tbuckley/cabot-search huggingface dataset:
Oxidative Conversion of Isothiocyanates to Isocyanates by Rat Liver
Authors: Mei-Sie Lee
Journal: Environmental Health Perspectives (1994)

This report describes the oxidative metabolism of isothiocyanates to isocyanates catalyzed by rat liver microsomes.Incubation of 2-naphthylisothio- cyanate, microsomes, and NADPH yielded either NN'-di-2-naphthylurea or, on inclusion of 2-aminofluorene in the incubations, N-2-naphthyl-N'-2- fluorenylurea.These ureas were formed by the production of the known genotoxicant, 2-naphthylisocyanate, which reacted with its hydrolysis product, 2-aminonaphthalene, to yield the symmetrical urea, or with 2-aminofluorene to form the mixed urea.Formation of N,N'-di-2-naphthylthiourea was also observed because 2-aminonaphthalene reacted with the substrate.Urea formation was dependent on the microsomes, NADPH, and oxygen.Use of microsomes from rats previously treated with Aroclor 1254 increased urea formation greater than'10-fold.The enzyme activity was inhibited by x-napthoflavone, flavone, or CO, and slightly inhibited by metyrapone, 7-ethoxycoumarin, or SKF-525A.It was not inhibited by methima- zole or paraoxon, suggesting that neither flavin-containing monooxygenase nor hydrolytic enzyme was involved.These data are consistent with a cytochrome P450-dependent, oxidative desulfuration of 2-naphthylisothiocyanate to yield 2-naphthylisocyanate. Further studies with the isomeric 1- naphthylisothiocyanate and the dietary benzylisothiocyanate showed that they can also be metabolized to their isocyanates, as evidenced by the trapping of isocyanates with 2-aminofluorene to form the mixed ureas.
Real‐life impact of COVID‐19 pandemic lockdown on the management of pediatric and adult asthma: A survey by the EAACI Asthma Section
Authors: Ibon Eguiluz‐Gracia, Maarten van den Berge, Cristina Boccabella, Matteo Bonini, Cristiano Caruso, Mariana Couto, FerdaOner Erkekol, Maia Rukhadze, Silvia Sanchez‐Garcia, Stefano del Giacco, Marek Jutel, Ioana Agache
Journal: Allergy (2021)

The restrictions imposed by the COVID-19 pandemic impact heavily the management of chronic diseases like asthma. This study aimed to evaluate the management of adults and children with asthma during COVID-19-related lockdown.A survey was launched by the European Academy of Allergy and Clinical Immunology (EAACI) via e-mail, website, and social media to EAACI members and members of peer societies.The survey was completed by 339 healthcare professionals from 52 countries. 79% of follow-up consultations were replaced by phone calls, whereas 49% of newly referred patients attended the clinic. 62%, 76%, 66%, 76%, and 87% of responders did not conduct spirometry, impulse oscillometry, bronchodilator test, FeNO, or methacholine provocation, respectively, for asthma diagnosis in adults. The numbers were similar for children. 73% of responders based the initial asthma diagnosis and the prescription of inhaled therapy on clinical parameters only. Lung function tests were used in 29% of cases to monitor asthma worsening, and only 56% of participants were recommended to their patients ambulatory peak expiratory flow (PEF) measurements. Using a 1 (not at all) to 5 (very much) scale, the responders considered that the quality of healthcare provided and the patients' asthma status had deteriorated during the lockdown with 3.2 points and 2.8 points, respectively.Collectively, these results suggest that all necessary resources should be allocated to ensure the performance of lung function tests for initial diagnosis, whereas digital remote monitoring should be reinforced for the follow-up of children and adults with asthma.
75P Locally advanced, stage III non-small cell lung cancer: A highly heterogenous patient population
Authors: M.A.S. Soares, S. Gonçalves-Monteiro, L. Antunes, F. Bernardo, S. Figueiredo, M. Borges, M.J. Bento, P.V. Redondo
Journal: Journal of Thoracic Oncology (2021)
Change in liver blood flow and blood content in dogs during direct and reflex alteration of hepatic sympathetic nerve activity.
Authors: J JCarneiro, D EDonald
Journal: Circulation Research (1977)

