tbuckley/cabot-search huggingface dataset:
Increased Inducible Nitric Oxide Synthase Expression Contributes to Myocardial Dysfunction and Higher Mortality After Myocardial Infarction in Mice
Authors: Qingping Feng, Xiangru Lu, Douglas L. Jones, Ji Shen, J. Malcolm O. Arnold
Journal: Circulation (2001)

Background — Inducible nitric oxide synthase (iNOS) is expressed in the myocardium after myocardial infarction (MI) and in heart failure. Its pathophysiological role in these conditions, however, is not clear. We hypothesized that increased NO production from iNOS expression causes myocardial dysfunction and results in higher mortality after MI. Methods and Results — MI was induced by left coronary artery ligation in iNOS −/− mutant and wild-type mice. Mortality was followed up for 30 days. MI resulted in a significant increase in mortality in both iNOS −/− and wild-type mice compared with sham operation ( P &lt;0.01). Mortality was significantly decreased and LV myocardial contractility was increased, however, in iNOS −/− mice compared with the wild-type mice ( P &lt;0.05). Five days after MI, myocardial iNOS mRNA expression, plasma nitrate and nitrite concentrations, and myocardial and plasma nitrotyrosine levels were significantly increased in wild-type compared with iNOS −/− mutant mice ( P &lt;0.05). Both basal LV +dP/dt and its response to dobutamine were significantly increased in iNOS −/− compared with the wild-type mice ( P &lt;0.05). Conclusions — Increased NO production from iNOS expression contributes to myocardial dysfunction and mortality after MI in mice.
Reperfusion Strategies in Acute Coronary Syndromes
Authors: Akshay Bagai, George D. Dangas, Gregg W. Stone, Christopher B. Granger
Journal: Circulation Research (2014)

The appropriate timing of angiography to facilitate revascularization is essential to optimize outcomes in patents with ST-segment–elevation myocardial infarction and non–ST-segment–elevation acute coronary syndromes. Timely reperfusion of the infarct-related coronary artery in ST-segment–elevation myocardial infarction both with fibrinolysis or percutaneous coronary intervention minimizes myocardial damage, reduces infarct size, and decreases morbidity and mortality. Primary percutaneous coronary intervention is the preferred reperfusion method if it can be performed in a timely manner. Strategies to reduce health system–related delays in reperfusion include regionalization of ST-segment–elevation myocardial infarction care, performing prehospital ECGs, prehospital activation of the catheterization laboratory, bypassing geographically closer nonpercutaneous coronary intervention–capable hospitals, bypassing the percutaneous coronary intervention–capable hospital emergency department, and early and consistent availability of the catheterization laboratory team. With implementation of such strategies, there has been significant improvement in process measures, including door-to-balloon time. However, despite reductions in door-to-balloon times, there has been little change during the past several years in in-hospital mortality, suggesting additional factors including patient-related delays, optimization of tissue-level perfusion, and cardioprotection must be addressed to improve patient outcomes further. Early angiography followed by revascularization when appropriate also reduces rates of death, MI, and recurrent ischemia in patients with non–ST-segment–elevation acute coronary syndromes, with the greatest benefits realized in the highest risk patients. Among patients with non–ST-segment–elevation acute coronary syndromes with multivessel disease, choice of revascularization modality should be made as in stable coronary artery disease, with a goal of complete ischemic revascularization.
The Relevance of PET in Diagnostic Oncology
Authors: E. Bombardieri, A. Alessi, C. Villano, A. Gerali, F. Crippa
Journal: Clinical Nuclear Medicine (2008)

