tbuckley/cabot-search huggingface dataset:
Botulinum Toxin and Other New Approaches to Migraine Therapy
Authors: Avi Ashkenazi, Stephen D. Silberstein
Journal: Annual Review of Medicine (2004)

The number of migraine treatments and our understanding of migraine pathophysiology are both increasing. Newer treatments focus on migraine prevention. Botulinum toxin (BTX) is a potent neurotoxin used primarily to treat diseases associated with increased muscle activity. Recently, BTX was found to have antinociceptive effects that are probably independent of its muscle-relaxant action. Clinical trials support the efficacy of BTX type A (and possibly also type B) in the treatment of migraine. The anticonvulsant topiramate was recently shown to be effective for migraine prevention. At the low doses used for this indication, cognitive side effects are not a major concern. Another new approach to migraine prevention is angiotensin type 1 (AT1) receptor blockade. The high tolerability of the AT1 receptor blocker candesartan warrants further studies to assess its role in migraine prevention.
Prevalence of chronic liver disease in the general population of northern Italy: The dionysos study
Authors: Stefano Bellentani, Claudio Tiribelli, Gioconda Saccoccio, Marino Sodde, Nicoletta Fratti, Christina De Martin, Giovanni Christianini
Journal: Hepatology (1994)

Data on the prevalence of chronic liver disease, derived from selected series of hospitalized patients or from mortality registers, underestimate the prevalence of chronic liver disease. The Dionysos Study is a cohort study that investigated for the first time the prevalence of chronic liver disease in a general population. All the citizens of two towns in northern Italy, Campogalliano and Cormons, aged 12 to 65 yr were contacted by letter. From March 1991 through March 1993, 6,917 of a total of 10,150 citizens were enrolled (compliance, 69%). The standardized protocol for each enrollee included (a) a color-illustrated food questionnaire on dietary habits and alcohol intake; (b) a detailed medical history, including questions on risk factors for chronic liver disease; (c) a physical examination; and (d) blood tests for AST, ALT, γ-glutamyl-transpeptidase, mean cell volume, platelet count and hepatitis B virus and hepatitis C virus markers. Signs suggestive of chronic liver disease were seen in 21.3% of the subjects, and who then underwent further liver function tests, upper abdominal ultrasonography and, when necessary, liver biopsy. Persistent signs of chronic liver disease were present in 17.5% of the subjects, including 1.1% with cirrhosis and 0.07% with hepatocellular carcinoma. The prevalence rates of hepatitis B virus and hepatitis C virus positivity (second-generation enzyme-linked immunosorbent assay) were 1.3% and 3.2%, respectively. Alcohol abuse was the etiological agent in 23%. Other factors which predisposed subjects to chronic liver disease were age older than 35 yr, male sex, body mass index higher than 27, history of blood transfusion, drug addiction and presence of chronic liver disease in the subject's family. Cirrhosis was due to hepatitis B virus or hepatitis C virus in 37%, and alcohol was the cause in 26%. In those subjects with alcohol abuse, viral infection, especially hepatitis C virus, played an important role in the deterioration of chronic liver disease and its progression to hepatocellular carcinoma. We conclude that the Dionysos study, the first study of the prevalence of chronic liver disease in a general population of northern Italy, found a much higher prevalence of chronic liver disease than reported previously in selected populations from Western countries. Hepatitis viral infections and alcoholism were the most important causative agents. (Hepatology 1994;20:1442-1449).
Effect of different sample volumes on the DNA extraction of Aspergillus fumigatus from whole blood
Authors: B. Schulz, K. Weber, C. Radecke, C. Scheer, M. Ruhnke
Journal: Clinical Microbiology and Infection (2009)

Five methods were compared, using conventional PCR, for the isolation of DNA from Aspergillus fumigatus conidia from 1–3-mL samples of whole blood. A lower detection threshold of Aspergillus conidia was achieved using 3-mL rather than 1-mL samples with three of five methods tested.
The Calcium-Sensing Receptor: A Molecular Perspective
Authors: Aaron L. Magno, Bryan K. Ward, Thomas Ratajczak
Journal: Endocrine Reviews (2011)

