tbuckley/cabot-search huggingface dataset:
Characterization of a Slowly Inactivating Outward Current in Adult Mouse Ventricular Myocytes
Authors: Jun Zhou, Andreas Jeron, Barry London, Xingqiang Han, Gideon Koren
Journal: Circulation Research (1998)

Abstract —We recently have reported that suppression of the slowly inactivating component of the outward current, I slow , in ventricular myocytes of transgenic mice (long QT mice) overexpressing the N-terminal fragment and S1 segment of Kv1.1 resulted in a significant prolongation of action potential duration and the QT interval. Here we describe the detailed biophysical properties and physiological role of I slow by applying the whole-cell patch-clamp technique at both room temperature and 37°C. This current activates rapidly with time constants ranging from 3.8±0.8 ms at –20 mV to 2.1±0.5 ms at 50 mV at room temperature. The half-activation voltage and slope factor are –12.5±2.6 mV and 7.7±1.0 mV, respectively. The inactivation of this current is slow compared with the fast inactivating component I to , with time constants of ≈100 ms at 37°C. The steady-state inactivation of I slow is not temperature-dependent, with half-inactivation voltages and slope factors of –35.1±1.3 and –5.4±0.4 mV at 37°C, and –37.6±1.8 and –5.8±0.6 mV at room temperature. Double exponentials were required to describe the time-dependent recovery of I slow from steady-state inactivation, with time constants of 233±34 and 3730±702 ms at 37°C, and 830±240 and 8680±2410 ms at room temperature. I slow is highly sensitive to 4-aminopyridine but is insensitive to tetraethylammonium, α-dendrotoxin, and E-4031. Stimulation with action-potential waveforms under voltage-clamp mode revealed that this current plays an important role in the early and middle phases of repolarization of the cardiac action potential. We conclude that the biophysical properties and pharmacological profiles of I slow are similar to those of Kv1.5-encoded currents.
Response to Letter Regarding Article, “B-Type Natriuretic Peptide Signal Peptide Circulates in Human Blood: Evaluation as a Potential Biomarker of Cardiac Ischemia”
Authors: Chris J. Pemberton, A. Mark Richards, Maithri Siriwardena, Vicky A. Cameron, Tim G. Yandle, M. Gary Nicholls, Torsten Kleffmann, Peter Ruygrok
Journal: Circulation (2011)
Novel Role of gp91 <sup>phox</sup> -Containing NAD(P)H Oxidase in Vascular Endothelial Growth Factor–Induced Signaling and Angiogenesis
Authors: Masuko Ushio-Fukai, Yan Tang, Tohru Fukai, Sergey I. Dikalov, Yuxian Ma, Mitsuaki Fujimoto, Mark T. Quinn, Patrick J. Pagano, Chad Johnson, R. Wayne Alexander
Journal: Circulation Research (2002)

Vascular endothelial growth factor (VEGF) induces angiogenesis by stimulating endothelial cell proliferation and migration, primarily through the receptor tyrosine kinase VEGF receptor2 (Flk1/KDR). Reactive oxygen species (ROS) derived from NAD(P)H oxidase are critically important in many aspects of vascular cell regulation, and both the small GTPase Rac1 and gp91 phox are critical components of the endothelial NAD(P)H oxidase complex. A role of NAD(P)H oxidase in VEGF-induced angiogenesis, however, has not been defined. In the present study, electron spin resonance spectroscopy is utilized to demonstrate that VEGF stimulates O 2 ·− production, which is inhibited by the NAD(P)H oxidase inhibitor, diphenylene iodonium, as well as by overexpression of dominant-negative Rac1 (N17Rac1) and transfection of gp91 phox antisense oligonucleotides in human umbilical vein endothelial cells (ECs). Antioxidants, including N -acetylcysteine (NAC), various NAD(P)H oxidase inhibitors, and N17Rac1 significantly attenuate not only VEGF-induced KDR tyrosine phosphorylation but also proliferation and migration of ECs. Importantly, these effects of VEGF are dramatically inhibited in cells transfected with gp91 phox antisense oligonucleotides. By contrast, ROS are not involved in mediating these effects of sphingosine 1-phosphate (S1P) on ECs. Sponge implant assays demonstrate that VEGF-, but not S1P-, induced angiogenesis is significantly reduced in wild-type mice treated with NAC and in gp91 phox−/− mice, suggesting that ROS derived from gp91 phox -containing NAD(P)H oxidase play an important role in angiogenesis in vivo. These studies indicate that VEGF-induced endothelial cell signaling and angiogenesis is tightly controlled by the reduction/oxidation environment at the level of VEGF receptor and provide novel insights into the NAD(P)H oxidase as a potential therapeutic target for angiogenesis-dependent diseases.
Optical superresolution and visual hyperacuity
Authors: Gerald Westheimer
Journal: Progress in Retinal and Eye Research (2012)