The characteristic feature of nuclear medicine is that it provides functional images of organs, tissues and both normal and pathological processes, revealing the uptake and the biodistribution of several radiopharmaceuticals according to their pathway of flux, concentration and metabolism. There is a strong relationship between nuclear medicine and oncology since in general nuclear medicine images are able to give both morphological information and data on molecular and cellular activity. The major advantages of this functional imaging are that this biological characterization is carried out by the direct observation in vivo of the patient ().
Stretch Activates Nitric Oxide Production in Pulmonary Vascular Endothelial Cells <i>In Situ</i>
Authors: Wolfgang M. Kuebler, Ulrike Uhlig, Torsten Goldmann, Gregor Schael, Alexander Kerem, Kay Exner, Christian Martin, Ekkehard Vollmer, Stefan Uhlig
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Whereas endothelial responses to shear stress have been studied extensively, the responses to circumferential vascular stretch are yet poorly defined. Circumferential stretch in pulmonary microvessels is largely determined by the transmural pressure gradient, hence by both vascular perfusion and alveolar ventilation pressures. Here, we have studied the production of nitric oxide (NO) by the endothelial nitric oxide synthase (eNOS) in two different models of vascular stretch in the intact lung: In isolated-perfused rat lungs, vascular stretch was induced by elevation of vascular pressure. In situ digital fluorescence microscopy revealed stretch-dependent NO production, which was localized to capillary endothelial cells and inhibited by NOS blockers. In isolated-perfused mouse lungs, vascular stretch was generated by ventilation with elevated negative pressure. Stretch-induced phosphorylation of Akt and eNOS in lung endothelial cells was demonstrated by immunohistochemistry and increased NO production by in situ fluorescence microscopy. Stretch-induced endothelial responses in both models were abrogated by pretreatment with phosphatidylinositol-3-OH kinase inhibitors. These findings demonstrate that circumferential stretch activates NO production in pulmonary endothelial cells by a signaling cascade involving phosphatidylinositol-3-OH kinase, Akt, and eNOS and that this response is independent from the mechanical factors causing vascular distension.
Structure of the bc1 Complex from Seculamonas ecuadoriensis, a Jakobid Flagellate with an Ancestral Mitochondrial Genome
Authors: Stefanie Marx, Maja Baumgärtner, Sivakumar Kannan, Hans-Peter Braun, B Franz Lang, Gertraud Burger, Sivakumar Kunnan
Journal: Molecular Biology and Evolution (2003)

In eubacteria, the respiratory bc1 complex (complex III) consists of three or four different subunits, whereas that of mitochondria, which have descended from an α-proteobacterial endosymbiont, contains about seven additional subunits. To understand better how mitochondrial protein complexes evolved from their simpler bacterial predecessors, we purified complex III of Seculamonas ecuadoriensis, a member of the jakobid protists, which possess the most bacteria-like mitochondrial genomes known. The S. ecuadoriensis complex III has an apparent molecular mass of 460 kDa and exhibits antimycin-sensitive quinol:cytochrome c oxidoreductase activity. It is composed of at least eight subunits between 6 and 46 kDa in size, including two large "core" subunits and the three "respiratory" subunits. The molecular mass of the S. ecuadoriensisbc1 complex is slightly lower than that reported for other eukaryotes, but about 2× as large as complex III in bacteria. This indicates that the departure from the small bacteria-like complex III took place at an early stage in mitochondrial evolution, prior to the divergence of jakobids. We posit that the recruitment of additional subunits in mitochondrial respiratory complexes is a consequence of the migration of originally α-proteobacterial genes to the nucleus.
Ectopic lymphoid tissue alters the chemokine gradient, increases lymphocyte retention and exacerbates murine ileitis
Authors: Eóin N McNamee, Joanne C Masterson, Paul Jedlicka, Colm B Collins, Ifor R Williams, Jesús Rivera-Nieves
Journal: Gut (2012)

Background The earliest endoscopically-evident lesion in Crohn's disease is the aphthous ulcer, which develops over ectopic lymphoid tissues (ie, inducible lymphoid follicles (ILF), tertiary lymphoid tissue (TLT)) in the chronically inflamed intestine. ILF/TLT are induced within effector sites by homeostatic lymphoid chemokines, but their role in the development of intestinal ILF/TLT and in the pathogenesis of Crohn's disease is poorly understood. Design Using a mouse model of Crohn's-like ileitis (TNF∆ARE) which develops florid induction of ILF/TLT within its terminal ileum, the contribution of the CCR7/CCL19/CCL21 chemokine axis during the development of TLT and its role in disease pathogenesis were assessed. Results Both CCL19 and CCL21 were increased within the inflamed ileum of TNF∆ARE mice, which resulted in CCR7 internalisation and impaired T cell chemotaxis. ILF/TLT were a major source of CCL19 and CCL21 and increased local synthesis, augmented recruitment/retention of effector, naïve and central memory T cell subsets within the inflamed ileum. Immunoblockade of CCR7 resulted in further effector T cell retention and exacerbation of ileitis. Conclusions Induction of ILF/TLT in the chronically inflamed intestine alters the homeostatic CCL19-CCL21 lymphoid-chemokine gradient and increases recruitment/retention of effector CCR7+ T cell subsets within the terminal ileum, contributing to the perpetuation of chronic inflammation. Thus, blockade of CCR7 or its ligands might result in deleterious consequences for subjects with chronic inflammatory diseases.
17β-Estradiol Reduces Cardiomyocyte Apoptosis In Vivo and In Vitro via Activation of Phospho-Inositide-3 Kinase/Akt Signaling
Authors: Richard D. Patten, Isaac Pourati, Mark J. Aronovitz, Jason Baur, Flore Celestin, Xin Chen, Ashour Michael, Syed Haq, Simone Nuedling, Christian Grohe, Thomas Force, Michael E. Mendelsohn, Richard H. Karas
Journal: Circulation Research (2004)