A mean decrease of 60% in liver blood volume was recorded by a plethysmographic technique during electrical stimulation of the hepatic nerves in anesthetized, vagotomized dogs. A decrease in pressure in the vascularly isolated carotid sinus to 40 mm Hg, from a mean control of 144 mm Hg, decreased liver blood volume by a mean of 16%; arterial blood pressure increased by a mean of 77 mm Hg. Carotid sinus hypotension was accompanied by respective mean increases of 16% and 1.4% in hepatic arterial and portal venous blood flows, and of 45% and 22% in arterial and portal resistances. Increase in sinus pressure to 240 mm Hg increased liver blood volume by a mean of 20%; arterial blood pressure decreased by 90 mm Hg. Sinus hypertension was accompanied by respective mean decreased of 10% and 1.5% in hepatic arterial and portal venous blood flows, and of 44% and 18% in arterial and portal resistances. Interruption of afferent vagal traffic from cardiopulmonary receptors was maximally effective in decreasing liver b...
Effects of duration and severity of arterial hypertension and cardiac hypertrophy on coronary vasodilator reserve.
Authors: R DWangler, K GPeters, M LMarcus, R JTomanek
Journal: Circulation Research (1982)

Cardiac hypertrophy is associated with a decrease in coronary reserve. However, factors which may modulate the interaction between myocardial growth and vascular proliferation, such as duration and severity of hypertrophy, have not been evaluated. We measured myocardial perfusion with microspheres in conscious, chronically instrumented. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats at 3, 7, and 15 months of age; and in SHR stroke-prone (SHR-SP) rats at 13-14 months of age. Myocardial perfusion was measured with microspheres in awake rats at rest and during maximal coronary dilation produced by dipyridamole infusion (2.0 mg/kg per min, iv). Arterial pressure was significantly elevated (P less than or equal to 0.05) in all hypertensive groups (vs. age-matched WKY), both at rest and during dipyridamole infusion. Left ventricular mass in the SHR rats was increased significantly (P less than or equal to 0.05) by 14%, 28%, and 29% at 3, 7, and 15 months, respectively. Left ventricular mass in the...
The cardiac conduction system in situs ambiguus.
Authors: D FDickinson, J LWilkinson, K RAnderson, ASmith, S YHo, R HAnderson
Journal: Circulation (1979)

The cardiac specialized conduction tissue was studied by serial sectioning in 13 cases of situs ambiguus. In four cases of right isomerism, we found paired sinus nodes in relation to a crista terminalis, and in each case a sling of conduction tissue between two atrioventricular nodes was present regardless of the ventricular morphology or cardiac position. In the cases with left isomerism, the sinus node was hypoplastic and abnormally located. We saw two types of atrioventricular conduction systems. In the three cases in which the morphologically right ventricle lay to the right of the morphologically left ventricle (presumed d-loop), a single atrioventricular bundle arose from a normally located atrioventricular node. In the five cases in which the morphologically right ventricle lay to the left of the morphologically left ventricle (presumed l-loop) and in the one case with a univentricular heart, paired atrioventricular nodes were present, linked or potentially linked by a sling of conduction tissue.
Top-resolution frequency analysis of electrocardiogram with adaptive frequency determination. Identification of late potentials in patients with coronary artery disease.
Authors: RHaberl, H FSchels, PSteinbigler, GJilge, GSteinbeck
Journal: Circulation (1990)

Frequency analysis of the electrocardiogram with Fourier transform is a sensitive method of detecting late potentials. However, information about localization of late potentials is lost, frequency resolution is poor, and window functions have to be applied. We therefore analyzed multiple segments (25 msec long) of the surface electrocardiogram (spectrotemporal mapping) with adaptive frequency determination (AFD), an autoregressive algorithm that is characterized by high-frequency resolution in very short segments without the use of window functions. Results were compared with those from Fourier transform and the Simson method. We studied 38 patients after myocardial infarction (MI) with sustained ventricular tachycardia (VT), 21 patients after MI without VT, and 18 healthy subjects. Frequency peaks could be clearly differentiated until a minimal interval of 6 Hz; with fast Fourier transform (Blackman Harris window) in a much longer segment (80 msec), the spectral peaks merged into one another at an inte...
Asymptotic slope of log pressure vs log volume as an approximate index of the diastolic elastic properties of the myocardium in man.
Authors: J DLaird
Journal: Circulation (1976)

