tbuckley/cabot-search huggingface dataset:
Psychogenic facial pain: presentation and treatment.
Authors: C Feinmann, M Harris, R Cawley
Journal: BMJ (1984)

Ninety three patients took part in a two centre double blind controlled clinical trial designed to assess the efficacy of dothiepin (Prothiaden) as compared with placebo and a soft biteguard in the treatment of psychogenic facial pain. The results showed the superiority of dothiepin over placebo in achieving pain relief; 71% of patients were pain free in the dothiepin group at nine weeks compared with 47% in the placebo group. The biteguard conferred no benefit and compliance in its use was poor. Out of 84 patients followed up for 12 months, 68 (81%) became pain free. An adverse life event before development of pain, minimal previous surgical treatment, and freedom from pain at nine weeks were strong prognostic indicators for successful treatment. These results are clear evidence of the efficacy of dothiepin in psychogenic facial pain, though the drug may be needed for up to a year.
Targeting the B-Cell Lymphoma/Leukemia 2 Family in Cancer
Authors: Matthew S. Davids, Anthony Letai
Journal: Journal of Clinical Oncology (2012)

The B-cell lymphoma/leukemia 2 (BCL-2) family of proteins has attracted the attention of cancer biologists since the cloning of BCL-2 more than 25 years ago. In the intervening decades, the way the BCL-2 family controls commitment to programmed cell death has been greatly elucidated. Several drugs directed at inhibiting BCL-2 and related antiapoptotic proteins have been tested clinically, with some showing considerable promise, particularly in lymphoid malignancies. A better understanding of the BCL-2 family has also provided insight into how conventional chemotherapy selectively kills cancer cells and why some cancers are more chemosensitive than others. Further exploitation of our understanding of the BCL-2 family promises to offer improved predictive biomarkers for oncologists and improved therapies for patients with cancer.
The use of left ventricular end-ejection pressure and peak pressure in the estimation of the end-systolic pressure-volume relationship.
Authors: A Kono, W L Maughan, K Sunagawa, K Hamilton, K Sagawa, M L Weisfeldt
Journal: Circulation (1984)

The end-systolic pressure-volume relationship (ESPVR) as derived from left ventricular pressure-volume loops has gained increasing acceptance as an index of ventricular contractile function. In animal experiments the ESPVR has been defined as a line connecting the upper left corners of several differently loaded pressure-volume (P-V) loops with a slope parameter Ees and a volume axis intercept parameter Vo. In the clinical setting, several variants of the ESPVR have been determined with use of peak left ventricular pressure, end-ejection pressure, and end-ejection volume. The maximum P-V ratio has also frequently been measured. We attempted to determine which of these alternatives resulted in good approximations of the reference ESPVR in eight isolated canine ventricles that ejected into a simulated arterial impedance system with resistance, compliance, and characteristic impedance. We determined various versions of the ESPVR from the same set of beats quickly obtained with little change in inotropic background. To vary ventricular pressure wave forms, each of the arterial impedance parameters was independently controlled at 50%, 100%, and 200% of normal. Against each of the nine combinations of the impedance parameters four P-V loops were obtained under four preloads and from each of the sets of four P-V loops, the reference ESPVR, linear regression of the peak pressure on end-ejection volume (ESPVRPP-EEV), and linear regression of end-ejection pressure on end-ejection volume (ESPVREEPV) were determined. In addition, the maximum P-V ratio (MPVR) was calculated for each P-V loop.(ABSTRACT TRUNCATED AT 250 WORDS)
Unusual amino acid heterogeneity within the HCV-1b NS5a region for patients with hepatocellular carcinoma
Authors: M. Giménez-Barcons, X. Forns, Y. Suárez, A. Sánchez-Fueyo, A. Ampurdanès, J.M. Barrera, J.M. Llovet, J. Bruix, J. Rodés, J.M. Sánchez-Tapias, J.C. Sáiz
Journal: Journal of Hepatology (2000)
Précis of <i>Neural organization: Structure, function, and dynamics</i>
Authors: Michael A. Arbib, Péter Érdi
Journal: Behavioral and Brain Sciences (2000)