Abstract Compelling evidence of a cell surface receptor sensitive to extracellular calcium was observed as early as the 1980s and was finally realized in 1993 when the calcium-sensing receptor (CaR) was cloned from bovine parathyroid tissue. Initial studies relating to the CaR focused on its key role in extracellular calcium homeostasis, but as the amount of information about the receptor grew it became evident that it was involved in many biological processes unrelated to calcium homeostasis. The CaR responds to a diverse array of stimuli extending well beyond that merely of calcium, and these stimuli can lead to the initiation of a wide variety of intracellular signaling pathways that in turn are able to regulate a diverse range of biological processes. It has been through the examination of the molecular characteristics of the CaR that we now have an understanding of how this single receptor is able to convert extracellular messages into specific cellular responses. Recent CaR-related reviews have focused on specific aspects of the receptor, generally in the context of the CaR's role in physiology and pathophysiology. This review will provide a comprehensive exploration of the different aspects of the receptor, including its structure, stimuli, signalling, interacting protein partners, and tissue expression patterns, and will relate their impact on the functionality of the CaR from a molecular perspective.
Sequences and Factors: A Guide to MHC Class-II Transcription
Authors: Laurie H. Glimcher, Catherine J. Kara
Journal: Annual Review of Immunology (1992)

The expression of the class-II antigens of the major histocompatibility complex is tissue-specific, developmentally regulated in cells of the B lineage, and inducible by cytokine. Some of the molecular mechanisms that account for this regulation have recently been elucidated. DNA sequences upstream of human and mouse class-II genes that are critical for the transcription of these genes have been identified through transfection studies and transgenic analysis. Furthermore, a number of transcription factors that bind to important promoter motifs have recently been isolated. Examination of the class-II promoter in vivo both in the normal state and in patients with bare lymphocyte syndrome has further increased our understanding of class-II regulation.
Placental Growth Factor Promotes Atherosclerotic Intimal Thickening and Macrophage Accumulation
Authors: Rohit Khurana, Lieve Moons, Shahida Shafi, Aernout Luttun, Désiré Collen, John F. Martin, Peter Carmeliet, Ian C. Zachary
Journal: Circulation (2005)

Background— Placental growth factor (PlGF) has been implicated in the pathophysiological angiogenesis and monocyte recruitment that underlie chronic inflammatory disease, but its role in atherosclerosis has not been examined. We investigated the effects of exogenous PlGF, delivered by adenoviral gene transfer, on atherogenic intimal thickening and macrophage accumulation induced by collar placement around the rabbit carotid artery and examined the effects of PlGF deficiency on atherosclerosis in apolipoprotein E–deficient (apoE −/− ) mice. Methods and Results— Periadventitial transfer of PlGF2-encoding adenoviruses significantly increased intimal thickening, macrophage accumulation, endothelial vascular cell adhesion molecule-1 expression, and adventitial neovascularization in the collared arteries of hypercholesterolemic rabbits and increased the intima-to-media ratio in rabbits fed a normal diet. Neointimal macrophages were associated with increased expression of the PlGF receptor Flt-1. The size and macrophage content of early atherosclerotic lesions were reduced in mice deficient in both apoE and PlGF compared with apoE-deficient mice. Conclusions— Local adenoviral PlGF2 delivery promotes atherogenic neointima formation in hypercholesterolemic rabbits, and PlGF is required for macrophage infiltration in early atherosclerotic lesions in apoE −/− mice. These findings support a novel role for PlGF in the pathogenesis of atherosclerotic disease.
Integrating Supportive and Palliative Care in the Trajectory of Cancer: Establishing Goals and Models of Care
Authors: Eduardo Bruera, David Hui
Journal: Journal of Clinical Oncology (2010)

