tbuckley/cabot-search huggingface dataset:
Pivotal role of Cu,Zn-superoxide dismutase in endothelium-dependent hyperpolarization
Authors: Keiko Morikawa, Hiroaki Shimokawa, Tetsuya Matoba, Hiroshi Kubota, Takaaki Akaike, M.A. Hassan Talukder, Makoto Hatanaka, Takako Fujiki, Hiroshi Maeda, Shosuke Takahashi, Akira Takeshita
Journal: Journal of Clinical Investigation (2003)

The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several vasodilating factors, including prostacyclin, NO, and endothelium-derived hyperpolarizing factor (EDHF). We have recently identified that endothelium-derived H2O2 is an EDHF in mesenteric arteries of mice and humans and in porcine coronary microvessels. However, the mechanism for the endothelial production of H2O2 as an EDHF remains to be elucidated. In this study, we tested our hypothesis that Cu,Zn-superoxide dismutase (Cu,Zn-SOD) plays a pivotal role in endothelium-dependent hyperpolarization, using control and Cu,Zn-SOD–/– mice. In mesenteric arteries, EDHF-mediated relaxations and hyperpolarizations were significantly reduced in Cu,Zn-SOD–/– mice with no inhibitory effect of catalase, while endothelium-independent relaxations and hyperpolarizations were preserved. Endothelial H2O2 production also was significantly reduced in Cu,Zn-SOD–/– mice. In Langendorff isolated heart, bradykinin-induced increase in coronary flow was significantly reduced in Cu,Zn-SOD–/– mice, again with no inhibitory effect of catalase. The exogenous SOD mimetic tempol significantly improved EDHF-mediated relaxations and hyperpolarizations and coronary flow response in Cu,Zn-SOD–/– mice. These results prove the novel concept that endothelial Cu,Zn-SOD plays an important role as an "EDHF synthase" in mice, in addition to its classical role to scavenge superoxide anions.
Fiat lux in understanding cardiac pacing, resynchronization and signalling by way of optogenetics
Authors: E. Entcheva
Journal: Cardiovascular Research (2014)

This editorial refers to ‘Optogenetic activation of Gq signalling modulates pacemaker activity of cardiomyocytes’ by T. Beiert et al. , pp. 507–516, this issue. 

This editorial refers to ‘Modulation of cardiac tissue electrophysiological properties with light-sensitive proteins’ by U. Nussinovitch et al. , 2014;102:176–187. 

Multiple cell types and complex signalling cascades control the generation and regularity of the heartbeat. Understanding their concerted operation in vivo is a challenge that necessitates new technical tools. Optogenetics1,2 uses genetically encoded light-sensitive proteins to both actuate and/or sense fast biological processes in cells, tissues, and in behaving animals.3 The use of light and light-sensitive biological elements, i.e. the ‘optical’ aspect of this approach, enables remote, spatio-temporally precise probing and control; the ‘genetic’ addressing confers cell specificity. While the utility of this technology has been fully embraced in neuroscience research, its extension to the cardiovascular field has been rather slow.4–8 Two recent papers in this journal—by Beiert et al. 9 and by Nussinovitch et al. 10—further contribute to the budding field of cardiac optogenetics.

Most current optogenetic applications deal with direct perturbation of membrane potential, i.e. excitation or inhibition of electrical activity through the expression of light-sensitive ion channels and pumps (opsins), providing inward/excitatory or outward/repolarizing currents. These opsins can be introduced into the heart through development of transgenic cell lines and animals,4,5 direct viral delivery in cardiomyocytes11 or by cell delivery.7 In the latter case, dedicated donor cells, that may not …
Genomic Renal Score for Assessing Risk of Recurrence in Renal Cancer: Subgroup Analyses from the Validation Study
Authors: B. Escudier, S. Koscielny, M. Lopatin, C. Svedman, V. Verkarre, C. Radulescu, Y. Neuzillet, M. Timsit, I. Hemmerlé, T. Tsiatis, M. Bonham, D. Knezevic, T. Lebret, A. Goddard, A. Mejean
Journal: Annals of Oncology (2014)
Many Americans Have Pre-Diabetes and Should Be Considered for Metformin Therapy
Authors: Mary K. Rhee, Kirsten Herrick, David C. Ziemer, Viola Vaccarino, William S. Weintraub, K.M. Venkat Narayan, Paul Kolm, Jennifer G. Twombly, Lawrence S. Phillips
Journal: Diabetes Care (2009)