Female gender and estrogen-replacement therapy in postmenopausal women are associated with improved heart failure survival, and physiological replacement of 17β-estradiol (E2) reduces infarct size and cardiomyocyte apoptosis in animal models of myocardial infarction (MI). Here, we characterize the molecular mechanisms of E2 effects on cardiomyocyte survival in vivo and in vitro. Ovariectomized female mice were treated with placebo or physiological E2 replacement, followed by coronary artery ligation (placebo-MI or E2-MI) or sham operation (sham) and hearts were harvested 6, 24, and 72 hours later. After MI, E2 replacement significantly increased activation of the prosurvival kinase, Akt, and decreased cardiomyocyte apoptosis assessed by terminal deoxynucleotidyltransferase dUTP nick-end labeling (TUNEL) staining and caspase 3 activation. In vitro, E2 at 1 or 10 nmol/L caused a rapid 2.7-fold increase in Akt phosphorylation and a decrease in apoptosis as measured by TUNEL staining, caspase 3 activation, and DNA laddering in cultured neonatal rat cardiomyocytes. The E2-mediated reduction in apoptosis was reversed by an estrogen receptor (ER) antagonist, ICI 182,780, and by phospho-inositide-3 kinase inhibitors, LY294002 and Wortmannin. Overexpression of a dominant negative-Akt construct also blocked E2-mediated reduction in cardiomyocyte apoptosis. These data show that E2 reduces cardiomyocyte apoptosis in vivo and in vitro by ER- and phospho-inositide-3 kinase–Akt–dependent pathways and support the relevance of these pathways in the observed estrogen-mediated reduction in myocardial injury.
Cross-National Study of Diagnosis of the Mental Disorders: Origin of the Problem
Authors: MORTON KRAMER
Journal: American Journal of Psychiatry (1969)

Many investigators have noted the large differences that have persisted over the years between the rates of first admissions to the mental hospitals of England and Wales and those of the U. S. for affective disorders, schizophrenia, and psychosis with cerebral arteriosclerosis. The author describes the background and complexity of the problem and the efforts leading up to the present research project, aimed at explaining the differences.
Method of preparing isolated colonic epithelial cells (colonocytes) for metabolic studies.
Authors: W E Roediger, S C Truelove
Journal: Gut (1979)

Suspensions of isolated colonic epithelial cells (colonocytes) have been obtained from rats by incubating everted lengths of colon with EDTA at 37 degrees C in Krebs-Henseleit saline from which calcium was omitted and containing 0.25% (w/v) bovine serum albumin. Measurements of oxygen consumption and lactate production by cell suspensions indicate that they are metabolically active for at least one hour. The method has been modified for the preparation of isolated epithelial cells from the human colon by including an enzyme digestion step and by increasing the concentration of EDTA to 10 mM. Human colonocytes have been obtained either from normal mucosa (ascending and descending colon) or from the mucosa in ulcerative colitis (descending colon). Oxygen consumption of human cell suspensions is lower than in the rat but in colonocytes from both species the rate is increased by glucose and by n-butyrate, a normal constituent of the colonic lumen. The method yields metabolically active cell suspensions from diseased colonic mucosa and promises to be of value for biochemical studies of ulcerative colitis.
DNA Microarray Technology: Devices, Systems, and Applications
Authors: Michael J. Heller
Journal: Annual Review of Biomedical Engineering (2002)

In this review, recent advances in DNA microarray technology and their applications are examined. The many varieties of DNA microarray or DNA chip devices and systems are described along with their methods for fabrication and their use. This includes both high-density microarrays for high-throughput screening applications and lower-density microarrays for various diagnostic applications. The methods for microarray fabrication that are reviewed include various inkjet and microjet deposition or spotting technologies and processes, in situ or on-chip photolithographic oligonucleotide synthesis processes, and electronic DNA probe addressing processes. The DNA microarray hybridization applications reviewed include the important areas of gene expression analysis and genotyping for point mutations, single nucleotide polymorphisms (SNPs), and short tandem repeats (STRs). In addition to the many molecular biological and genomic research uses, this review covers applications of microarray devices and systems for pharmacogenomic research and drug discovery, infectious and genetic disease and cancer diagnostics, and forensic and genetic identification purposes. Additionally, microarray technology being developed and applied to new areas of proteomic and cellular analysis are reviewed.
Slower Postnatal Growth Is Associated with Delayed Cerebral Cortical Maturation in Preterm Newborns
Authors: Jillian Vinall, Ruth E. Grunau, Rollin Brant, Vann Chau, Kenneth J. Poskitt, Anne R. Synnes, Steven P. Miller
Journal: Science Translational Medicine (2013)