The goal of this study was to develop, on a rational basis, an index of the intrinsic diastolic elastic properties of the left ventricle. A relatively simple analytic model employing a thin-walled spherical geometry coupled with an approximate formulation of a two-dimensional constitutive relation, was used to examine the primary determinants of the pressure-volume relationship of the intact heart. The results permit comparison with other indices of compliance or wall stiffness. The slope of the dP/dV vs P curve was found to be sensitive to the non-linear elastic constant K, but is also sensitive to variations in cardiac muscle volume. VdP/dV was found to be sensitive to pressure. m = d(log P)/d(log V) = (V/P)(dP/dV) is proposed as an index sensitive to K and relatively insensitive to both pressure and initial cardiac geometry. The index is compared with published studies. Using the data of Fester and Samet, mean values of the asymptotic log-log P-V slope, m, evaluated at end-diastole for normal, idiopath...
ATP-dependent closure and reactivation of inward rectifier K+ channels in endothelial cells.
Authors: S POlesen, MBundgaard
Journal: Circulation Research (1993)

This report presents the results of a patch-clamp study examining the role of intracellular ATP in the regulation of endothelial inward rectifier K+ channels. Administration of ATP to the cytosolic surface of inside-out patches reversibly activated the K+ channel within seconds. ATP (1 mM) increased the mean open probability by a factor of 3.5, primarily by increasing the number of openings. Administration of the nonhydrolyzable ATP analogue ATP-gamma-S failed to modulate channel activity. Inhibition of ATP synthesis by administration of cyanide plus iodoacetate resulted in channel closure within 1 to 6 minutes. In experiments in which ATP was coadministered with the metabolic blockers, the channel activity continued unchanged for up to 30 minutes, but when ATP was removed, the activity rapidly decayed. We propose that normal functioning of the inward rectifier K+ channel is ATP dependent. Phosphorylation of the channel molecule is probably essential for maintaining activity.
Advance Care Planning in Older Adults with CKD: Patient, Care Partner, and Clinician Perspectives
Authors: Keren Ladin, Isabel Neckermann, Noah D’Arcangelo, Susan Koch-Weser, John B. Wong, Elisa J. Gordon, Ana Rossi, Dena Rifkin, Tamara Isakova, Daniel E. Weiner
Journal: Journal of the American Society of Nephrology (2021)

Older patients with advanced CKD are at high risk for serious complications and death, yet few discuss advance care planning (ACP) with their kidney clinicians. Examining barriers and facilitators to ACP among such patients might help identify patient-centered opportunities for improvement.In semistructured interviews in March through August 2019 with purposively sampled patients (aged ≥70 years, CKD stages 4-5, nondialysis), care partners, and clinicians at clinics in across the United States, participants described discussions, factors contributing to ACP completion or avoidance, and perceived value of ACP. We used thematic analysis to analyze data.We conducted 68 semistructured interviews with 23 patients, 19 care partners, and 26 clinicians. Only seven of 26 (27%) clinicians routinely discussed ACP. About half of the patients had documented ACP, mostly outside the health care system. We found divergent ACP definitions and perspectives; kidney clinicians largely defined ACP as completion of formal documentation, whereas patients viewed it more holistically, wanting discussions about goals, prognosis, and disease trajectory. Clinicians avoided ACP with patients from minority groups, perceiving cultural or religious barriers. Four themes and subthemes informing variation in decisions to discuss ACP and approaches emerged: (1) role ambiguity and responsibility for ACP, (2) questioning the value of ACP, (3) confronting institutional barriers (time, training, reimbursement, and the electronic medical record, EMR), and (4) consequences of avoiding ACP (disparities in ACP access and overconfidence that patients' wishes are known).Patients, care partners, and clinicians hold discordant views about the responsibility for discussing ACP and the scope for it. This presents critical barriers to the process, leaving ACP insufficiently discussed with older adults with advanced CKD.
Characteristics and Outcomes of Pediatric Patients with t(16;16)-AML: Results of a Case Series By the International BFM Study Group
Authors: Kim Klein, Valerie de Haas, Jonas Abrahamsson, Todd A Alonzo, Brenda Gibson, Christine J Harrison, Henrik Hasle, Betsy A Hirsch, Guy Leverger, Franco Locatelli, Susana C. Raimondi, Jeffrey E Rubnitz, Dirk Reinhardt, Daisuke Tomizawa, Gertjan J.L. Kaspers
Journal: Blood (2017)
A Hidden Treasure Left Behind
Authors: R Mendo, P Barreiro, C Félix, C O’Neill, C Chagas
Journal: Endoscopy (2021)