Neural organization: Structure, function, and dynamics shows how theory and experiment can supplement each other in an integrated, evolving account of the brain's structure, function, and dynamics. (1) Structure: Studies of brain function and dynamics build on and contribute to an understanding of many brain regions, the neural circuits that constitute them, and their spatial relations. We emphasize Szentágothai's modular architectonics principle, but also stress the importance of the microcomplexes of cerebellar circuitry and the lamellae of hippocampus. (2) Function: Control of eye movements, reaching and grasping, cognitive maps, and the roles of vision receive a functional decomposition in terms of schemas. Hypotheses as to how each schema is implemented through the interaction of specific brain regions provide the basis for modeling the overall function by neural networks constrained by neural data. Synthetic PET integrates modeling of primate circuitry with data from human brain imaging. (3) Dynamics: Dynamic system theory analyzes spatiotemporal neural phenomena, such as oscillatory and chaotic activity in both single neurons and (often synchronized) neural networks, the self-organizing development and plasticity of ordered neural structures, and learning and memory phenomena associated with synaptic modification. Rhythm generation involves multiple levels of analysis, from intrinsic cellular processes to loops involving multiple brain regions. A variety of rhythms are related to memory functions. The Précis presents a multifaceted case study of the hippocampus. We conclude with the claim that language and other cognitive processes can be fruitfully studied within the framework of neural organization that the authors have charted with John Szentágothai.
Oxidative Stress Activates Endothelial Innate Immunity via Sterol Regulatory Element Binding Protein 2 (SREBP2) Transactivation of MicroRNA-92a
Authors: Zhen Chen, Liang Wen, Marcy Martin, Chien-Yi Hsu, Longhou Fang, Feng-Mao Lin, Ting-Yang Lin, McKenna J. Geary, Greg G. Geary, Yongli Zhao, David A. Johnson, Jaw-Wen Chen, Shing-Jong Lin, Shu Chien, Hsien-Da Huang, Yury I. Miller, Po-Hsun Huang, John Y-J. Shyy
Journal: Circulation (2014)

Oxidative stress activates endothelial innate immunity and disrupts endothelial functions, including endothelial nitric oxide synthase-derived nitric oxide bioavailability. Here, we postulated that oxidative stress induces sterol regulatory element-binding protein 2 (SREBP2) and microRNA-92a (miR-92a), which in turn activate endothelial innate immune response, leading to dysfunctional endothelium.Using cultured endothelial cells challenged by diverse oxidative stresses, hypercholesterolemic zebrafish, and angiotensin II-infused or aged mice, we demonstrated that SREBP2 transactivation of microRNA-92a (miR-92a) is oxidative stress inducible. The SREBP2-induced miR-92a targets key molecules in endothelial homeostasis, including sirtuin 1, Krüppel-like factor 2, and Krüppel-like factor 4, leading to NOD-like receptor family pyrin domain-containing 3 inflammasome activation and endothelial nitric oxide synthase inhibition. In endothelial cell-specific SREBP2 transgenic mice, locked nucleic acid-modified antisense miR-92a attenuates inflammasome, improves vasodilation, and ameliorates angiotensin II-induced and aging-related atherogenesis. In patients with coronary artery disease, the level of circulating miR-92a is inversely correlated with endothelial cell-dependent, flow-mediated vasodilation and is positively correlated with serum level of interleukin-1β.Our findings suggest that SREBP2-miR-92a-inflammasome exacerbates endothelial dysfunction during oxidative stress. Identification of this mechanism may help in the diagnosis or treatment of disorders associated with oxidative stress, innate immune activation, and endothelial dysfunction.
Vorinostat and Sorafenib Increase CD95 Activation in Gastrointestinal Tumor Cells through a Ca2+-<i>De novo</i> Ceramide-PP2A-Reactive Oxygen Species–Dependent Signaling Pathway
Authors: Margaret A. Park, Clint Mitchell, Guo Zhang, Adly Yacoub, Jeremy Allegood, Dieter Häussinger, Roland Reinehr, Andrew Larner, Sarah Spiegel, Paul B. Fisher, Christina Voelkel-Johnson, Besim Ogretmen, Steven Grant, Paul Dent
Journal: Cancer Research (2010)

The targeted therapeutics sorafenib and vorinostat interact in a synergistic fashion to kill carcinoma cells by activating CD95, and this drug combination is entering phase I evaluation. In this study, we determined how CD95 is activated by treatment with this drug combination. Low doses of sorafenib and vorinostat, but not the individual drugs, rapidly increased reactive oxygen species (ROS), Ca(2+), and ceramide levels in gastrointestinal tumor cells. The production of ROS was reduced in Rho zero cells. Quenching ROS blocked drug-induced CD95 surface localization and apoptosis. ROS generation, CD95 activation, and cell killing was also blocked by quenching of induced Ca(2+) levels or by inhibition of PP2A. Inhibition of acidic sphingomyelinase or de novo ceramide generation blocked the induction of ROS; however, combined inhibition of both acidic sphingomyelinase and de novo ceramide generation was required to block the induction of Ca(2+). Quenching of ROS did not affect drug-induced ceramide/dihydro-ceramide levels, whereas quenching of Ca(2+) reduced the ceramide increase. Sorafenib and vorinostat treatment radiosensitized liver and pancreatic cancer cells, an effect that was suppressed by quenching ROS or knockdown of LASS6. Further, sorafenib and vorinostat treatment suppressed the growth of pancreatic tumors in vivo. Our findings show that induction of cytosolic Ca(2+) by sorafenib and vorinostat is a primary event that elevates dihydroceramide levels, each essential steps in ROS generation that promotes CD95 activation.
Heart rates during competitive orienteering.
Authors: S R Bird, R Bailey, J Lewis
Journal: British Journal of Sports Medicine (1993)