Impaired growth during neonatal intensive care is associated with delayed microstructural development of the cortical gray matter after accounting for prenatal growth, neonatal illness, and brain injury in infants born very preterm.
Association Between Hyperglycemia and Survival in Patients With Newly Diagnosed Glioblastoma
Authors: Rachel L. Derr, Xiaobu Ye, Melissa U. Islas, Serena Desideri, Christopher D. Saudek, Stuart A. Grossman
Journal: Journal of Clinical Oncology (2009)

Hyperglycemia has been associated with poor outcomes in many disease states. This retrospective study assessed the association between hyperglycemia and survival in patients with newly diagnosed glioblastoma multiforme (GBM). PATIENTS AND METHODS; Between 1999 and 2004, before the standard use of temozolomide, 191 patients were accrued onto New Approaches to Brain Tumor Therapy CNS Consortium trials with similar eligibility criteria. Time-weighted mean glucose and mean glucocorticoid dose were calculated for each patient using all values collected regularly in follow-up. The primary outcome was survival.Mean glucose levels ranged between 65 and 459 mg/dL. These were divided into quartiles: quartile one (< 94 mg/dL), quartile two (94 to 109 mg/dL), quartile three (110 to 137 mg/dL), and quartile four (> 137 mg/dL). Median survival times for patients in quartiles one, two, three, and four were 14.5, 11.6, 11.6, and 9.1 months, respectively. The association between higher mean glucose and shorter survival persisted after adjustment for mean daily glucocorticoid dose, age, and baseline Karnofsky performance score (KPS). Compared with patients in the lowest mean glucose quartile, those in quartile two (adjusted hazard ratio [HR], 1.29; 95% CI, 0.85 to 1.96), quartile three (adjusted HR, 1.35; 95% CI, 0.89 to 2.06), and quartile four (adjusted HR, 1.57; 95% CI, 1.02 to 2.40) were at progressively higher risk of dying (P = .041 for trend).In these patients with newly diagnosed GBM and good baseline KPS, hyperglycemia was associated with shorter survival, after controlling for glucocorticoid dose and other confounders. The effect of intensive management of glucocorticoid-related hyperglycemia on survival deserves additional study in patients with GBM.
Echocardiography as a Noninvasive Swan-Ganz Catheter
Authors: Jae K. Oh
Journal: Circulation (2005)

iwan and co-investigators report in this issue of Circulation that the interval between onset of mitral E and annular early diastolic velocity (Ea) by tissue Doppler, T EϪEa , can be used to estimate left ventricular (LV) filling pressure in patients with mitral valve disease. 1 Garcia and colleagues were the first to report that the onset of Ea occurred 7.5Ϯ3.5 ms after peak mitral inflow velocity in 7 patients with restrictive cardiomyopathy, whereas Ea started 22Ϯ19 ms earlier than did E in the normal group. 2Subsequently, T EϪEa has been shown to correlate with the time constant of LV relaxation () demonstrated by Hasegawa and associates in their elegant animal experiment. 3With worsening of heart failure by rapid pacing, Ea progressively decreased in velocity and delayed in onset.Mitral E occurred coincidently with the termination of the early diastolic left arterial (LA) and LV pressure gradient at baseline and all stages of heart failure.In contrast, with increasing heart failure, Ea was progressively delayed after LA to LV pressure crossover, and T EϪEa was related to .Rivas-Gotz, Nagueh, and their associates also demonstrated that T EϪEa was prolonged after constriction of the circumflex coronary artery in dogs. 4In patients with heart failure, LV myocardial relaxation and compliance are decreased.
FLUORESCENT ANTIBODY DETECTION OF THE ANTIGENS OF THE SHOPE PAPILLOMA VIRUS IN PAPILLOMAS OF THE WILD AND DOMESTIC RABBIT
Authors: Wilbur Fiske Noyes, Robert C. Mellors
Journal: The Journal of Experimental Medicine (1957)