A 73-year-old man with an early gastric cancer was proposed for treatment by endoscopic submucosal dissection (ESD). The procedure was interrupted due to perforation successfully treated with clips. The patient was then referred to our institution for a new attempt of ESD, where a buried clip absorbed in the submucosa and attached to the muscularis propria was found during submucosal dissection. To the best knowledge of the authors, this is the first described case of ESD where, during the dissection process, a fully absorbed clip in the submucosa was identified, forcing its removal to complete the resection of the lesion
Breast size and cancer.
Authors: T Hirohata, A M Nomura, L N Kolonel
Journal: BMJ (1977)

nauseated and vomited.In addition to these well-known local irritant effects of zinc sulphate on the gastrointestinal tract, con- sideration must be given to potentially toxic side effects of the large and unphysiological concentrations of zinc achieved in human plasma with the recommended zinc sulphate regimen.In the light of these observations we feel that the current recommendations to treat acne vulgaris with 220 mg of zinc sulphate thrice daily is unwarranted owing to the excess quantity of zinc ion absorbed.There is an urgent need to investigate the dose effectiveness of zinc sulphate supplementation not only in patients with acne vulgaris but also in the various other conditions for which zinc has been recommended.This is being done in this department.
Role of nitric oxide in exercise-induced vasodilation of the forearm.
Authors: TEndo, TImaizumi, TTagawa, MShiramoto, SAndo, ATakeshita
Journal: Circulation (1994)

BACKGROUNDWe wished to determine the role of NO in exercise-induced metabolic forearm vasodilation.METHODS AND RESULTSYoung healthy volunteers (n = 11) underwent static handgrip exercise (4 to 5 kg, 3 minutes). Forearm blood flow (FBF) measured by strain plethysmography increased from 4.1 +/- 0.7 mL.min-1.100 mL-1 at rest to 9.8 +/- 1.2 mL.min-1.100 mL-1 immediately after exercise and gradually decreased thereafter. Exercise was repeated after intrabrachial artery infusion of NG-monomethyl-L-arginine (L-NMMA) at 4.0 mumol/min for 5 minutes. L-NMMA did not alter blood pressure and heart rate. L-NMMA decreased FBF at rest to 2.9 +/- 0.4 mL.min-1.100 mL-1 (P < .01), peak FBF immediately after exercise to 7.2 +/- 0.7 mL.min-1.100 mL-1 (P < .01), and FBF during the mid to late phase of metabolic vasodilation (P < .01). Calculated oxygen consumption during peak exercise was comparable before and after L-NMMA. Intra-arterially infused L-arginine (10 mg/min, 5 minutes) reversed the inhibitory effect of L-NMMA. To...
Coronary blood flow in experimental canine left ventricular hypertrophy.
Authors: D DO'Keefe, J IHoffman, RCheitlin, M JO'Neill, J RAllard, EShapkin
Journal: Circulation Research (1978)

To determine whether left ventricular hypertrophy [LVH] altered total and regional coronary blood flow, we inflated a balloon around the ascending aorta of nine dogs; six acute and six sham-operated dogs were controls. After 6 weeks, all dogs were studied with an open chest under anesthesia; the balloons were deflated. There was moderate LVH as shown by increased left ventricular weight and fiber diameter. At rest there were no major differences of coronary flow or resistance per gram of muscle. With maximal coronary vasodilation due to adenosine or carbochrome, mean coronary vascular resistance was 84% higher in LVH than in normal hearts; with isoproterenol, resistance was 54% higher in LVH. These changes were similar in right and left ventricles. Minimal coronary resistance at end diastole also was higher in LVH--64% and 94% for the two sets of vasodilators, respectively. There were no significant differences in capillary or large vessel proportional volumes in LVH and control dogs, but arterial capacit...
Vascular injury augments adrenergic neurotransmission.
Authors: R CCandipan, P THsiun, RPratt, J PCooke
Journal: Circulation (1994)

BACKGROUNDWe have observed persistent desensitization to exogenous norepinephrine after balloon injury. We postulated that this desensitization may be due to a local increase in the release of neuronal norepinephrine.METHODS AND RESULTSNew Zealand White rabbits underwent left iliac artery angioplasty; 4 weeks later, both iliac arteries were harvested. Maximal response to exogenous norepinephrine was reduced in injured compared with noninjured vessels (12.3 +/- 1.0 g versus 10.3 +/- 1.5 g; n = 7, P = .056). By contrast, response to electrical stimulation (to induce neuronal norepinephrine release) was significantly greater in injured tissues (36 +/- 7% versus 14 +/- 3%; values expressed as percent of maximal contraction to exogenous norepinephrine; P = .025). Direct measurement of tissue norepinephrine revealed a threefold increase 4 weeks after injury (1236 +/- 410 versus 466 +/- 97 pg/mg; injured versus noninjured). To determine if desensitization to exogenous norepinephrine was due to a persistent incre...
Mechanical stimulation induces rapid fibroblast proliferation and accelerates the early maturation of human skin substitutes
Authors: Adam Wahlsten, Dominic Rütsche, Monica Nanni, Costanza Giampietro, Thomas Biedermann, Ernst Reichmann, Edoardo Mazza
Journal: Biomaterials (2021)

