tbuckley/cabot-search huggingface dataset:
Nitrite Potently Inhibits Hypoxic and Inflammatory Pulmonary Arterial Hypertension and Smooth Muscle Proliferation via Xanthine Oxidoreductase–Dependent Nitric Oxide Generation
Authors: Brian S. Zuckerbraun, Sruti Shiva, Emeka Ifedigbo, Michael A. Mathier, Kevin P. Mollen, Jayashree Rao, Philip M. Bauer, Justin J.W. Choi, Erin Curtis, Augustine M.K. Choi, Mark T. Gladwin
Journal: Circulation (2009)

Background— Pulmonary arterial hypertension is a progressive proliferative vasculopathy of the small pulmonary arteries that is characterized by a primary failure of the endothelial nitric oxide and prostacyclin vasodilator pathways, coupled with dysregulated cellular proliferation. We have recently discovered that the endogenous anion salt nitrite is converted to nitric oxide in the setting of physiological and pathological hypoxia. Considering the fact that nitric oxide exhibits vasoprotective properties, we examined the effects of nitrite on experimental pulmonary arterial hypertension. Methods and Results— We exposed mice and rats with hypoxia or monocrotaline-induced pulmonary arterial hypertension to low doses of nebulized nitrite (1.5 mg/min) 1 or 3 times a week. This dose minimally increased plasma and lung nitrite levels yet completely prevented or reversed pulmonary arterial hypertension and pathological right ventricular hypertrophy and failure. In vitro and in vivo studies revealed that nitrite in the lung was metabolized directly to nitric oxide in a process significantly enhanced under hypoxia and found to be dependent on the enzymatic action of xanthine oxidoreductase. Additionally, physiological levels of nitrite inhibited hypoxia-induced proliferation of cultured pulmonary artery smooth muscle cells via the nitric oxide–dependent induction of the cyclin-dependent kinase inhibitor p21 Waf1/Cip1 . The therapeutic effect of nitrite on hypoxia-induced pulmonary hypertension was significantly reduced in the p21-knockout mouse; however, nitrite still reduced pressures and right ventricular pathological remodeling, indicating the existence of p21-independent effects as well. Conclusion— These studies reveal a potent effect of inhaled nitrite that limits pathological pulmonary arterial hypertrophy and cellular proliferation in the setting of experimental pulmonary arterial hypertension.
Diagnostic accuracy of a serotype-specific antigen test in community-acquired pneumonia
Authors: Susanne M. Huijts, Michael W. Pride, Josephine M.I. Vos, Kathrin U. Jansen, Chris Webber, William Gruber, Wim G. Boersma, Dominic Snijders, Jan A.J.W. Kluytmans, Ivo van der Lee, Bart A.F. Kuipers, Arie van der Ende, Marc J.M. Bonten
Journal: European Respiratory Journal (2013)

Our aim was to evaluate the diagnostic accuracy and clinical utility of a serotype-specific urinary antigen detection multiplex assay for identification of 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) in urine of patients with community-acquired pneumonia. Adult patients with clinical suspicion of community-acquired pneumonia were included. In addition to standard diagnostic procedures, a urine sample was collected to perform the urinary antigen detection test. Demographic, clinical, radiological and microbiological data were collected. Among 1095 community-acquired pneumonia patients Streptococcus pneumoniae was identified as causative pathogen in 257 (23%), when using conventional diagnostic methods and in 357 (33%) when urinary antigen detection was added. Of the 49 bacteraemic episodes caused by one of the 13 serotypes covered by the urinary antigen detection, 48 were detected by the urinary antigen detection, indicating a sensitivity of 98%. Of the 77 community-acquired pneumonia episodes with a “non-urinary antigen detection” causative pathogen, none had a positive urinary antigen detection result, indicating a specificity of 100%. Addition of the urinary antigen detection test to conventional diagnostic methods increased the prevalence of S. pneumoniae community-acquired pneumonia by 39%. Using bacteraemic episodes as reference sensitivity and specificity of the urinary antigen detection was 98% and 100%, respectively.
Low-Dose Amiodarone for Maintenance of Sinus Rhythm After Cardioversion of Atrial Fibrillation or Flutter
Authors: A T Gosselink, H J Crijns, I C Van Gelder, H Hillige, A C Wiesfeld, K I Lie
Journal: JAMA (1992)