Tom, a 50-year-old man with metastatic pancreatic cancer, was referred by his phase I physician to our supportive care center for symptom management. He was initially diagnosed with pancreatic cancer involving the liver approximately 6 months before this visit. He developed progressive disease despite three lines of systemic therapy, including four cycles of gemcitabine and cisplatin, three cycles of gemcitabine and vorinostat under phase I, and two cycles of fluorouracil, leucovorin, and oxaliplatin 6. His clinical course was complicated by recurrent venous thromboembolic events. Tom arrived at the supportive care clinic in a wheelchair and accompanied by his wife. He complained of right upper quadrant pain, particularly with inspiration, despite taking morphine continuous release 30 mg twice a day. He had also experienced severe fatigue, weakness, constipation, decreased appetite, and weight loss of 25 kg during the previous 5 months. Eastern Cooperative Oncology Group performance status was 4. Edmonton Symptom Assessment Scale (0 no symptom, 10 worst possible) revealed pain 8, fatigue 4, nausea 0, depression 0, anxiety 0, drowsiness 0, appetite 10, well-being 5, dyspnea 5, and sleep 5. On examination, he looked thin, was tachycardic and tachypneic, and had significant tenderness over the right upper quadrant. He was also experiencing severe weakness and had to use both hands to lift his legs to move around in bed. He lived with his wife and one son at home, but he had difficulty coping with the worsening symptoms. We adjusted his pain medications and laxatives, gave him a dose of methylnaltrexone in the clinic, recommended a home-safety evaluation, and provided supportive/expressive counseling. He expressed the desire not to receive any more cancer treatments, and we discussed the transition to hospice care so he could get more support at home. At the end of the visit, Tom said, “Oh, I wish I had seen you sooner. Why wasn’t I referred here earlier?” Tom went home with hospice care and died 10 days later.
Increased Ischemia-Induced Angiogenesis in the Staggerer Mouse, a Mutant of the Nuclear Receptor Rorα
Authors: Sandrine Besnard, Jean-Sébastien Silvestre, Micheline Duriez, Joëlle Bakouche, Yolande Lemaigre-Dubreuil, Jean Mariani, Bernard I. Levy, Alain Tedgui
Journal: Circulation Research (2001)

Rorα is an orphan nuclear receptor. In homozygous staggerer mutant mice (Rora sg/sg ), a deletion within the Rora gene leads to an overexpression of inflammatory cytokines. Because inflammation and hypoxia are 2 key stimuli of ischemia-induced angiogenesis, we studied the role of Rorα in this setting. Ischemia was induced by ligation of the right femoral artery in C57BL/6 Rora +/+ and Rora sg/sg mice. After 3 and 28 days, angiogenesis was evaluated by microangiography, measurement of capillary density using immunohistochemistry (anti-CD31), and measurement of blood flow by laser Doppler imaging. At day 3, angiographic score and blood flow were similar in Rora sg/sg mice and in Rora +/+ littermates. Conversely, at day 28, Rora sg/sg mice showed a significant 2-fold increase in angiographic score and a 3-fold increase in capillary density within the ischemic hindlimb compared with control. Functionally, this coincided with a significant rise in leg perfusion in Rora sg/sg mice (0.83±0.05 for ischemic/nonischemic leg perfusion ratio) compared with Ror +/+ mice (0.66±0.04, P &lt;0.05). In addition, more extensive angiogenesis in Rora sg/sg mice correlated with an increased expression of eNOS protein by 83±12% and 71±24% at 3 and 28 days, respectively ( P &lt;0.05), whereas the level of the antiangiogenic cytokine IL-12 was significantly reduced by 38±10% at day 28 ( P &lt;0.05). Conversely, no changes in VEGF expression were observed. Our study identifies for the first time a new role for Rorα as a potent negative regulator of ischemia-induced angiogenesis.
Multi-species integrative biclustering
Authors: Peter Waltman, Thadeous Kacmarczyk, Ashley R Bate, Daniel B Kearns, David J Reiss, Patrick Eichenberger, Richard Bonneau
Journal: Genome biology (2010)

We describe an algorithm, multi-species cMonkey, for the simultaneous biclustering of heterogeneous multiple-species data collections and apply the algorithm to a group of bacteria containing Bacillus subtilis, Bacillus anthracis, and Listeria monocytogenes. The algorithm reveals evolutionary insights into the surprisingly high degree of conservation of regulatory modules across these three species and allows data and insights from well-studied organisms to complement the analysis of related but less well studied organisms.
Specific Chemopreventive Agents Trigger Proteasomal Degradation of G1 Cyclins: Implications for Combination Therapy
Authors: Konstantin H. Dragnev, Ian Pitha-Rowe, Yan Ma, W. Jeffrey Petty, David Sekula, Bryan Murphy, Mara Rendi, Nanjoo Suh, Neil B. Desai, Michael B. Sporn, Sarah J. Freemantle, Ethan Dmitrovsky
Journal: Clinical Cancer Research (2004)