OBJECTIVE To determine the proportion of the American population who would merit metformin treatment, according to recent American Diabetes Association (ADA) consensus panel recommendations to prevent or delay the development of diabetes. RESEARCH DESIGN AND METHODS Risk factors were evaluated in 1,581 Screening for Impaired Glucose Tolerance (SIGT), 2,014 Third National Health and Nutrition Examination Survey (NHANES III), and 1,111 National Health and Nutrition Examination Survey 2005–2006 (NHANES 2005–2006) subjects, who were non-Hispanic white and black, without known diabetes. Criteria for consideration of metformin included the presence of both impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), with ≥1 additional diabetes risk factor: age &amp;lt;60 years, BMI ≥35 kg/m2, family history of diabetes, elevated triglycerides, reduced HDL cholesterol, hypertension, or A1C &amp;gt;6.0%. RESULTS Isolated IFG, isolated IGT, and IFG and IGT were found in 18.0, 7.2, and 8.2% of SIGT; 22.3, 6.4, and 9.4% of NHANES III; and 21.8, 5.0, and 9.0% of NHANES 2005–2006 subjects, respectively. In SIGT, NHANES III, and NHANES 2005–2006, criteria for metformin consideration were met in 99, 96, and 96% of those with IFG and IGT; 31, 29, and 28% of all those with IFG; and 53, 57, and 62% of all those with IGT (8.1, 9.1, and 8.7% of all subjects), respectively. CONCLUSIONS More than 96% of individuals with both IFG and IGT are likely to meet ADA consensus criteria for consideration of metformin. Because &amp;gt;28% of all those with IFG met the criteria, providers should perform oral glucose tolerance tests to find concomitant IGT in all patients with IFG. To the extent that our findings are representative of the U.S. population, ∼1 in 12 adults has a combination of pre-diabetes and risk factors that may justify consideration of metformin treatment for diabetes prevention.
Hydrogen Peroxide, Potassium Currents, and Membrane Potential in Human Endothelial Cells
Authors: Rostislav Bychkov, Knud Pieper, Christian Ried, Marianna Milosheva, Eugen Bychkov, Friedrich C. Luft, Hermann Haller
Journal: Circulation (1999)

Hydrogen peroxide (H2O2) and reactive oxygen species are implicated in inflammation, ischemia-reperfusion injury, and atherosclerosis. The role of ion channels has not been previously explored.K+ currents and membrane potential were recorded in endothelial cells by voltage- and current-clamp techniques. H2O2 elicited both hyperpolarization and depolarization of the membrane potential in a concentration-dependent manner. Low H2O2 concentrations (0.01 to 0.25 micromol/L) inhibited the inward-rectifying K+ current (KIR). Whole-cell K+ current analysis revealed that H2O2 (1 mmol/L) applied to the bath solution increased the Ca2+-dependent K+ current (KCa) amplitude. H2O2 increased KCa current in outside-out patches in a Ca2+-free solution. When catalase (5000 micro/mL) was added to the bath solution, the outward-rectifying K+ current amplitude was restored. In contrast, superoxide dismutase (1000 u/mL) had only a small effect on the H2O2-induced K+ current changes. Next, we measured whole-cell K+ currents and redox potentials simultaneously with a novel redox potential-sensitive electrode. The H2O2-mediated KCa current increase was accompanied by a whole-cell redox potential decrease.H2O2 elicited both hyperpolarization and depolarization of the membrane potential through 2 different mechanisms. Low H2O2 concentrations inhibited inward-rectifying K+ currents, whereas higher H2O2 concentrations increased the amplitude of the outward K+ current. We suggest that reactive oxygen species generated locally increases the KCa current amplitude, whereas low H2O2 concentrations inhibit KIR via intracellular messengers.
The AAV9 receptor and its modification to improve in vivo lung gene transfer in mice
Authors: Christie L. Bell, Luk H. Vandenberghe, Peter Bell, Maria P. Limberis, Guang-Ping Gao, Kim Van Vliet, Mavis Agbandje-McKenna, James M. Wilson
Journal: Journal of Clinical Investigation (2011)

