tbuckley/cabot-search huggingface dataset:
Food-poisoning in Sheffield in 1949
Authors: E. L. M. Millar, M. Pownall
Journal: BMJ (1950)

protection for aeroplane pilots, greenhouse sprayers, or those handling concentrated parathion in enclosed spaces.Moreover, up to 16 mg. of parathion may filter through in an eight-hour period, and this together with absorption through the skin around the mask may constitute a fatal dose.Several accidents, some fatal, have occurred where faulty or untested respirators have been used.Protective clothing, including socks and underclothing, must be laundered each day.Adequate facilities for wash- ing must be available and persons exposed to parathion are advised to remoVe all working clothes and take a bath at the end of each day's work.If parathion is splashed on to clothing this must be changed completely, and all areas of the skin which have been in contact with the soiled clothing must be washed immediately.The hands and face should be washed thoroughly in hot water and soap before eating and smoking.Whereas these pre- cautions may be enforced in factories it is almost impossible to ensure that they are carried out in the field.Routine estimations of cholinesterase activity of plasma and red blood cells should be made at weekly intervals in all persons exposed to parathion, H.E.T.P. and T.E.P.P. Davies and Rutland (1950) have investigated the variation in cholinesterase activity of plasma and red blood cells in 200 healthy adults of both sexes.Normal activity may vary from the mean by as much as 40 % (see Table ).Moreover, Plasnma and Red Blood Cell Cholinesterase: Normal Limits of
Management of Lung Cancer in Older Adults
Authors: A. Hurria, M. G. Kris
Journal: CA A Cancer Journal for Clinicians (2003)

Lung cancer is the leading cause of cancer death in the United States. At the time of diagnosis, most patients are older than 65 years and have Stage III or IV disease. More than 80% of patients have non-small cell lung cancer and the rest have small cell lung cancer. Age is not a significant prognostic factor for overall survival and response to treatment for patients with either type of lung cancer. Treatment options should be tailored to older patients based on the same selection process and benefits seen in the population as a whole. This article reviews the available data regarding surgery, radiation, and systemic treatment for older patients with lung cancer and considers the role of geriatric assessment in the evaluation of older patients.
Shift work and cancer
Authors: L. Fritschi
Journal: BMJ (2009)

cAMP-elevating drugs are thought to mediate their biological effects by activating the cAMP/cAMP-dependent protein kinase (PKA) cascade. However, this hypothesis is difficult to confirm due to a lack of selective inhibitors. Here, we have probed the role of PKA in mediating inhibitory effects of several cAMP-elevating drugs in BEAS-2B epithelial cells using an adenovirus vector encoding a PKA inhibitor protein (PKIα) and have compared it to H-89, a commonly used small molecule PKA inhibitor. Initial studies established efficient gene transfer and confirmed functionality of PKIα 48 h after virus infection. All cAMP-elevating drugs tested promoted the phosphorylation of cAMP response element-binding protein (CREB), activated a cAMP response element (CRE)-driven luciferase reporter gene, and suppressed both granulocyte/macrophage colony-stimulating factor (GM-CSF) generation and [<sup>3</sup>H]arachidonic acid (AA) release in response to interleukin-1β and monocyte chemotactic protein (MCP)-1, respectively. These effects were abolished by PKIα. In contrast, H-89 behaved unpredictably under the same conditions. Thus, although CREB phosphorylation evoked by a range of cAMP-elevating drugs was abolished by H-89, neither activation of the CRE-dependent luciferase reporter gene construct nor the inhibition of GM-CSF generation was inhibited. Paradoxically, H-89 antagonized MCP-1-induced [<sup>3</sup>H]AA release and enhanced the inhibitory effect of submaximal concentrations of rolipram and 8-bromo-cAMP. We suggest that expression of PKIα in susceptible cells provides a simple and unambiguous way to assess the role of PKA in cAMP signaling and to probe the mechanism of action of other drugs and cAMP-dependent responses where the participation of PKA is equivocal. Furthermore, these data suggest that H-89 is not a selective inhibitor of PKA and should be avoided.
The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formation
Authors: Camilla Nilsberth, Anita Westlind-Danielsson, Christopher B. Eckman, Margaret M. Condron, Karin Axelman, Charlotte Forsell, Charlotte Stenh, Johan Luthman, David B. Teplow, Steven G. Younkin, Jan Näslund, Lars Lannfelt
Journal: Nature Neuroscience (2001)
Mass spectrometric analysis of tobacco-specific hemoglobin adducts.
Authors: G Schäffler, C Betz, E Richter
Journal: Environmental Health Perspectives (1993)