To study efficacy and safety of low-dose amiodarone for maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation or flutter.Nonrandomized trial; mean duration of follow-up, 20.7 months.Referral center; institutional practice; both hospitalized and ambulatory care.Eighty-nine consecutive patients having chronic atrial fibrillation or flutter and eligible for cardioversion. Patients had failed previous treatment aimed at maintaining sinus rhythm. During follow-up one patient was withdrawn because of side effects; all patients were available for follow-up.Before cardioversion, patients received 600 mg of amiodarone daily during a 4-week loading period. After conversion, the daily maintenance dose was 204 +/- 66 mg (mean +/- SD).Arrhythmia recurrence and adverse effects causing drug discontinuation.During loading, 15 patients (16%) converted, and after electrical cardioconversion, 90% of all patients had sinus rhythm. Actuarially, 53% of these patients were still in sinus rhythm after 3 years. In patients with compromised left ventricular function, 93% maintained sinus rhythm after 6 months. One patient died due to congestive heart failure. Intolerable side effects occurred in one patient. No proarrhythmia was observed. Logistic regression analysis revealed that amiodarone was ineffective in patients with mitral stenosis or chronic arrhythmia.Low-dose amiodarone is effective for maintaining sinus rhythm in patients with difficult to treat chronic atrial fibrillation or flutter and is associated with a low incidence of serious side effects.
The Health Effects of Economic Decline
Authors: Ralph Catalano, Sidra Goldman-Mellor, Katherine Saxton, Claire Margerison-Zilko, Meenakshi Subbaraman, Kaja LeWinn, Elizabeth Anderson
Journal: Annual Review of Public Health (2011)

Political pronouncements and policy statements include much conjecture concerning the health and behavioral effects of economic decline. We both summarize empirical research concerned with those effects and suggest questions for future research priorities. We separate the studies into groups defined by questions asked, mechanisms invoked, and outcomes studied. We conclude that although much research shows that undesirable job and financial experiences increase the risk of psychological and behavioral disorder, many other suspected associations remain poorly studied or unsupported. The intuition that mortality increases when the economy declines, for example, appears wrong. We note that the research informs public health programming by identifying risk factors, such as job loss, made more frequent by economic decline. The promise that the research would identify health costs and benefits of economic policy choices, however, remains unfulfilled and will likely remain so without stronger theory and greater methodological agreement.
Mechanisms Underlying the Comorbidity Between Depressive and Addictive Disorders in Adolescents: Interactions Between Stress and HPA Activity
Authors: Uma Rao, Constance L. Hammen, Russell E. Poland
Journal: American Journal of Psychiatry (2009)

Depression may be a precursor to substance use disorder in some youngsters, and substance abuse might complicate the subsequent course of depression. This study examined whether hypothalamic-pituitary-adrenal (HPA) activity and stressful life experiences are related to the development of substance use disorder in depressed and nondepressed adolescents, and whether substance use disorder predicts a worsening course of depression.Urinary-free cortisol was measured for 3 nights in 151 adolescents with no prior history of substance use disorder (55 depressed, 48 at high risk for depression, and 48 normal subjects). Information was obtained on recent stressful life experiences. The participants were followed for up to 5 years to assess the onset of substance use disorder, course of depression, and stressful experiences. The relationships among depression, cortisol as a measure of HPA activity, stressful experiences, and substance use disorder were examined.Elevated cortisol was associated with onset of substance use disorder. Stressful life experiences moderated this relationship. Cortisol and stress accounted for the effects of a history or risk of depression on the development of substance use disorder. Substance use disorder was associated with higher frequency of subsequent depressive episodes.Higher cortisol prior to the onset of substance use disorder may indicate vulnerability to substance use disorder. Stressful experiences increase the risk for substance use disorder in such vulnerable youth. The high prevalence of substance use disorders in depressed individuals may be explained, in part, by high levels of stress and increased HPA activity.
A Land Plant–Specific Multigene Family in the Unicellular Mesostigma Argues for Its Close Relationship to Streptophyta
Authors: Aurora M. Nedelcu, Tudor Borza, Robert W. Lee
Journal: Molecular Biology and Evolution (2006)