Vectors based on adeno-associated virus (AAV) serotype 9 are candidates for in vivo gene delivery to many organs, but the receptor(s) mediating these tropisms have yet to be defined. We evaluated AAV9 uptake by glycans with terminal sialic acids (SAs), a common mode of cellular entry for viruses. We found, however, that AAV9 binding increased when terminal SA was enzymatically removed, suggesting that galactose, which is the most commonly observed penultimate monosaccharide to SA, may mediate AAV9 transduction. This was confirmed in mutant CHO Pro-5 cells deficient in the enzymes involved in glycoprotein biogenesis, as well as lectin interference studies. Binding of AAV9 to glycans with terminal galactose was demonstrated via glycan binding assays. Co-instillation of AAV9 vector with neuraminidase into mouse lung resulted in exposure of terminal galactose on the apical surface of conducting airway epithelial cells, as shown by lectin binding and increased transduction of these cells, demonstrating the possible utility of this vector in lung-directed gene transfer. Increasing the abundance of the receptor on target cells and improving vector efficacy may improve delivery of AAV vectors to their therapeutic targets.
No Evidence of Sex-Related Survival Disparities among Head and Neck Cancer Patients Receiving Similar Multidisciplinary Care: A Matched-Pair Analysis
Authors: Jess C. Roberts, Guojun Li, Lorraine R. Reitzel, Qingyi Wei, Erich M. Sturgis
Journal: Clinical Cancer Research (2010)

Abstract Purpose: It is unknown whether there are survival disparities between men and women with squamous cell carcinoma of the head and neck (SCCHN), although some data suggest that men have worse outcomes. We conducted a matched-pair study that controlled for several potentially confounding prognostic variables to assess whether a survival advantage exists for female compared with male SCCHN patients receiving similar care. Experimental Design: We selected 286 female patients and 286 matched male patients from within a prospective epidemiologic study on 1,654 patients with incident SCCHN evaluated and treated at a single large multidisciplinary cancer center. Matching variables included age (±10 y), race/ethnicity, smoking status (never versus ever), tumor site (oral cavity versus oropharynx versus larynx versus hypopharynx), tumor classification (T1-2 versus T3-4), nodal status (negative versus positive), and treatment (surgery, radiation therapy, surgery and radiation therapy, surgery and chemotherapy, chemoradiotherapy, or surgery and chemoradiotherapy). Results: Matched-pair and log-rank analyses showed no significant differences between women and men in recurrence-free, disease-specific, or overall survival. When the analysis was restricted to individual sites (oral cavity, oropharynx, or larynx/hypopharynx), there was also no evidence of a disparity in survival associated with sex. Conclusions: We conclude that there is no evidence to suggest that a survival advantage exists for women as compared with men with SCCHN receiving similar multidisciplinary directed care at a tertiary cancer center. Clin Cancer Res; 16(20); 5019–27. ©2010 AACR.
Melanoptysis as a complication of fibreoptic bronchoscopy
Authors: M J Mena, M J Rodriguez-Nieto, M Gómez, J Flandes, R Melchor
Journal: European Respiratory Journal (1998)