The clinical treatment of large, full-thickness skin injuries with tissue-engineered autologous dermo–epidermal skin substitutes is an emerging alternative to split-thickness skin grafting. However, their production requires about one month of in vitro cell and tissue culture, which is a significant drawback for the treatment of patients with severe skin defects. With the aim to reduce the production time, we developed a new dynamic bioreactor setup that applies cyclic biaxial tension to collagen hydrogels for skin tissue engineering. By reliably controlling the time history of mechanical loading, the dynamic culturing results in a three-fold increase in collagen hydrogel stiffness and stimulates the embedded fibroblasts to enter the cell cycle. As a result, the number of fibroblasts is increased by 75% compared to under corresponding static culturing. Enhanced fibroblast proliferation promotes expression of dermal extracellular matrix proteins, keratinocyte proliferation, and the early establishment of the epidermis. The time required for early tissue maturation can therefore be reduced by one week. Analysis of the separate effects of cyclic loading, matrix stiffening, and interstitial fluid flow indicates that cyclic deformation is the dominant biophysical factor determining fibroblast proliferation, while tissue stiffening plays a lesser role. Local differences in the direction of deformation (in-plane equibiaxial vs. uniaxial strain) influence fibroblast orientation but not proliferation, nor the resulting tissue properties. Importantly, dynamic culturing does not activate fibroblast differentiation into myofibroblasts. The present work demonstrates that control of mechanobiological cues can be very effective in driving cell response toward a shorter production time for human skin substitutes.
Mechanisms Underlying the Association of Chronic Obstructive Pulmonary Disease With Heart Failure
Authors: Jakub Lagan, Erik B. Schelbert, Josephine H. Naish, Jørgen Vestbo, Christien Fortune, Joshua Bradley, John Belcher, Edward Hearne, Foluwakemi Ogunyemi, Richard Timoney, Daniel Prescott, Hamish D.C. Bain, Tasneem Bangi, Mahvash Zaman, Christopher Wong, Anthony Ashworth, Helen Thorpe, Robin Egdell, Jerome McIntosh, Bruce R. Irwin, David Clark, Graham Devereux, Jennifer K. Quint, Richard Barraclough, Matthias Schmitt, Christopher A. Miller
Journal: JACC. Cardiovascular imaging (2021)

The purposes of this study were to determine why chronic obstructive pulmonary disease (COPD) is associated with heart failure (HF). Specific objectives included whether COPD is associated with myocardial fibrosis, whether myocardial fibrosis is associated with hospitalization for HF and death in COPD, and whether COPD and smoking are associated with myocardial inflammation. COPD is associated with HF independent of shared risk factors. The underlying pathophysiological mechanism is unknown. A prospective, multicenter, longitudinal cohort study of 572 patients undergoing cardiac magnetic resonance (CMR), including 450 patients with COPD and 122 age- and sex-matched patients with a median: 726 days (interquartile range: 492 to 1,160 days) follow-up. Multivariate analysis was used to examine the relationship between COPD and myocardial fibrosis, measured using cardiac magnetic resonance (CMR). Cox regression analysis was used to examine the relationship between myocardial fibrosis and outcomes; the primary endpoint was composite of hospitalizations for HF or all-cause mortality; secondary endpoints included hospitalizations for HF and all-cause mortality. Fifteen patients with COPD, 15 current smokers, and 15 healthy volunteers underwent evaluation for myocardial inflammation, including ultrasmall superparamagnetic particles of iron oxide CMR. COPD was independently associated with myocardial fibrosis (p < 0.001). Myocardial fibrosis was independently associated with the primary outcome (hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.08 to 1.20; p < 0.001), hospitalization for HF (HR: 1.25 [95% CI: 1.14 to 1.36]); p < 0.001), and all-cause mortality. Myocardial fibrosis was associated with outcome measurements more strongly than any other variable. Acute and stable COPD were associated with myocardial inflammation. The associations between COPD, myocardial inflammation and myocardial fibrosis, and the independent prognostic value of myocardial fibrosis elucidate a potential pathophysiological link between COPD and HF.