The search for the unicellular relative of Streptophyta (i.e., land plants and their closest green algal relatives, the charophytes) started many years ago and remained centered around the scaly green flagellate, Mesostigma viride. To date, despite numerous studies, the phylogenetic position of Mesostigma is still debated and the nature of the unicellular ancestor of Streptophyta remains unknown. As molecular phylogenetic studies have produced conflicting results, we constructed a M. viride expressed sequence tags library and searched for sequences that are shared between M. viride and the Streptophyta (to the exclusion of the other green algal lineages—the Chlorophyta). Here, we report a multigene family that is restricted to Streptophyta and M. viride. The phylogenetic distribution of this complex character and its potential involvement in the evolution of an important land plant adaptive trait (i.e., three-dimensional tissues) argue that Mesostigma is a close unicellular relative of Streptophyta.
The oncoprotein H-RasV12 increases mitochondrial metabolism
Authors: Sucheta Telang, Andrew N Lane, Kristin K Nelson, Sengodagounder Arumugam, Jason Chesney
Journal: Molecular Cancer (2007)

Abstract Background Neoplastic cells increase glycolysis in order to produce anabolic precursors and energy within the hypoxic environment of a tumor. Ras signaling is activated in several cancers and has been found to regulate metabolism by enhancing glycolytic flux to lactate. We examined the effects of sequential immortalization and H-Ras V12 -transformation of human bronchial epithelial cells on the anabolic fate of fully-labeled 13 C-glucose-derived carbons using two-dimensional total correlated spectroscopic analysis-nuclear magnetic resonance spectroscopy (2D TOCSY-NMR). Results We found that the introduction of activated H-Ras V12 into immortalized human bronchial epithelial cells unexpectedly increased tricarboxylic acid cycle activity as measured by the direct conversion of 13 C-glucose carbons into the anabolic substrates glutamate/glutamine, aspartate and uridine. We then observed that immortalization and H-Ras V12 -transformation of bronchial epithelial cells caused a stepwise increase in oxygen consumption, a global measure of electron transport chain activity. Importantly, ectopic expression of H-Ras V12 sensitized immortalized cells to the ATP-depleting and cytotoxic effects of electron transport perturbation using the complex I inhibitor rotenone. Conclusion Taken together, these data indicate that the oncoprotein H-Ras V12 increases mitochondrial metabolism and provide new rationale for the targeting of the tricarboxylic acid cycle and electron transport chain as anti-neoplastic strategies.
BIOACTIVE COMPOUNDS IN NUTRITION AND HEALTH-RESEARCH METHODOLOGIES FOR ESTABLISHING BIOLOGICAL FUNCTION: The Antioxidant and Anti-inflammatory Effects of Flavonoids on Atherosclerosis
Authors: P.M. Kris-Etherton, M. Lefevre, G.R. Beecher, M.D. Gross, C.L. Keen, T.D. Etherton
Journal: Annual Review of Nutrition (2004)

Identifying bioactive compounds and establishing their health effects are active areas of scientific inquiry. There are exciting prospects that select bioactive compounds will reduce the risk of many diseases, including chronic diseases such as cardiovascular disease. Recent findings have established that cardiovascular disease is a disease of inflammation, and consequently is amenable to intervention via molecules that have anti-inflammatory effects. In addition, research demonstrating adverse effects of oxidants on atherogenesis raises the possibility that antioxidants can confer cardioprotective effects. This review provides an overview of research approaches that can be used to unravel the biology and health effects of bioactive compounds. Because of the number of bioactive compounds and the diversity of likely biological effects, numerous and diverse experimental approaches must be taken to increase our understanding of the biology of bioactive compounds. Recognizing the complexity of this biology, sophisticated experimental designs and analytical methodologies must be employed to advance the field. The discovery of novel health effects of bioactive compounds will provide the scientific basis for future efforts to use biotechnology to modify/fortify foods and food components as a means to improve public health.
P197Neuropilin (NRP) 1 hypomorphism combined with defective VEGF-A binding reveals novel roles for NRP1 in developmental and pathological angiogenesis
Authors: I Zachary, A Fantin, B Herzog, M Mahmoud, M Yamaji, A Plein, L Denti, C Ruhrberg
Journal: Cardiovascular Research (2014)