The case is presented of a coal miner with bilateral masses of progressive massive fibrosis, who developed acute cavitation following fibreoptic bronchoscopy and biopsies. Indeed, immediately upon bronchoscopy with transbronchial biopsy, there was expectoration of abundant melanoptysis. Three days later, the chest radiograph showed a cavity and the patient again coughed up black material, in the context of pulmonary infection. One week later, there was complete emptying of the conglomerate mass. To the authors' knowledge, this is the first reported case of a conglomerate mass of progressive massive fibrosis which cavitated as a result of bronchoscopy.
Effect of acute hypoxia on QTc interval in respiratory patients undergoing fitness to fly tests
Authors: J. R. A. Skipworth, Z. Puthucheary, D. A. Raptis, J. Rawal, D. Shrikrishna, J. Windsor, D. Cramer, M. I. Polkey, H. E. Montgomery, N. S. Hopkinson
Journal: Thorax (2010)

individual behaviours of sleepy drivers.Our data, albeit from a limited number of patients with OSAS, support the reliability of a driving simulator approach for the identification of patients with OSAS at risk: poor performers have high risk if they keep on driving when sleepy.Accordingly, poorer simulated driving performance was associated with crash history only in our subjects with 'risky' behaviour.Nevertheless, the use of driving simulators is still recommended as a research tool given the absence of a standardisation that is the prerequisite for use in clinical practice.Finally, crash risk is a multifactorial entity.Even if it is highly influenced by sleepiness, individual behaviours have a prominent effect in letting sleepiness determine a car accident.We emphasise that educational programmes, potentially involving driving simulators in different settings, remain the key instrument for risk management of sleepiness-related car accidents.
Neoadjuvant chemotherapy in stage IIIa non-small cell lung cancer.
Authors: R Milroy, F Macbeth
Journal: Thorax (1995)

Background.The efficacy of surgery for patients with non-small cell lung cancer is limited, although recent studies suggest that preoperative chemotherapy may improve survival.We conducted a randomized trial to examine the possible benefit of preoperative chemotherapy and surgery for the treatment of patients with non-small cell lung cancer.Methods.We studied 60 patients (59 men and 1 woman) with stage IIIA non-small cell lung cancer.The patients were randomly assigned to receive either surgery alone or three courses of chemotherapy (6 mg of mitomycin per square meter of bodysurface area, 3 g of ifosfamide per square meter, and 50 mg of cisplatin per square meter) given intravenously at three-week intervals and followed bysurgery.Allpatients received mediastinal radiation after surgery.The resected tumors were evaluated by means of K-ras oncogene analysis and flow cytometry.Results.The median period o.f survival was 26 months in the patients treated with chemotherapy plus surgery, as compared with 8 months in the patients treated with surgery alone (P<0.001); the median period of disease-free survival was 20 months in the former group, as compared with 5 months in the latter (P<0.001).The rate of recurrence was 56 percent in the group treated with chemotherapy plus surgery and 74 percent in the group treated with surgery alone.The prevalence of mutated K-ras oncogenes was 15 percent among the patients receiving preoperative chemotherapy and 42 percent among those treated with surgery alone (P=0*05).Most of the patients treated with chemotherapy plus surgery had tumors that consisted of diploid cells, whereas the patients treated with surgery alone had tumors with aneuploid cells.Conclusions.Preoperative chemotherapy increases the median survival in patients with non-small cell lung cancer.
Intracellular glucose oxidation and glycogen synthase activity are reduced in non-insulin-dependent (type II) diabetes independent of impaired glucose uptake.
Authors: A W Thorburn, B Gumbiner, F Bulacan, P Wallace, R R Henry
Journal: Journal of Clinical Investigation (1990)