Abstract Purpose: There is a need to identify cancer chemoprevention mechanisms. We reported previously that all-trans-retinoic acid (RA) prevented carcinogenic transformation of BEAS-2B immortalized human bronchial epithelial cells by causing G1 arrest, permitting repair of genomic DNA damage. G1 arrest was triggered by cyclin D1 proteolysis via ubiquitin-dependent degradation. This study investigated which chemopreventive agents activated this degradation program and whether cyclin E was also degraded. Experimental Design: This study examined whether: (a) cyclin E protein was affected by RA treatment; (b) cyclin degradation occurred in derived BEAS-2B-R1 cells that were partially resistant to RA; and (c) other candidate chemopreventive agents caused cyclin degradation. Results: RA treatment triggered degradation of cyclin E protein, and ALLN, a proteasomal inhibitor, inhibited this degradation. Induction of the retinoic acid receptor β, growth suppression, and cyclin degradation were each inhibited in BEAS-2B-R1 cells. Transfection experiments in BEAS-2B cells indicated that RA treatment repressed expression of wild-type cyclin D1 and cyclin E, but ALLN inhibited this degradation. Mutation of threonine 286 stabilized transfected cyclin D1, and mutations of threonines 62 and 380 stabilized transfected cyclin E, despite RA treatment. Specific chemopreventive agents triggered cyclin degradation. Nonclassical retinoids (fenretinide and retinoid X receptor agonists) and a synthetic triterpenoid (2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid) each suppressed BEAS-2B growth and activated this degradation program. However, a vitamin D3 analog (RO-24–5531), a cyclooxygenase inhibitor (indomethacin), and a peroxisome proliferator-activated receptor γ agonist (rosiglitazone) each suppressed BEAS-2B growth, but did not cause cyclin degradation. BEAS-2B-R1 cells remained responsive to nonclassical retinoids and to 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid. Conclusions: Specific chemopreventive agents activate cyclin proteolysis. Yet, broad resistance did not occur after acquired resistance to a single agent. This provides a therapeutic rationale for combination chemoprevention with agents activating non-cross-resistant pathways.
FcγR-induced production of superoxide and inflammatory cytokines is differentially regulated by SHIP through its influence on PI3K and/or Ras/Erk pathways
Authors: Latha P. Ganesan, Trupti Joshi, Huiqing Fang, Vijay Kumar Kutala, Julie Roda, Rossana Trotta, Amy Lehman, Periannan Kuppusamy, John C. Byrd, William E. Carson, Michael A. Caligiuri, Susheela Tridandapani
Journal: Blood (2006)
Peptic ulcer bleeding in the elderly: relative roles of<i>Helicobacter pylori</i> and non-steroidal anti-inflammatory drugs
Authors: D J E Cullen, G M Hawkey, D C Greenwood, H Humphreys, V Shepherd, R F A Logan, C J Hawkey
Journal: Gut (1997)

Most ulcers are caused, one can deduce, by Helicobacter pylori or by use of non-steroidal anti-inflammatory drugs (NSAIDs). Whether both together are worse than one alone is something that is quite unknown.To study both factors in order to see wither they interact together positively.A case control study of ulcer bleeding in elderly patients chosen without weeding.NSAID usage increased risk substantially. So did H pylori infection (but relative risk less than three). Neither seemed to interact. Their actions were discretely intact.H pylori effects ulcer bleeding in an adverse manner but does not make the risk of NSAIDs worse.
Cardiovascular and neurohumoral postural responses and baroreceptor abnormalities during a course of adjunctive vasodilator therapy with felodipine for congestive heart failure.
Authors: E Kassis, O Amtorp
Journal: Circulation (1987)