Classically, diffraction theory sets a boundary for the resolving capacity of optical instruments. Yet some visual thresholds have values much better than the traditional resolution limit. Recent developments in superresolution, an area of optical physics and engineering with claims of transcending the stated resolution limits of optical instruments, are reviewed and their possible relevance to visual spatial processing and to the exploration of the eye's structure are assessed. In optical or diffractive superresolution the transmitted spatial-frequency band is not so much extended as either multiplexed with or displaced into regions that are usually beyond reach, with no overall gain in information transfer because prior knowledge is used to make inferences of possible object structure from the image. The Uncertainty Principle for photon position and momentum is never disobeyed. The study of the neural substrate of visual hyperacuity does, however, overlap that of "geometrical superresolution," in which techniques are used for transcending limits imposed by the receptor lattice in analyzing fine image structure.
Radioactive 133-Xenon Gas-Filled Balloon to Prevent Restenosis
Authors: Marc Apple, Ron Waksman, Rosanna C. Chan, Yoram Vodovotz, Jana Fournadjiev, Bill G. Bass
Journal: Circulation (2002)

Ionizing radiation administered intraluminally via catheter-based systems using solid beta and gamma sources or liquid-filled balloons has shown reduction in the neointima formation after injury in the porcine model. We propose a novel system that uses a 133-Xenon (133Xe) radioactive gas-filled balloon catheter system.Overstretch balloon injury was performed in the coronary arteries of 33 domestic pigs. A novel 133Xe radioactive gas-filled balloon (3.5/45 mm) was positioned to overlap the injured segment with margins. After vacuum was obtained in the balloon catheter, approximately 2.5 cc of 133Xe gas was injected to fill the balloon. Doses of 0, 7.5, 15, and 30 Gy were delivered to a distance of 0.25 mm from the balloon surface. The dwell time ranged from 1.0 to 4.0 minutes, depending on the dose. Localization of 133Xe in the balloon was verified by a gamma camera. The average activity in a 3.5/45-mm balloon was measured at 67.7+/-12.1 mCi, and the total diffusion loss of the injected dose was 0.26% per minute of the injected dose. Bedside radiation exposure measured between 2 and 6 mR/h, and the shallow dose equivalent was calculated as 0.037 mrem per treatment. Histomorphometric analysis at 2 weeks showed inhibition of the intimal area (intimal area corrected for medial fracture length [IA/FL]) in the irradiated segments of 0.26+/-0.08 with 30 Gy, 0.07+/-0.24 with 15 Gy, and 0.12+/-0.89 with 7.5 Gy versus 0.76+/-0.08 with control P<0.001.133Xe gas-filled balloon is feasible and effective in the reduction of neointima formation in the porcine model and safe for use in coronary arteries.
Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA)
Authors: Maxime Dougados, Martin Soubrier, Anna Antunez, Peter Balint, Alejandro Balsa, Maya H Buch, Gustavo Casado, Jacqueline Detert, Bassel El-zorkany, Paul Emery, Najia Hajjaj-Hassouni, Masayoshi Harigai, Shue-Fen Luo, Reka Kurucz, Gabriel Maciel, Emilio Martin Mola, Carlo Maurizio Montecucco, Iain McInnes, Helga Radner, Josef S Smolen, Yeong-Wook Song, Harald Erwin Vonkeman, Kevin Winthrop, Jonathan Kay
Journal: Annals of the Rheumatic Diseases (2013)

Lafora disease (LD) can be diagnosed by skin biopsy, but this approach has both false negatives and false positives. Biopsies of other organs can also be diagnostic but are more invasive. Genetic diagnosis is also possible but can be inconclusive, for example, in patients with only one heterozygous <i>EPM2A</i> mutation and patients with apparently homozygous <i>EPM2B</i> mutations where one parent is not a carrier of the mutation. We sought to identify occult mutations and clarify the genotypes and confirm the diagnosis of LD in patients with apparent nonrecessive disease inheritance. We used single nucleotide polymorphism, quantitative PCR, and fluorescent in situ hybridization analyses. We identified large <i>EPM2A</i> and <i>EPM2B</i> deletions undetectable by PCR in the heterozygous state and describe simple methods for their routine detection. We report a coding sequence change in several patients and describe why the pathogenic role of this change remains unclear. We confirm that adult-onset LD is due to <i>EPM2B</i> mutations. Finally, we report major intrafamilial heterogeneity in age at onset in LD.
The 14-3-3σ Tumor Suppressor Has Multiple Functions in ErbB2-Induced Breast Cancer
Authors: Nancy E. Hynes, Tatiana Smirnova
Journal: Cancer Discovery (2012)