To examine whether reduced rates of oxidative (Gox) and non-oxidative (Nox) glucose metabolism in non-insulin-dependent diabetes mellitus (NIDDM) are due to reduced glucose uptake, intrinsic defects in intracellular glucose metabolism or increased fat oxidation (Fox), indirect calorimetry was performed at similar glucose uptake rates in eight nonobese NIDDM and eight comparable nondiabetic subjects. Three glucose clamp studies were performed: one in the nondiabetic and two in the NIDDM subjects. In the nondiabetic subjects, glucose uptake was increased to 7.62 +/- 0.62 mg/kg of fat-free mass (FFM) per min by increasing serum insulin to 309 pmol/liter at a glucose concentration of 5.1 mmol/liter. By raising the concentration of either serum glucose or insulin fourfold in the NIDDM subjects, glucose uptake was matched to nondiabetic subjects (8.62 +/- 0.49 and 8.59 +/- 0.51 mg/kg FFM per min, respectively, P = NS). Skeletal muscle glycogen synthase activity and plasma lactate levels were measured to characterize Nox. When glucose uptake was matched to nondiabetics by hyperglycemia or hyperinsulinemia, Gox was reduced by 26-28% in NIDDM (P less than 0.025) whereas Fox was similar. Nox was greater in NIDDM (P less than 0.01) and was accompanied by increases in circulating lactate levels. Glycogen synthase activity was reduced by 41% (P less than 0.025) when glucose uptake was matched by hyperglycemia. Glycogen synthase activity was normalized in NIDDM, however, when glucose uptake was matched by hyperinsulinemia. Therefore, a defect in Gox exists in nonobese NIDDM subjects which cannot be overcome by increasing glucose uptake or insulin. Since both glucose uptake and Fox were similar in the two subject groups these factors were not responsible for reduced Gox. Increased Nox in NIDDM is primarily into lactate. Reduced glycogen synthase activity in NIDDM is independent of glucose uptake but can be overcome by increasing the insulin concentration.
The National Academy of Medicine’s Vision
Authors: Victor J. Dzau
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Comparison of surgical and medical management of bleeding peptic ulcers.
Authors: K D Vellacott, M W Dronfield, M Atkinson, M J Langman
Journal: BMJ (1982)

During 1975-80, 908 patients admitted to Nottingham hospitals with gastrointestinal bleeding and found to have gastric or duodenal ulcers were analysed retrospectively for short-term outcome of treatment. Overall one-quarter of all patients underwent operation, but when the years 1975-7 were compared with 1978-80 the operation rate fell from one in three to just over one in five. Death rates were much lower in patients treated medically than in those who underwent operation, and the risks of operation were greater for patients with gastric ulcer. Less conventional operations were attended by greater mortality. Almost all patients who died during medical treatment and three-quarters of those who died after operation were over 65. No differences in age or clear variations in haemoglobin concentrations or transfusion requirements were found between the earlier and later periods. Reduction in operation rates had no appreciable effect on mortality, despite the accepted view that early operation is advisable.
Interleukin 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition.
Authors: S Okusawa, J A Gelfand, T Ikejima, R J Connolly, C A Dinarello
Journal: Journal of Clinical Investigation (1988)

In addition to activating T and B lymphocytes, interleukin 1 (IL-1) induces several hematologic and metabolic changes typical of host responses to infection and injury. We now report a new biological property, namely, the induction of hypotension. Rabbits given a single intravenous injection of recombinant human IL-1-beta (5 micrograms/kg) rapidly developed decreased systemic arterial pressure, which reached the lowest levels after 50-60 min and slowly returned to pre-IL-1 values after 3 h. Associated with the hypotension, systemic vascular resistance and central venous pressure fell, while cardiac output and heart rate increased. These responses were prevented by ibuprofen given 15 min before the IL-1. A bolus injection of IL-1 followed by a 2-h infusion sustained the hypotension and was associated with leukopenia and thrombocytopenia. Ibuprofen given at the mid-point of the infusion reversed the changes in all hemodynamic parameters, but had no effect on the leukopenia or thrombocytopenia. Tumor necrosis factor (TNF) also induced a shock-like state in rabbits. When the dose of IL-1 or TNF was reduced to 1 microgram/kg, no hemodynamic changes were observed; however, the combination of these low doses of both cytokines resulted in a profound shock-like state including histological evidence of severe pulmonary edema and hemorrhage. Pretreatment with ibuprofen prevented the hemodynamic, leukocyte, and platelet changes induced by the low-dose cytokine combination, and ameliorated the pulmonary tissue damage. These results demonstrate that IL-1, like TNF, possesses the ability to induce hemodynamic and hematological changes typical of septic shock, and that the combination of IL-1 and TNF is more potent than either agent alone. These effects seem to require cyclooxygenase products, and suggest that intravenous cyclooxygenase inhibitors may be of therapeutic value in patients with IL-1/TNF-mediated shock.