression of hypertrophy regression genes and render the heart resistant to subsequent hypertrophic stress, and slow the progression to heart failure, as well. Methods and Results— Cardiomyocyte hypertrophy was induced in mice by either transverse aortic constriction or an infusion of phenylephrine, and in neonatal rat ventricular cardiomyocytes by norepinephrine exposures. In the preconditioning groups, hypertrophic stimulation was provided for 1 to 7 days and then withdrawn for several days by either aortic debanding or discontinuing phenylephrine or norepinephrine treatment, followed by subsequent reexposure to the hypertrophic stimulus for the same period as in the control group. One or 6 weeks after transverse aortic constriction, the heart weight/body weight ratio was lower in the preconditioning group than in the control group, whereas the lung weight/body weight ratio was significantly decreased 6 weeks after transverse aortic constriction. Similar results were obtained in mice receiving phenylephrine infusion and neonatal rat ventricular cardiomyocytes stimulated with norepinephrine. Both mRNA and protein expression of S100A8 and S100A9 showed significant upregulation after the removal of hypertrophic stimulation and persisted for 6 weeks in response to reimposition of transverse aortic constriction. The treatment with recombinant S100A8/A9 inhibited norepinephrine-induced myocyte hypertrophy and reduced the expression of calcineurin and NFATc3, but the silencing of S100A8/A9 prevented such changes. Conclusions— Preconditioning with prohypertrophic factors exerts an antihypertrophic effect and slows the progression of heart failure, indicating the existence of the phenomenon for hypertrophic preconditioning.