Abstract Ling and colleagues demonstrated that loss of the conditional 14-3-3σ allele results in accelerated HER2/ERBB2-driven mammary tumorigenesis and metastasis. This study underscores the role of 14-3-3σ as a potent tumor suppressor in ERBB2-driven tumor initiation and progression. Cancer Discovery; 2(1); 19–22. ©2012 AACR. Commentary on Ling et al., p. 68.
Altered White Matter Integrity in the Corpus Callosum in Fibromyalgia Patients Identified by Tract‐Based Spatial Statistical Analysis
Authors: Dajung J. Kim, Manyoel Lim, June Sic Kim, Kyeong Min Son, Hyun Ah Kim, Chun Kee Chung
Journal: Arthritis & Rheumatology (2014)

Although recent imaging studies of fibromyalgia (FM) have converged on a dysfunction of central pain processing as the primary pathophysiologic cause of the disorder, microstructural changes of the white matter (WM) suggestive of abnormalities in the anatomic connectivity of the brain have not been extensively examined. The aim of this study was to investigate WM integrity and its possible relationship to pain symptoms in women with FM.Nineteen FM patients and 21 age-, sex-, and education-matched healthy control subjects were included in the study and underwent diffusion-weighted imaging. Group differences in WM integrity, which were assessed via fractional anisotropy (FA), was investigated by applying tract-based spatial statistics.As compared with the healthy control group, the FM group showed a single cluster with lower FA in the left body of the corpus callosum, which was found to be connected to the bilateral sensorimotor cortices (P < 0.05, corrected for multiple comparisons). Furthermore, FA values in the cluster were negatively associated with sensory pain, as measured by the Short-Form McGill Pain Questionnaire, as well as with the relative magnitude of sensory pain versus affective pain (calculated by dividing the sensory score by the affective score).Findings of the current study demonstrated that patients with FM had disrupted WM microstructure in the body of the corpus callosum, which was associated with clinical pain intensity. Our results suggest that abnormal interhemispheric transfer might contribute to the heightened pain perception. Our findings further strengthen the hypothesis of centrally augmented pain processing in patients with FM.
Camostate (FOY-305) improves the therapeutic effect of peritoneal lavage on taurocholate induced pancreatitis.
Authors: U Leonhardt, F Seidensticker, M Fussek, F Stockmann, W Creutzfeldt
Journal: Gut (1990)

The effect of peritoneal lavage with the addition of camostate to the lavage fluid on the outcome of taurocholate pancreatitis in rats was studied. Camostate is a low molecular weight protease inhibitor which has been developed recently. Peritoneal lavage was performed for 12 hours and camostate was added to the lavage fluid in five concentrations. At 0.1 mg/ml the survival rate increased significantly (11 of 20 v controls 4 of 20, p less than 0.05); the maximal effect was observed at 0.2 mg/ml, and no effect was seen at 0.01 and 0.05 mg/ml. Adverse effects occurred at 0.5 mg/ml. The addition of 0.1 mg/ml camostate significantly reduced the acidosis in arterial blood: mean (SD) pH 7.30 (0.035) v controls 7.23 (0.054) (n = 9, p less than 0.01) and arterial base excess: -15.4 (1.26) mmol/l v controls: -17.4 (2.51) mmol/l (n = 9, p less than 0.05). There was no difference, however, in plasma amylase activity and in the histological degree of specific tissue damage to the pancreas. A combination of intravenous camostate and lavage with the addition of camostate to the lavage fluid yielded a significantly improved survival compared with treatment with intravenous camostate alone (10 out of 16 animals v intravenous camostate alone, two out of 16, p greater than 0.01). We conclude that lavage with camostate significantly improves the prognosis of severe necrotising pancreatitis in rats.
Managed Care Market Penetration, Spillover Effects, and the Quality of Cancer Care
Authors: J. Lipscomb
Journal: JNCI Journal of the National Cancer Institute (2005)