This study investigated the heart rate profiles of 16 experienced, competitive orienteers (aged 15-62 years) during three competitive events. Each competitor was assessed over three different types of course which were classified as: fast run (FR), slow run (SR) and highly physical (HP). The results showed that all subjects recorded heart rates that were between 140 and 180 beats min-1 for the majority of each event (irrespective of age or course type). The heart rate data indicated that the activity was largely aerobic but varied in intensity, with phases of strenuous anaerobic work. The type of course was shown significantly (analysis of variance; P < 0.001) to affect the mean heart rate attained by each orienteer (FR = 160, HP = 158, SR = 150 beats min-1), with courses that required more technical skill and hence slower running producing lower mean heart rates; although the general physical demands were similar for all courses. The older orienteers (> 45 years) recorded heart rate profiles that were similar to those of the young orienteers with no correlation being found between age and mean heart rate while exercising.
Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial
Authors: Hagop Kantarjian, Ricardo Pasquini, Nelson Hamerschlak, Philippe Rousselot, Jerzy Holowiecki, Saengsuree Jootar, Tadeusz Robak, Nina Khoroshko, Tamas Masszi, Aleksander Skotnicki, Andrzej Hellmann, Andrey Zaritsky, Anatoly Golenkov, Jerald Radich, Timothy Hughes, Athena Countouriotis, Neil Shah
Journal: Blood (2007)
ANGIOTONIN-ACTIVATOR, RENIN- AND ANGIOTONIN-INHIBITOR, AND THE MECHANISM OF ANGIOTONIN TACHYPHYLAXIS IN NORMAL, HYPERTENSIVE, AND NEPHRECTOMIZED ANIMALS
Authors: Irvine H. Page, O. M. Helmer
Journal: The Journal of Experimental Medicine (1940)

1. Angiotonin does not exert its vasoconstrictor effect in the absence of a substance contained in red blood cells and serum which we have called "angiotonin-activator." A fraction has been separated from blood in which angiotonin-activator is concentrated. It contains little or no reninactivator. 2. Repeated intravenous injections of angiotonin into animals causes the pressor response gradually to lessen and finally to disappear (the phenomenon of tachyphylaxis), but much more slowly than when renin is injected. When the response to angiotonin is abolished, renin also fails to act. Large doses of renin reduce and finally abolish the responsiveness to angiotonin. Exhaustion of renin-activator in the blood abolishes the response to renin without abolishing the response to angiotonin. 3. Blood from animals made tachyphylactic by infusion of angiotonin contains greatly reduced amounts of angiotonin-activator. An inhibitor also appears in the blood. 4. Bilateral nephrectomy prolongs and greatly enhances the rise of arterial pressure following injection of angiotonin and renin. The enhancement reaches a maximum in from 24 to 30 hours after operation. Blood from these animals exhibits greatly increased ability to activate angiotonin and renin when tested in isolated perfused organs. Large amounts of angiotonin are required to reduce the amount of activator in their blood. Renin-activator is simultaneously but little affected. 5. Tranfusion of blood from an animal made tachyphylactic to angiotonin into a nephrectomized dog reduces the response of the latter to angiotonin. Angiotonin when added to the blood of the recipient of the transfusion and perfused through a rabbit's ear also exhibits greatly reduced vasoconstrictor action. 6. Transfusion of normal blood in large amounts into nephrectomized or hypertensive dogs reduces the recipient's response to renin. If renintachyphylaxis is established in the donor, transfusion abolishes the response to renin in the recipient. The blood from such animals exhibits greatly reduced vasoconstrictor properties when perfused through an isolated organ with renin or angiotonin. 7. Renin-tachyphylactic or normals dog's blood does not reduce arterial pressure elevated by a single injection of renin into nephrectomized dogs. 8. Nephrectomized dogs exhibit the greatest pressor response to infusion of angiotonin and renin, normal animals the least, and hypertensive animals about midway between.
Evi-1 is a transcriptional target of mixed-lineage leukemia oncoproteins in hematopoietic stem cells
Authors: Shunya Arai, Akihide Yoshimi, Munetake Shimabe, Motoshi Ichikawa, Masahiro Nakagawa, Yoichi Imai, Susumu Goyama, Mineo Kurokawa
Journal: Blood (2010)
Influence of antiretroviral therapy on immunogenicity of simultaneous vaccinations against influenza, pneumococcal disease and hepatitis A and B in human immunodeficiency virus positive individuals
Authors: S. Horster, R.P. Laubender, L. Lehmeyer, D.P. Ankerst, J. Eberle, R. Reinert, M. Imöhl, M. van der Linden, B. Schweiger, J.R. Bogner
Journal: Journal of Infection (2010)
Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia
Authors: Sebastian Schwind, Guido Marcucci, Jessica Kohlschmidt, Michael D. Radmacher, Krzysztof Mrózek, Kati Maharry, Heiko Becker, Klaus H. Metzeler, Susan P. Whitman, Yue-Zhong Wu, Bayard L. Powell, Maria R. Baer, Jonathan E. Kolitz, Andrew J. Carroll, Richard A. Larson, Michael A. Caligiuri, Clara D. Bloomfield
Journal: Blood (2011)
ATP hydrolysis cycles and mechanism inP-glycoprotein and CFTR
Authors: Alan E. Senior, David C. Gadsby
Journal: Seminars in Cancer Biology (1997)

