tbuckley/cabot-search huggingface dataset:
Mitochondrial metabolism of pyruvate is required for its enhancement of cardiac function and energetics
Authors: R Mallet
Journal: Cardiovascular Research (1999)

Pyruvate augmentation of contractile function and cytosolic free energy of ATP hydrolysis in myocardium could result from pyruvate catabolism in the mitochondria or from increased ratio of the cytosolic NAD+/NADH redox couple via the lactate dehydrogenase equilibrium. Objective: To test the hypothesis that cytosolic oxidation by pyruvate is sufficient to increase cardiac function and energetics. Methods: Isolated working guinea-pig hearts received 0.2 mM octanoate±2.5 mM pyruvate as fuels. α-Cyano-3-hydroxycinnamate (COHC, 0.6 mM) was administered to selectively inhibit mitochondrial pyruvate uptake without inhibiting pyruvate's cytosolic redox effects or octanoate oxidation. The effects of pyruvate and COHC on sarcoplasmic reticular Ca2+ handling were examined in 45Ca-loaded hearts. Results: Pyruvate increased left ventricular stroke work and power 40%, mechanical efficiency 29%, and cytosolic ATP phosphorylation potential nearly fourfold. 14CO2 formation from [1-14C]pyruvate was inhibited 65% by COHC, and octanoate oxidation, i.e. 14CO2 formation from [1-14C]octanoate, concomitantly increased threefold. COHC prevented pyruvate enhancement of left ventricular function, mechanical efficiency and cytosolic phosphorylation potential, but did not alter respective levels in pyruvate-free control hearts and augmented cytosolic oxidation by pyruvate. Pyruvate increased sarcoplasmic reticular Ca2+ turnover, i.e. Ca2+ uptake and release, as indicated by 62% decrease in caffeine-induced 45Ca release following 40 min 45Ca washout (P<0.01). In presence of COHC, pyruvate did not lower caffeine-induced 45Ca release; thus, COHC abrogated pyruvate enhancement of Ca2+ turnover (P<0.001). Conclusion: Pyruvate oxidation of cytosolic redox state is not sufficient to increase cardiac function, cytosolic energetics and sarcoplasmic reticular Ca2+ turnover when mitochondrial pyruvate transport is disabled; thus, mitochondrial metabolism of pyruvate is essential for its metabolic inotropism.
THE PROPOSED INTERNATIONAL MEDICAL INSIGNIA.
Authors: R. FRENCH STONE
Journal: JAMA (1896)

Since the recent publication of various articles with reference to the above subject have appeared in the leading medical journals of this country, and especially of those from the editorial pens of the Boston<i>Medical and Surgical Journal</i>, the<i>Journal of the Army and Navy</i>and of theAmerican Medical Association, much interest has been excited and great unanimity of opinion expressed concerning the symbolism and esthetics of our profession. As one phase of the development of this question it may be stated that Col. C. H. Alden, Assistant Surgeon General of the U. S. Army, has been appointed chairman of a committee to adopt insignia to distinguish the medical corps of the Army from officers in other branches of the service, and as the medical officers of the National Guard may adopt the same design he has requested the Surgeon Generals of different States to offer suggestions as to
Health professionals' advice: the ethics
Authors: E. S. Cooper
Journal: BMJ (2011)

When the speakers at the Atos recruitment evening told McCartney that they describe the assessment for the Department of Work and Pensions (DWP) as being of claimants, not patients, they were not talking about nuance of language or “sending a message.”1 The claimants are not the medical assessor’s patients. Therefore the over-riding ethical principle of the General Medical Council, “make the care of the patient your first concern” does not apply here. Medical ethics requires general probity on the …
Metabolic Staging of Lung Cancer
Authors: Salvatore U. Berlangieri, Andrew M. Scott
Journal: New England Journal of Medicine (2000)

Carcinoma of the lung is the leading cause of death from cancer in Western countries. Surgery is the treatment most likely to result in the cure of early non–small-cell lung carcinoma, which includes squamous-cell carcinoma, adenocarcinoma, and large-cell carcinoma. In contrast, at presentation small-cell lung cancer (oat-cell carcinoma) has almost always spread, and patients with this form of lung cancer are not candidates for resection. Since tumor involvement of mediastinal lymph nodes limits the chance of a surgical cure of non–small-cell lung cancer, accurate staging of disease in the mediastinum is essential. For patients with disease classified as stage I . . .
Cryoablation at the anatomically determined annular site prevents myocardial ischemia in surgery for atrial fibrillation
Authors: Hajime Imura, Takashi Nitta, Sekoh Suzuki, Daisuke Okada, Kiyomi Yamada, Shigeo Yamauchi, Shigeo Tanaka
Journal: Journal of the American College of Cardiology (2002)
Evidence from oocyte expression that the erythrocyte water channel is distinct from band 3 and the glucose transporter.
Authors: R Zhang, S L Alper, B Thorens, A S Verkman
Journal: Journal of Clinical Investigation (1991)