Proponents of managed care extol its potential to control costs and improve quality through an emphasis on prevention, screening, and treatment that is evidence based, coordinated, and prudent in the use of public and private dollars. The focus is on promoting wellness, a win – win situation from the standpoint of both health outcomes and costs. Critics counter that managed care organizations — budget constrained and unable to fully capture the potential cost savings from aggressive prevention and screening because of inevitable fl uctuations in plan enrollment — actually have substantial incentives to limit access to care. Specifi cally, managed care organizations seek to control costs by modulating the volume and mix of services through a combination of provider incentives and restraints, limits on investments in technology and infrastructure, and a maze of price and nonprice barriers imposed on enrollees. The complex truth of the matter surely lies somewhere between these two stylized characterizations. This becomes quickly evident from any survey of the large, empirically rich health services research literature in this general area over the past three decades. At the moment, innovative research to better understand the structure, performance, and overall impact of managed health care is more pressing and more challenging than ever before. It is more pressing because, at least in the United States, private employers and governments at all levels will continue to rely on, and may accelerate the adoption of, managed care as a vehicle for controlling costs. It is more challenging because managed care has evolved over time from the comparatively monolithic, prepaid group practice – based health maintenance organization (HMO) model to a multiplicity of organizational forms, including several variants of the HMO, preferred provider organizations (PPOs), point-of-service (POS) plans, and various hybrid
Deoxycholate depresses small-intestinal enzyme activity.
Authors: M Gracey, M Houghton, J Thomas
Journal: Gut (1975)

Feeding sodium deoxycholate orally to rats for four days caused depression of the activity of the small intestinal enzymes lactase, sucrase, maltase, alkaline phosphatase, and N-acetyl-beta-glucosaminidase. The first four are brush border enzymes, the last a lysosomal enzyme. Alkaline phosphatase activity recovered very rapidly and rebounded to above the normal level within 24 hours. The activity of the three disaccharidases returned to normal within seven days while no recovery was observed within 96 hours of the activity of the lysosomal enzyme, N-acetyl-beta-glucosaminidase, after removing the bile salt from the diet.
Enhanced Chromatid Damage in Blood Lymphocytes After G 2 Phase X Irradiation, a Marker of the Ataxia-Telangiectasia Gene
Authors: Katherine K. Sanford, Ram Parshad, Floyd M. Price, Gary M. Jones, Robert E. Tarone, Lindsay Eierman, Paula Hale, Thomas A. Waldmann
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Enhanced Chromatid Damage in Blood Lymphocytes After G 2 Phase X Irradiation, a Marker of the Ataxia-Telangiectasia Gene Get access Katherine K. Sanford, Katherine K. Sanford Search for other works by this author on: Oxford Academic PubMed Google Scholar Ram Parshad, Ram Parshad Search for other works by this author on: Oxford Academic PubMed Google Scholar Floyd M. Price, Floyd M. Price Search for other works by this author on: Oxford Academic PubMed Google Scholar Gary M. Jones, Gary M. Jones Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert E. Tarone, Robert E. Tarone Search for other works by this author on: Oxford Academic PubMed Google Scholar Lindsay Eierman, Lindsay Eierman Search for other works by this author on: Oxford Academic PubMed Google Scholar Paula Hale, Paula Hale Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas A. Waldmann Thomas A. Waldmann Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 12, 20 June 1990, Pages 1050–1054, https://doi.org/10.1093/jnci/82.12.1050 Published: 20 June 1990 Article history Received: 07 March 1990 Revision received: 02 April 1990 Accepted: 06 April 1990 Published: 20 June 1990
Ultra-Low-Dose Chest Computer Tomography Screening of an Asbestos-exposed Population in Western Australia
Authors: Fraser J. H. Brims, Conor P. Murray, Nick de Klerk, Helman Alfonso, Alison Reid, David Manners, Patrick M. Wong, Joelin Teh, Nola Olsen, Robin Mina, A. W. Musk
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
RECIST and Choi criteria for response assessment (RA) in patients with inoperable and metastatic gastrointestinal stromal tumours (GISTs) on imatinib mesylate. Cambridge GIST study group experience
Authors: V. R. Bulusu, C. R. Jephcott, S. Fawcett, N. Cook, H. Hatcher, P. Moyle, N. Carroll, H. Earl, V. Save, R. Hardwick
Journal: Journal of Clinical Oncology (2007)