Purpose: Neuropilin 1 (NRP1) is a receptor for class 3 semaphorins and vascular endothelial growth factor A (VEGF) and essential for cardiovascular development. Biochemical evidence supports a model for NRP1 function in which VEGF binding induces complex formation between NRP1 and VEGFR2 to enhance endothelial VEGF signalling. However, the relevance of VEGF binding to NRP1 for angiogenesis in vivo is unclear. We therefore generated knock-in mice expressing Nrp1 with a mutation of tyrosine (Y) 297 in the VEGF binding pocket of the NRP1 b1 domain, a residue previously shown to be important for high affinity VEGF binding and NRP1/VEGFR2 complex formation. Methods: Homozygous NRP1Y297A/Y297A knock-in mice and mouse phenotyping were performed using established previously published methods. Results: Unexpectedly, this targeting strategy also reduced NRP1 expression and therefore generated a NRP1 hypomorph. Despite the loss of VEGF binding and attenuated NRP1 expression, homozygous Nrp1Y297A/Y297A mice were born at normal Mendelian ratios, arguing against NRP1 functioning exclusively as a VEGF164 receptor in embryonic angiogenesis. By overcoming the mid-gestation lethality of full Nrp1-null mice, homozygous Nrp1Y297A/Y297A mice further revealed essential roles for NRP1 in postnatal angiogenesis and arteriogenesis in the heart and retina, pathological neovascularisation of the retina and angiogenesis-dependent tumour growth. Conclusions: The mild embryonic vascular phenotypes combined with the extended viability of Nrp1Y297A/Y297A relative to full and endothelial-specific NRP1 knockout mice clearly demonstrates for the first time that VEGF-binding to NRP1 is not essential for embryonic angiogenesis and therefore that NRP1 functions in embryonic EC predominantly in a VEGF-independent role.
Urotensin-II promotes vascular smooth muscle cell proliferation through store-operated calcium entry and EGFR transactivation
Authors: María Rodríguez-Moyano, Ignacio Díaz, Natalia Dionisio, Xuexin Zhang, Javier Ávila-Medina, Eva Calderón-Sánchez, Mohamed Trebak, Juan Antonio Rosado, Antonio Ordóñez, Tarik Smani
Journal: Cardiovascular Research (2013)

AimsUrotensin-II (UII) is a vasoactive peptide that promotes vascular smooth muscle cells (VSMCs) proliferation and is involved in the pathogenesis of atherosclerosis, restenosis, and vascular remodelling. This study aimed to determine the role of calcium (Ca2+)-dependent signalling and alternative signalling pathways in UII-evoked VSMCs proliferation focusing on store-operated Ca2+ entry (SOCE) and epithelium growth factor receptor (EGFR) transactivation.
Inhibition of Nuclear Factor-κB–Mediated Adhesion Molecule Expression in Human Endothelial Cells
Authors: Jean M. Lockyer, John S. Colladay, Wendy L. Alperin-Lea, Timothy Hammond, Andrew J. Buda
Journal: Circulation Research (1998)

The transcriptional regulatory protein nuclear factor-kappaB (NF-kappaB) participates in the control of gene expression of many modulators of the inflammatory and immune responses, including the adhesion molecules E-selectin and intercellular adhesion molecule-1 (ICAM-1). NF-kappaB is found in the cytoplasm complexed with its inhibitory protein IkappaB. On activation, IkappaB is phosphorylated and degraded, thereby freeing NF-kappaB for translocation to the nucleus. We have generated populations of endothelial cells expressing wild-type and a proteolysis-resistant mutation of IkappaB that is lacking the 36 N-terminal amino acids (IkappaBdeltaN) in order to examine the effects of expression of the mutated IkappaB on tumor necrosis factor-alpha (TNF-alpha)-induced E-selectin and ICAM-1 expression. Wild-type and IkappaBdeltaN were introduced into primary endothelial cells using retrovirus infection followed by selection with G418. The IkappaBdeltaN protein remained at untreated control levels in endothelial cells treated with TNF-alpha and also remained complexed with the NF-kappaB family member p65. Furthermore, TNF-alpha-induced NF-kappaB DNA binding activity was inhibited in the population of endothelial cells expressing IkappaBdeltaN. That population of cells was also refractory to upregulation of E-selectin and ICAM-1 after treatment with TNF-alpha. The use of a truncated IkappaBalpha protein to prevent NF-kappaB-mediated gene expression provides a novel and specific approach for investigating the role of NF-kappaB in processes associated with adhesion molecule expression during inflammation.
TCT-779 Characterization of the Impact of Transcatheter Aortic Valve Implantation on Mitral Regurgitation Regression in High Risk Patients With Aortic Stenosis
Authors: Leor Perl, Mordehay Vaturi, Abid Assali, Alexander Sagie, Adaya Weissler-Snir, Pablo Codner, Katia Orvin, Marina Kupershmidt, Hana Vaknin-Assa, Yaron Shapira, Ran Kornowski
Journal: Journal of the American College of Cardiology (2014)
Lesions of the arytenoid region in a patient with exertional dyspnoea
Authors: A Nagai, H Matsumiya, M Hayashi, T Kanemura, S Yasui, K Konno
Journal: European Respiratory Journal (1993)