Hemoglobin adducts of the common metabolite of the tobacco-specific nitrosamine (TSNA) 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) and of 4-aminobiphenyl (4-ABP) were quantified in blood samples from smokers and nonsmokers to test their suitability for biomonitoring tobacco smoke exposure. Additionally, TSNA adducts were measured in nasal snuff users. Mild alkaline treatment of hemoglobin releases 4-ABP and HPB, which were analyzed in parallel by capillary gas chromatography with electronic impact or negative ion chemical-ionization mass spectrometry (EI- or NICI-GC-MS). Samples of snuff users showed high levels of HPB adducts not correlated with the amount or type of snuff used. HPB concentrations in smokers and nonsmokers, however, were much lower, with no group-specific differences detectable. In contrast, 4-ABP adduct levels were much higher in smokers than in nonsmokers, confirming the significant difference between these two groups reported by others.
Wide-Complex Tachycardia in a Patient With Coronary Disease—Quiz Case
Authors: Eric S. Williams, Mohan N. Viswanathan, Jordan M. Prutkin
Journal: JAMA Internal Medicine (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Adenosine Modulates Cardiovascular Functions Through Activation of Extracellular Signal-Regulated Kinases 1 and 2 and Endothelial Nitric Oxide Synthase in the Nucleus Tractus Solitarii of Rats
Authors: Wen-Yu Ho, Pei-Jung Lu, Michael Hsiao, Hwong-Ru Hwang, Yu-Chou Tseng, Mao-Hsiung Yen, Ching-Jiunn Tseng
Journal: Circulation (2008)

The nucleus tractus solitarius (NTS) is the primary integrative center for baroreflex. Adenosine has been shown to play an important modulatory role in blood pressure control in the NTS. Our previous results demonstrated that adenosine decreases blood pressure, heart rate, and renal sympathetic nerve activity and modulates baroreflex responses in the NTS. We also demonstrated that a nitric oxide synthase (NOS) inhibitor may block the cardiovascular effects of adenosine in the NTS, which suggests interaction between the adenosine receptor and NOS. However, the signaling mechanisms of adenosine that induce nitric oxide release in the NTS remain uncertain. The aim of the present study was to investigate the possible signal pathways involved in the cardiovascular regulation of adenosine in the NTS.Adenosine was microinjected into the NTS of urethane-anesthetized male Sprague-Dawley rats. Blood pressure and heart rate decreased significantly after microinjection. The cardiovascular effects of adenosine were attenuated by prior administration of the mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor PD98059 (6 nmol/60 nL) or an endothelial NOS-selective inhibitor, L-NIO (6 nmol/60 nL); however, the neuronal NOS-specific inhibitor vinyl-L-NIO (600 pmol/60 nL) did not attenuate the cardiovascular effects of adenosine. Western blot and immunohistochemistry studies demonstrated that adenosine induced extracellular signal-regulated kinases 1 and 2 and endothelial NOS phosphorylation in the NTS. Pretreatment with PD98059 diminished the endothelial NOS phosphorylation evoked by adenosine.These results represent a novel finding that extracellular signal-regulated kinases 1 and 2 is involved in cardiovascular regulation in the NTS. They also indicate that the cardiovascular modulatory effects of adenosine in the NTS are accomplished by activation of mitogen-activated protein kinase/extracellular signal-regulated kinases 1 and 2 and then endothelial NOS.
Some factors affecting bubble formation with catheter-mediated defibrillator pulses.
Authors: G H Bardy, F Coltorti, T D Ivey, C Alferness, M Rackson, K Hansen, R Stewart, H L Greene
Journal: Circulation (1986)