Studies in patients with congestive heart failure (CHF) have demonstrated an abnormal beta-adrenergic reflex vasodilation during orthostatic tilt. Baroreflex modulation of vascular resistance in patients with CHF was investigated during therapy with a vasoselective calcium antagonist, felodipine. Eight patients on conventional therapy for severe CHF were studied after a 3 week course of additional felodipine or placebo treatment under randomized, double-blind, and crossover conditions. Forearm subcutaneous vascular resistance (FSVR) was estimated with use of the local 133Xe washout. Aortic pulsatile stretch, expressed as the systolic distension in percent of diastolic diameter, was calculated from echocardiographic measurements of aortic root diameters. At 3 weeks, felodipine reduced the arterial pressure, systemic vascular resistance, and FSVR, preserved cardiac filling pressures and heart rate, and increased cardiac output, stroke volume, and aortic pulsatile stretch. Upright tilt (45 degrees) was used to study baroreflex-mediated cardiovascular responses. The unloading of cardiopulmonary baroreceptors during upright tilt was substantial and about equal during both treatment courses, but the pulse pressure was maintained during the placebo and decreased during the felodipine period. During tilt, the patients on placebo failed to increase heart rate and their FSVR, systemic vascular resistance, and arterial mean pressure were decreased, whereas during tilt after felodipine, heart rate and systemic vascular resistance increased to maintain arterial mean pressure and FSVR also tended to increase. Both the stroke volume and aortic pulsatile stretch increased during tilt in patients on placebo but they decreased in those on felodipine. The tilt caused increments in circulating norepinephrine and epinephrine levels during both treatment regimens. Regulation of FSVR during the sympathetic stimulation of orthostatic stress was further elucidated. Proximal neural blockade caused an increase in FSVR during tilt in patients on placebo and a decrease in FSVR during tilt in those on felodipine. Local beta-adrenoceptor blockade caused similar increments in FSVR during tilt in patients on both treatments. Combined proximal and local blockade still increased FSVR during tilt in those on placebo, but caused no change in FSVR during tilt in those on felodipine. This study demonstrates that felodipine normalizes baroreflex control of vascular resistance in patients with CHF.(ABSTRACT TRUNCATED AT 250 WORDS)
Epicardial Coronary Artery Compliance in the Dog
Authors: JOHN E. DOUGLAS, JOSEPH C. GREENFIELD
Journal: Circulation Research (1970)

The dynamic compliance of 21 coronary arteries from 17 dogs was determined in situ. Intramyocardial portions were occluded with a mixture of 200µ glass beads and liquid silicone. To simulate in vivo pressure-volume conditions, 0.1 ml of saline was injected in 150 to 240 msec at a rate of 30 pulses/min. Silicone casts of the vessels, made at 100 mm Hg distending pressure, were used as a reference volume. The results indicate that the dynamic compliance decreases as the initial distending pressure rises. The change in volume for a 50 mm Hg pressure increment (initial distending pressure of 100 mm Hg) was 3.7 ± 0.6% (mean ± SE). In four dogs, phasic flow in the left circumflex coronary artery was measured. The volume of systolic flow per beat during the control state was of the same order of magnitude as the compliance of the vessels; however, during reactive hyperemia, systolic coronary flow markedly exceeded the dynamic compliance of the coronary vessels. In six dogs the static compliance of a segment of coronary artery was obtained radiographically. A 30.1 ± 1.4% change in volume occurred when the intravascular pressure was increased from 70 to 120 mm Hg.
The Aryl Hydrocarbon Receptor: Multitasking in the Immune System
Authors: Brigitta Stockinger, Paola Di Meglio, Manolis Gialitakis, João H. Duarte
Journal: Annual Review of Immunology (2014)

The aryl hydrocarbon receptor (AhR), for many years almost exclusively studied by the pharmacology/toxicology field for its role in mediating the toxicity of xenobiotics such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has more recently attracted the attention of immunologists. The evolutionary conservation of this transcription factor and its widespread expression in the immune system point to important physiological functions that are slowly being unraveled. In particular, the emphasis is now shifting from the role of AhR in the xenobiotic pathway toward its mode of action in response to physiological ligands. In this article, we review the current understanding of the molecular interactions and functions of AhR in the immune system in steady state and in the presence of infection and inflammation, with a focus on barrier organs such as the skin, the gut, and the lung.
ANTI‐ASTHMATIC PROPERTIES OF A NEW PERORAL DRUG (HC 20–511.)
Authors: J. P. GIRARD, M. CUEVAS
Journal: Allergy (1977)

A clinical trial was performed with a new substance (HC 20-511) derived from the cycloheptothiophene group used in the management of asthma. Twenty-four asthma patients were treated at random, with HC 20-511 or placebo or the antihistaminic substance, clemastin (Tavegyl). A statistical evaluation of the results unequivocally demonstrates good protection with a single dose of 2.0 mg or two times 1.0 mg for 3 days against a challenging antigen, compared with the placebo or the antihistaminic agent. Tolerance was excellent.