10019 Background: Imatinib Mesylate (IM) induces an overall response rate of 84% in patients (pts) with metastatic GISTs. Standard RA is by RECIST criteria. This may underestimate the true benefit of IM in such pts. Choi et al observed ↓ in size (10%) and or density (D) (15%) correlated well with disease specific survival. We report our experience using both RECIST and Choi criteria for RA in GIST pts on IM. Methods: Between 2003 and 06, 24 pts with metastatic or inoperable GISTs were treated with IM. 50 lesions (Liver 20, Omentum 21, Primary 9) were identified at presentation on contrast CT (Siemens multi slice CT, IV Niopam, GE PACS system). 3 monthly CT was used for RA until tumour progression (PD) or death. Parameters recorded were: 1.Largest dimension 2. Lesion density (Mean Hounsfield units, HFU) 3.New lesions 4.Any new features. RECIST and Choi criteria were both applied for RA. Results: N=50. At 3 months (m) only 16% of the lesions achieved partial response (PR) by RECIST and 24% increased in size by a mean of 22.5% (Range 3–150%). RA as measured by Choi criteria revealed 88% of lesions had either a 10% ↓ in size or a 15% ↓ in D at 3 m. Mean ↓ in D was 29% (95% CI 24.6–33.4). At 18 m 50% of the lesions achieved PR and 20% had PD by RECIST criteria, and with Choi criteria 68% RR was recorded. Calcification, haemorrhage and perforation within the lesions spuriously altered the mean D value in 15% of the lesions which made assessment by Choi criteria difficult. In 5 pts new hepatic cystic lesions (range 2–22) appeared with a mean D of 16 HF. None were detected in extra-hepatic sites. 4 pts showed new calcifications within lesions 3–18 m on IM. Enhancing nodules within lesions were seen in 4 pts predating clinical PD by 6–18 m. Conclusions: Choi criteria were found to be reproducible in our pts. RRs at 3 months using Choi criteria (88%) were far greater than by RECIST criteria (16%). RRs were more similar at 18 m (68% Choi vs 50% RECIST).Using density for RA can become unreliable in the presence of perforation, calcification and haemorrhage. These criteria should be evaluated by a radiologist experienced in assessing the response to IM in GISTs with awareness of their limitations. No significant financial relationships to disclose.
SEROLOGICAL STUDIES ON AZOPROTEINS
Authors: E. Landsteiner, J. van der Scheer
Journal: The Journal of Experimental Medicine (1934)

A study was made of the specificity of artificial compound-antigens containing aliphatic chains. Striking specificity was exhibited in the reactions of compounds with short chains containing a carboxyl group; for instance succinic acid could be differentiated from malonic or glutaric acid which contain one fewer and one more carbon atom respectively. With the substances containing longer chains, reactions were observed which, although specific to a certain extent, appear to depend mainly on the general physicochemical properties of long aliphatic chains. With a limited number of substances the influence of substituents -halogen, OH, NH(2)-on the serological specificity was investigated. By means of inhibition reactions it was possible to demonstrate the serological specificity of cis-trans isomers such as maleic and fumaric acid.
Intra-coronary administration of ?-arginine aggravates myocardial stunning through production of peroxynitrite in dogs
Authors: E Mori
Journal: Cardiovascular Research (1998)

Objective: The aim of this study was to investigate how the enhanced nitric oxide (NO) production by intra-coronary infusion of l-arginine acts in myocardial stunning in dogs by focusing on the involvement of peroxynitrite, a reaction product of NO and superoxide anion. Methods and Results: Dogs were divided into six groups; a control non-treated group (CON, n=9), and NG-nitro l-arginine methyl ester (l-NAME, n=6), 1 mM l-arginine (l-ARG, n=8), d-arginine (d-ARG, n=6), l-arginine plus superoxide dismutase (l-ARG+SOD, n=6), and SOD alone (SOD, n=6) treated groups. l-NAME, or l- or d-arginine was continuously infused into the left anterior descending coronary artery (LAD) starting just prior to reperfusion, whereas SOD was intravenously injected before occlusion. During 120 min of reperfusion after 15 min occlusion of LAD, myocardial contractile function in the ischemic region gradually recovered and reached approximately 70% of the preischemic level in CON, d-ARG and SOD, but it remained dyskinetic (−46%) in l-ARG. On the other hand, it was improved in l-NAME (90%). Tissue malondialdehyde was elevated (p<0.005) after reperfusion, and myocardial NO metabolites measured by an intratissue-microdialyzer increased (approximately 150%, p<0.05) in the ischemic region during reperfusion in l-ARG but not in the CON, l-NAME, d-ARG or SOD groups. In the l-ARG+SOD group, l-arginine-induced contractile dysfunction and elevation of malondialdehyde were prevented, but the increase in NO metabolites remained. These results suggest that l-arginine aggravated myocardial stunning through oxidative stress and the cytotoxicity was caused by NO derivatives but not by NO itself. The formation of nitrotyrosine, a footprint of peroxynitrite, was immunohistochemically confirmed in the ischemic region of l-ARG. Conclusions: Our results demonstrate for the first time in vivo that NO has a detrimental role in myocardial stunning through the production of peroxynitrite.