Factors affecting bubble formation during delivery of defibrillator pulses to arrhythmogenic cardiac tissue via a catheter are unknown. We investigated the role of energy, electrode surface area, interelectrode distance, and electrode polarity on bubble formation and on current and voltage waveforms during delivery of damped sinusoidal discharges from a standard defibrillator to anticoagulated bovine blood. Gas composition was studied with mass spectrometry. Defibrillator energy settings were varied between 5 and 360 J. The principal catheter used for study was a Medtronic 6992A lead. Additional electrodes tested included 2, 5, and 10 mm long No. 6F, 7F, and 8F copper electrodes. Interelectrode distances used to assess the effect of anode-cathode spacing were 1, 5, 10, and 20 cm. Bubble volume increased linearly from 0.043 to 0.134 ml per cathodal pulse and from 0.030 to 3.50 ml per anodal pulse as energy settings were increased from 5 to 360 J (r = .99). Typical smooth waveforms for both current and voltage were seen only in the absence of bubbles. The voltage waveform was distorted for each cathodal pulse of 100 J or more and for each anodal pulse of 10 J or more only if bubbles were present. The effect of electrode surface area on bubble formation was tested at a 200 J energy setting and at a 10 cm interelectrode distance with the use of cathodal pulses. Bubble formation varied inversely with electrode surface area (r = .876). Bubble formation, however, varied minimally as interelectrode spacing was changed from 1 to 20 cm. The effect of polarity on bubble formation when the Medtronic 6992A distal electrode and an 8.5 cm disk electrode separated by 10 cm were used was highly significant. For a 200 J pulse, bubble formation with the catheter as anode was 3.30 +/- 0.10 ml and with the catheter as cathode it was 0.070 +/- 0.002 ml (p less than .001). Mass spectrometry of both anodal and cathodal gas samples demonstrated the constituents of the gas bubble to include a variety of gases, which is inconsistent with simple electrolytic production of the bubbles observed. The predominance of nitrogen in either polarity sample suggested that the principal source of the bubble was dissolved air. In summary, bubble formation at an electrode receiving damped sinusoidal outputs from a standard defibrillator does not vary significantly with varying interelectrode distance. However, it is directly proportional to energy and inversely proportional to electrode surface area. Anodal catheter discharges produce considerably more bubbles than do cathodal discharges.(ABSTRACT TRUNCATED AT 400 WORDS)
Expression of Slow Skeletal Troponin I in Hearts of Phospholamban Knockout Mice Alters the Relaxant Effect of β-Adrenergic Stimulation
Authors: Beata M. Wolska, Grace M. Arteaga, James R. Peña, Grzegorz Nowak, Ronald M. Phillips, Shalini Sahai, Pieter P. de Tombe, Anne F. Martin, Evangelia G. Kranias, R. John Solaro
Journal: Circulation Research (2002)

β-Adrenergic stimulation of the heart results in an enhanced relaxation rate in association with phosphorylation of both cardiac troponin I (cTnI) and phospholamban (PLB). We studied new lines of mice generated by crossbreeding mice that express slow skeletal troponin I (ssTnI) with PLB knockout (PLBKO) mice. This crossbreeding resulted in the generation of PLB/cTnI, PLB/ssTnI, PLBKO/cTnI, and PLBKO/ssTnI mice. Perfusion with isoproterenol (ISO) significantly increased the peak amplitude of fura-2 ratio in PLB/cTnI, PLBKO/cTnI, and PLBKO/ssTnI groups of mice. However, in the presence of ISO, there were no differences in the peak amplitude of fura-2 ratio among cells isolated from hearts of PLB/cTnI, PLBKO/cTnI, and PLBKO/ssTnI mice. In cells from PLB/cTnI mice, the extent of shortening was increased and the time of relaxation was significantly decreased during β-adrenergic stimulation. In PLBKO/cTnI cells, stimulation with ISO resulted in an increased extent of shortening and no change in time of relaxation. However, stimulation with ISO in cells isolated from PLBKO/ssTnI mice not only significantly increased the extent of cell shortening but also increased the time of relaxation. We also determined the kinetics of relaxation of papillary muscles isolated from all four groups of animals in the presence and absence of ISO. Perfusion with ISO increased the rate of relaxation only in PLB/cTnI, PLB/ssTnI, and PLBKO/cTnI muscles. During ISO stimulation, the time of relaxation was unchanged in PLBKO/ssTnI muscles. Our data directly demonstrate that phosphorylation of both PLB and cTnI contributes to increased rate of relaxation during β-adrenergic stimulation.
99mTc-Pyrophosphate Uptake in Drug-induced Gynecomastia
Authors: PARSHAN S. RamSINGH, S PUJARA, JOSEPH R. LOGIC
Journal: Clinical Nuclear Medicine (1977)