P-glycoprotein and CFTR are prominent members of the ABC Transporter family. Both use ATP, the former to drive extrusion of drugs from cells and confer multidrug-resistance, the latter to drive opening and closing of anion channels. We compare current working models of catalytic cycle and mechanism of the two proteins. In Pgp the NBDs appear functionally equivalent, in CFTR they appear functionally distinct. In both proteins, ATP hydrolysis occurs in both NBDs, and it is proposed that the two NBDs alternate in catalysis. Other differences and similarities are noted, fostering ideas for future developments.
Fc gamma receptor III on human neutrophils. Allelic variants have functionally distinct capacities.
Authors: J E Salmon, J C Edberg, R P Kimberly
Journal: Journal of Clinical Investigation (1990)

As a model system to explore the functional consequences of structural variants of human Fc gamma receptors (Fc gamma R), we have investigated Fc gamma R-mediated phagocytosis in relation to the NA1-NA2 polymorphism of Fc gamma RIII (CD16) on neutrophils (Fc gamma RIIIPMN). The neutrophil-specific NA antigen system is a biallelic polymorphism with codominant expression demonstrating a gene dose effect with the anti-NA1 MAb CLB-gran 11 in a large donor population. To explore the impact of this allelic variation of Fc gamma RIIIPMN on phagocytosis, we used two Fc gamma RIII-dependent probes, IgG-sensitized erythrocytes (EA) and concanavalin. A-treated erythrocytes (E-ConA). Comparison of Fc gamma R-mediated phagocytosis by PMN from NA1 subjects and from NA2 subjects showed lower levels of phagocytosis of both probes by the NA2 individuals. The difference was most pronounced with lightly opsonized EA: at the lowest level of sensitization the phagocytic index was 72% lower for NA2 donors, whereas at the highest level of sensitization it was 21% lower (P less than 0.003). Blockade of Fc gamma RII with MAb IV.3 Fab amplified by threefold the difference between NA1 and NA2 donors. NA1 and NA2 individuals had identical phagocytic capacities for the non-Fc gamma RIII probes, serum-treated and heat-treated zymosan. These individuals did not show differential quantitative cell surface expression of Fc gamma RIIIPMN measured by a panel of anti-CD16 MAb (3G8, CLB FcR-gran 1, VEP13, BW209/2) and by Scatchard analysis of 125I-IgG dimer binding. The difference in Fc gamma R-mediated phagocytosis was not explicable on the basis of differential collaboration of Fc gamma RIIIPMN alleles with Fc gamma RII, since (a) the difference in phagocytic capacity between NA1 and NA2 individuals was readily apparent with the E-ConA probe (which is independent of Fc gamma RII) and (b) the difference in phagocytosis of EA was magnified by Fc gamma RII blockade. The demonstration that allelic polymorphisms in Fc gamma R can have significant consequences for physiological functions implies that within the structural complexity of human Fc gamma Rs, including both allelic forms and cell type-specific isoforms, there will be differences in quantitative, and perhaps qualitative, function with potential importance for disease processes.
Hypersensitivity to environmental allergens in HIV-infected patients: Is atopy more frequent?
Authors: P. Mantilla Guevara, D.D. Delgado Chacón, A. Monzón de Orozco, P. Salazar, G. González, C.M. Galizia Zambrano, Y. Millán, V.A. Qintero Parada, G.R. Hernandez Vivas
Journal: Journal of Allergy and Clinical Immunology (2005)
Immunologic mechanisms in hypersensitivity reactions to metal ions: an overview
Authors: Lioba Büdinger, Michael Hertl, Lioba Büdinger
Journal: Allergy (2000)