A 63 year old woman presented with a 3 year history of exertional dyspnoea. Spirometry suggested extrathoracic airway obstruction (decreased inspiratory flow and saw-tooth pattern of flow-volume curves), and bronchoscopy revealed structural lesions and a trembling motion in the arytenoid region, causing upper airway obstruction on forced respiratory efforts. As there were no abnormal findings other than the lesions, the exertional dyspnoea was probably caused by impaired movement of the arytenoid region.
Biochemical determinations of cholinergic innervation in cerebral arteries.
Authors: V M Florence, J A Bevan
Journal: Circulation Research (1979)

Endogenous choline acetyltransferase (ChAT) activity and high affinity (HA) 3H-choline uptake can be assayed specifically and used to quantify cholinergic neuronal mechanisms. In general, arteries at the base of the brain in the cat and rabbit were distinguished by high and in the dog by lower ChAT activity and 3H-choline levels of uptake. There was a linear relationship between the mean values of the observations from of the two assays on given cerebral arteries from the three species (r = 0.871,P less than 0.001). Since ChAT activity and HA 3H-choline uptake essentially are confined to cholinergic nerve terminals, our results imply that the Circle of Willis and its main branches in the cat, rabbit, and dog are cholinergically innervated.
Effects of supplementation with vitamin C or E on albuminuria, glomerular TGF-beta, and glomerular size in diabetes.
Authors: P A Craven, F R DeRubertis, V E Kagan, M Melhem, R K Studer
Journal: Journal of the American Society of Nephrology (1997)

Oxidant stress and a reduction in antioxidant status, including reduced plasma and tissue ascorbic acid content, occur in diabetic patients and experimental models of diabetes. In this study, the effects of treatment of streptozotocin diabetic rats for 2 mo with vitamin C (10 g/kg body wt/d) or dietary vitamin E (200 mg/kg body wt/d) in the drinking water on urinary albumin excretion, glomerular transforming growth factor (TGF)-beta content, and glomerular size were examined. Treatment of diabetic rats with vitamin C or E had no effect on blood glucose levels compared with that in untreated diabetics (453 +/- 28 g/dl +/- SEM). Body weight, BP, and creatinine clearance rates were not significantly different among the study groups. Kidney weight was significantly higher in all of the diabetic groups compared with age-matched control rats. Treatment with vitamin C, but not vitamin E, significantly reduced kidney weight compared with that in untreated diabetic rats. Immunohistochemical staining for TGF-beta was 2.5-fold higher in glomeruli of cortical sections from untreated diabetic rats versus control rats. Treatment with vitamin C or E prevented the increase in glomerular TGF-beta immunoreactivity. Glomerular volume was also significantly increased (twofold) in kidneys of untreated diabetic rats compared with control rats, as assessed by light microscopy. Treatment with vitamin C prevented and treatment with vitamin E reduced the increase in glomerular volume. Treatment with vitamin C also prevented the sevenfold increase in albumin clearance otherwise seen in untreated diabetic rats. By contrast, treatment with vitamin E had no effect on albumin clearance despite reductions in glomerular size and TGF-beta. Renal cortical vitamin E and plasma, but not renal cortical vitamin C, were reduced in diabetic rats versus control rats. Supplementation of diabetic rats with vitamin C markedly increased plasma and renal cortical vitamin C content to values greater than those in control rats. Supplementation with vitamin E increased renal cortical vitamin E content by 50% compared with values in control rats and also increased plasma and renal cortical vitamin C. These results support the potential utility of antioxidant treatment for the prevention of renal injury in diabetes.
Phase II study of cisplatin, gemcitabine and 5-fluorouracil in advanced pancreatic cancer
Authors: A. Novarino, I. Chiappino, G.F. Bertelli, A. Heouaine, G. Ritorto, A. Addeo, G. Bellone, M. Merlano, O. Bertetto
Journal: Annals of Oncology (2004)