From the Mt. Sinai School of Medicine of the City University of New York and Mt. Sinai Services-City Hospital Center at Elmhurst, Elmhurst, New York
Treatment of chronic hepatitis C: A systematic review
Authors: Geetanjali Chander, Mark S. Sulkowski, Mollie W. Jenckes, Michael S. Torbenson, Franklin H. Herlong, Eric B. Bass, Kelly A. Gebo
Journal: Hepatology (2002)

This systematic review addressed 3 issues regarding current treatments for chronic hepatitis C: (1) efficacy and safety in treatment-naive patients; (2) efficacy and safety in selected subgroups of patients; and (3) effects on long-term clinical outcomes. Electronic databases were searched for articles from January 1996 to March 2002. Additional articles were identified by searching references in pertinent articles and recent journals and by questioning experts. Articles were eligible for review if they reported original human data from a study that used virological, histological, or clinical outcome measures. For data collection, paired reviewers assessed the quality of each study and abstracted data. This systematic review found that the combination of high-dose peginterferon and ribavirin was more efficacious than standard interferon and ribavirin in persons infected with hepatitis C virus (HCV) genotype 1 (sustained virologic response [SVR] rate: 42% vs. 33%) and that ranges of SVR rates were higher with peginterferon than standard interferon monotherapy in naïve patients (10% to 39% vs. 3% to 19%). Reports were consistent in showing treatment with interferon and ribavirin was more efficacious than interferon monotherapy in treatment-naive persons and previous nonresponders and relapsers. Studies were moderately consistent in showing that treatment decreases the risk for hepatocellular carcinoma (HCC). The evidence on treatment in important subgroups was limited by a lack of randomized controlled trials. Thus, the combination of peginterferon and ribavirin was the most efficacious treatment in patients with HCV genotype 1. Long-term outcomes were improved in patients with hepatitis C who achieved an SVR with treatment.
PARTIAL OCCLUSION OF THE PULMONARY AORTA AND INFERIOR VENA CAVA WITH THE METALLIC BAND. OBSERVATIONS ON CHANGES IN THE VESSEL WALL AND IN THE HEART
Authors: Mont R. Reid
Journal: The Journal of Experimental Medicine (1924)

In dogs a constricting metallic band does not affect the integrity of the wall of the vena cava, whereas it leads to a rapid death of the wall of the aorta, and, as evidenced by a single instance studied, to a much slower death of the pulmonary artery. In the instance, just mentioned, constriction of the common pulmonary artery by an aluminum band for a period of 2(1/2) years led to a right ventricular hypertrophy.
Catecholamines are mitogenic in 3T3 and bovine aortic endothelial cells.
Authors: P Sherline, R Mascardo
Journal: Journal of Clinical Investigation (1984)

We have found that catecholamines stimulate DNA synthesis and centrosomal separation in 3T3 and bovine aortic endothelial cells cultured in the absence of serum or added growth factors. The mitogenic effect is mediated by an alpha 1-adrenergic receptor, as it is inhibited by phentolamine and prazosin but not by propranolol or yohimbine. The physiological and pathological consequences of this effect remain to be determined.
The effect of digitalis on refractoriness of the intact canine His-Purkinje system.
Authors: J A Gomes, A N Damato, G A Bobb, S H Lau
Journal: Circulation (1978)