Metal ions such as Ni 2+ , Co 2+ , Cu 2+ , or Cr 3+ are haptens with a high immunogenic potential, as contact dermatitis caused by ionic metals occurs in about 10–15% of the human population. Since alloys containing Ni 2+ , Co 2+ , and Cr 3+ are components of implants in replacement surgery, dentures, orthodontic wires, and various other devices, adverse reactions to metal ions create serious problems in practical medicine as incompatibility reactions to metal‐containing biomaterials. On the other hand, contact dermatitis to metal ions such as Ni 2+ is a well‐established model for studying the molecular mechanisms involved in the recognition of haptens by the immune system. Although many investigations have been performed to elucidate the molecular interactions causing contact hypersensitivity in man, many aspects remain to be clarified. This review will focus on the experimental data accumulated so far on the immunologic mechanisms responsible for the recognition of metal ions by T cells and eliciting adverse immune reactions causing contact dermatitis.
The Added Value of Spiral Computed Tomographic Angiography After Lung Scintigraphy for the Diagnosis of Pulmonary Embolism
Authors: L Radan, M Mor, S Gips, D Schlag-Eisenberg, Y Lurie, K Dickstein, H Bitterman, S Ben-Haim
Journal: Clinical Nuclear Medicine (2004)

Objectives: The objectives of this study were to evaluate the added clinical value of spiral computed tomographic angiography (CTA) after ventilation-perfusion lung scintigraphy (V/Q) for the management of patients with suspected pulmonary embolism (PE). Methods: Of 987 patients who had V/Q during 2001, 64 patients (6%) had CTA performed for further evaluation. V/Q and CTA findings were retrospectively analyzed by 2 clinicians who were blinded to the patients’ outcome. Patient management was determined based on clinical and V/Q data and was reassessed after the addition of CTA data. Results: CTA was performed in 2 patients with normal V/Q, 16 patients with low probability, 28 patients with intermediate, 4 patients with high probability, and 14 patients with nonconclusive V/Q. Three patients (19%) with low probability, 9 (32%) with intermediate probability, 4 (29%) with nonconclusive, and 4 (100%) with high probability V/Q had PE diagnosed by CTA. CTA findings changed the management in 2 patients (13%) with low probability, 15 (54%) with intermediate probability, and 4 (29%) with nonconclusive V/Q. Conclusion: In our institution, V/Q remains the main imaging modality for evaluation of patients with clinically suspected PE. CTA was performed after V/Q in 6% of patients. Patients with intermediate probability and those with nonconclusive V/Q, and to a much lesser extent, patients with low probability V/Q could benefit from the addition of CTA after V/Q. In patients with normal V/Q and those with high-probability V/Q, the addition of CTA does not seem to influence patient management.
Bronchography without Surface Anaesthesia
Authors: E. F. B. Cadman
Journal: BMJ (1949)

To study the functional role of activated astrocytes in glutamate homeostasis <i>in vivo</i>, we used a model of sustained astrocytic activation in the rat striatum through lentiviral-mediated gene delivery of ciliary neurotrophic factor (CNTF). CNTF-activated astrocytes were hypertrophic, expressed immature intermediate filament proteins and highly glycosylated forms of their glutamate transporters GLAST and GLT-1. CNTF overexpression produced a redistribution of GLAST and GLT-1 into raft functional membrane microdomains, which are important for glutamate uptake. In contrast, CNTF had no detectable effect on the expression of a number of neuronal proteins and on the spontaneous glutamatergic transmission recorded from striatal medium spiny neurons. These results were replicated <i>in vitro</i> by application of recombinant CNTF on a mixed neuron/astrocyte striatal culture. Using microdialysis in the rat striatum, we found that the accumulation of extracellular glutamate induced by quinolinate (QA) was reduced threefold with CNTF. In line with this result, CNTF significantly increased QA-induced [<sup>18</sup>F]-fluoro-2-deoxyglucose uptake, an indirect index of glutamate uptake by astrocytes. Together, these data demonstrate that CNTF activation of astrocytes <i>in vivo</i> is associated with marked phenotypic and molecular changes leading to a better handling of increased levels of extracellular glutamate. Activated astrocytes may therefore be important prosurvival agents in pathological conditions involving defects in glutamate homeostasis.