The results obtained by a fluorescent antibody study of the Shope papilloma virus in papillomas of the wild and domestic rabbit are presented. In the wild rabbit papillomas the viral antigens occurred exclusively in the nucleus and were present in the differentiating cells of the keratohyaline layers and in the keratinized layers. The antigens were not present in the deeper proliferating epithelial cells of the papillomas. The Shope viral antigens were present in very minute amounts in papillomas of the domestic rabbit, as compared with papillomas of the wild rabbit, and were only detected in the superficial keratinized layers. It is postulated that virus is present in the nuclei of the proliferating cells of the papillomas of the wild and domestic rabbit but exists there in an early stage of development, consisting mainly of nucleic acid and deficient in protein, therefore non-antigenic and not demonstrable by fluorescent antibody. The nucleic acid moiety of the virus may be infective, and the protein component may provide immunologic specificity and serve to preserve transmissibility. The protein-deficient virus can be referred to as masked virus.
Inhaled Nitric Oxide for Premature Infants with Severe Respiratory Failure
Authors: Krisa P. Van Meurs, Linda L. Wright, Richard A. Ehrenkranz, James A. Lemons, M. Bethany Ball, W. Kenneth Poole, Rebecca Perritt, Rosemary D. Higgins, William Oh, Mark L. Hudak, Abbot R. Laptook, Seetha Shankaran, Neil N. Finer, Waldemar A. Carlo, Kathleen A. Kennedy, Jon H. Fridriksson, Robin H. Steinhorn, Gregory M. Sokol, G. Ganesh Konduri, Judy L. Aschner, Barbara J. Stoll, Carl T. D'Angio, David K. Stevenson
Journal: New England Journal of Medicine (2005)

Inhaled nitric oxide is a controversial treatment for premature infants with severe respiratory failure. We conducted a multicenter, randomized, blinded, controlled trial to determine whether inhaled nitric oxide reduced the rate of death or bronchopulmonary dysplasia in such infants.We randomly assigned 420 neonates, born at less than 34 weeks of gestation, with a birth weight of 401 to 1500 g, and with respiratory failure more than four hours after treatment with surfactant to receive placebo (simulated flow) or inhaled nitric oxide (5 to 10 ppm). Infants with a response (an increase in the partial pressure of arterial oxygen of more than 10 mm Hg) were weaned according to protocol. Treatment with study gas was discontinued in infants who did not have a response.The rate of death or bronchopulmonary dysplasia was 80 percent in the nitric oxide group, as compared with 82 percent in the placebo group (relative risk, 0.97; 95 percent confidence interval, 0.86 to 1.06; P=0.52), and the rate of bronchopulmonary dysplasia was 60 percent versus 68 percent (relative risk, 0.90; 95 percent confidence interval, 0.75 to 1.08; P=0.26). There were no significant differences in the rates of severe intracranial hemorrhage or periventricular leukomalacia. Post hoc analyses suggest that rates of death and bronchopulmonary dysplasia are reduced for infants with a birth weight greater than 1000 g, whereas infants weighing 1000 g or less who are treated with inhaled nitric oxide have higher mortality and increased rates of severe intracranial hemorrhage.The use of inhaled nitric oxide in critically ill premature infants weighing less than 1500 g does not decrease the rates of death or bronchopulmonary dysplasia. Further trials are required to determine whether inhaled nitric oxide benefits infants with a birth weight of 1000 g or more.
Nucleoside Analogs Plus Ritonavir in Stable Antiretroviral Therapy–Experienced HIV-Infected Children&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Sharon A. Nachman
Journal: JAMA (2000)

IN EARLY 1997 MANY CHILDREN INfectedwithhumanimmunodeficiency virus (HIV) were receiving single or dual nucleoside analog therapy and were clinically and immunologically stable, 1,2 despite increasing plasma HIV RNA levels.However, the availability of protease inhibitors and their demonstrated success in adults raised the question of how they should be used in children.Pediatric AIDS Clinical Trials Group (PACTG) Protocol 338 was undertaken to evaluate the safety, tolerance, and virologic efficacy of changing from current antiretroviral treatment in clinically and immunologically stable, protease inhibitor-naive children to either dual nucleoside analog therapy or a 2or 3-drug regimen containing a protease inhibitor, ritonavir.Current antiretroviral guidelines for treatment of HIV-infected children and
Burkitt’s Lymphoma and Previous AIDS-Defining Illnesses Are Not Prognostic Factors in AIDS-Related Non-Hodgkin’s Lymphoma
Authors: Justin Stebbing, Sundhiya Mandalia, Carlo Palmieri, Mark Nelson, Brian Gazzard, Mark Bower
Journal: Journal of Clinical Oncology (2005)

risk rather than absolute difference assumptions.Nevertheless, these calculations may be helpful for clinical understanding and discussion if not for formal inference or comparison.