The effect of therapeutic doses of digitalis on functional (F), relative (R) and effective (E) refractory periods (RP) of the His-Purkinje system (HPS) was studied in 12 open-chested, innervated adult mongrel dogs (10-20 kg) during control and 15, 30 and 45-60 min after 0.016 mg/kg of intravenous ouabain. To determine the stability of the preparation and to assess time-dependent changes in His-Purkinje refractoriness, another six dogs (Group II) had similar studies, but without drug administration. In all dogs, the His bundle was paced by using the plunge wire technique at a predetermined cycle length (CL) and a premature stimulus (S2) to the His bundle was introduced at decreasing S1 S2 intervals. Following ouabain, in Group I dogs, at the longest Cls tested (458 +/- 125 msec; +/- SD) there was significant increase in the FRP (+4.34%; P less than 0.05), RRP (S2 V2 (+6.57%, P less than 0.05), RRP (Ab) (+6%, P less than 0.05) and ERP (52%, P less than 0.05) of the HPS. These significant changes were generally observed 30 minutes after drug administration. Changes in RPs were of greater magnitude at longer CLs (greater than 400 msec), but insignificant at shorter CLs (less than 400 msec). The H-V interval during sinus rhythm and the S1 V1 interval during His bundle pacing at all CLs did not change after ouabain. In Group II dogs there were no significant change in His-Purkinje refractoriness over 60 minutes. These findings suggest that therapeutic doses of digitalis 1) tend to increase refractoriness within the HPS to a very small degree, 2) have no appreciable effect on His-Purkinje conduction, and 3) affect CL-dependent changes in refractoriness. The His bundle extrastimulus method is useful in studying the HPS in the intact heart.
Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin
Authors: Massimo Collino, Christoph Thiemermann, Anthony Cerami, Michael Brines
Journal: Pharmacology & Therapeutics (2015)

Many disease processes activate a cellular stress response that initiates a cascade of inflammation and damage. However, this process also triggers a tissue protection and repair system mediated by locally-produced hyposialated erythropoietin (hsEPO). Although recombinant EPO is used widely for treating anemia, potential use of recombinant EPO for tissue-protection is limited by rises in hematocrit, platelet activation, and selectin expression resulting in a high risk of thrombosis. Importantly, the erythropoietic and tissue-protective effects of EPO are mediated by different receptors. Whereas EPO stimulates red cell progenitors by binding to an EPO receptor (EPOR) homodimer, a heterodimer receptor complex composed of EPOR and β common receptor (βcR) subunits, termed the innate repair receptor (IRR), activates tissue protection and repair. The IRR is typically not expressed by normal tissues, but instead is rapidly induced by injury or inflammation. Based on this understanding, EPO derivatives have been developed which selectively activate the IRR without interacting with the EPOR homodimer. The latest generation of specific ligands of the IRR includes an 11 amino acid peptide modeled from the three dimensional structure of the EPO in the region of helix B called pyroglutamate helix B surface peptide (pHBSP; ARA-290). Despite a short plasma half-life (~2min), pHBSP activates a molecular switch that triggers sustained biological effects that have been observed in a number of experimental animal models of disease and in clinical trials. This review summarizes pharmacokinetic and pharmacodynamic data and discusses the molecular mechanisms underlying the long-lasting effects of this short-lived peptide.
Identification of SUPT3H as a novel 8q24/MYC partner in blastic plasmacytoid dendritic cell neoplasm with t(6;8)(p21;q24) translocation
Authors: Y Nakamura, H Kayano, E Kakegawa, H Miyazaki, T Nagai, Y Uchida, Y Ito, N Wakimoto, S Mori, M Bessho
Journal: Blood Cancer Journal (2015)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) (previously referred as blastic natural killer cell leukemia/lymphoma or agranular CD4+/CD56+ hematodermic neoplasm) is a rare hematologic malignancy derived from the precursors of plasmacytoid dendritic cells and is now classified as a rare subtype of acute myeloid leukemia according to the 2008 WHO classification. 1 The disease is a clinically aggressive tumor with a high frequency of cutaneous and bone marrow (BM) involvement.Tumor cells express CD4, CD43, CD45RA and CD56, as well as the plasmacytoid dentritic cell-associated antigens CD123, BDCA-2/ CD303, TCL1 and CTLA1.The pathogenesis of BPDCN is largely unknown.