It has been proposed that the mercurial-sensitive water transporter in mammalian erythrocytes is the anion exchanger band 3 (AE1) and/or the glucose transporter, band 4.5 (GLUT1). Using a functional assay for water channel expression in Xenopus oocytes (Zhang, R., K. A. Logee, and A. S. Verkman. 1990. J. Biol. Chem. 265:15375-15378), we compared osmotic water permeability (Pf) of oocytes injected with water, reticulocyte mRNA, AE1 mRNA, and GLUT1 mRNA. Injection of oocytes with 5-50 ng of in vitro-transcribed AE1 mRNA had no effect on Pf, but increased trans-stimulated 36Cl uptake greater than fourfold in a dinitro-disulfonic stilbene (DNDS)-inhibitable manner. Injection with 1-50 ng of in vitro-transcribed GLUT1 mRNA increased 3H-methylglucose uptake greater than 15-fold in a cytochalasin B-sensitive manner and increased Pf from (3.7 +/- 0.4) x 10(-4) cm/s (SE, n = 16, 10 degrees C) in water-injected oocytes up to (13 +/- 1) x 10(-4) cm/s (n = 18). Both the increments in sugar and water transport were inhibited by cytochalasin B (25 microM) and phloretin (0.2 mM); neither was inhibited by 0.3 mM HgCl2. In oocytes injected with 50 ng of rabbit reticulocyte mRNA, the Pf of (18 +/- 2) x 10(-4) cm/s (n = 18) was reduced to (4.0 +/- 0.6) x 10(-4) cm/s (n = 10) by HgCl2, but was not inhibited by DNDS (0.4 mM), cytochalasin B or phloretin. Coinjection of reticulocyte mRNA with antisense oligodeoxyribonucleotides against AE1 or GLUT1 did not affect Pf, but inhibited completely the incremental uptake of 36Cl or 3H-methylglucose, respectively. Expression of size-fractionated mRNA from reticulocyte gave a 2-2.5-kb size for water channel mRNA, less than the 4-4.5-kb size for the Cl transporter. These results provide evidence that facilitated water transport in erythrocytes is mediated not by bands 3 or 4.5, but by distinct water transport protein(s).
Manter &amp;amp; Gatz's Essentials of Clinical Neuroanatomy and Neurophysiology
Authors: Lawrence C. McHenry
Journal: JAMA (1983)

There is no comparison between this new, sixth edition, and the last, fifth edition, of this useful text, originally published in 1958 by Dr Manter. Drs Gilman and Winans have completely rewritten and reorganized the text, making this now a splendid overview of the essentials of clinical neuroanatomy and neurophysiology. Although the contents are organized similarly to previous editions, the present authors have revised all sections, incorporating a number of recent advances that have occurred in our knowledge of the anatomy and physiology of the nervous system. Updated material includes mention of the enkephalins and endorphins and new methods of studying nerve denervation by the Nauta method over the usual Marchi method. It would have been appropriate to include a brief section on the physiology of the cerebral circulation and on cerebral metabolism, and to at least mention that the carotid and vertebral arteries arise from the heart and aorta
Further Use of Color Coding in Drug Evaluations
Authors: Irving W. Schiller, Francis C. Lowell
Journal: New England Journal of Medicine (1959)

TN an earlier report1 dealing with orally administered bronchodilator preparations, it was shown that information equivalent to that available by the conventional double-bind technic could be gained by the use of medications coded by color and dispensed in a single bottle. Coding by color appeared to have the advantage of simplicity and ease of administration. To validate this technic and to check its ability to supply reliable data, further inquiry was desirable. The design of such a study would use the same group of drugs coded by two different sets of colors, evaluated by the same patient. The repetitious nature . . .
Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor.
Authors: W E Carson, J G Giri, M J Lindemann, M L Linett, M Ahdieh, R Paxton, D Anderson, J Eisenmann, K Grabstein, M A Caligiuri
Journal: The Journal of Experimental Medicine (1994)

Interleukin 15 (IL-15) is a novel cytokine that has recently been cloned and expressed. Whereas it has no sequence homology with IL-2, IL-15 interacts with components of the IL-2 receptor (IL-2R). In the present study we performed a functional analysis of recombinant IL-15 on phenotypically and functionally distinct populations of highly purified human natural killer (NK) cells. The CD56bright subset of human NK cells constitutively expresses the high affinity IL-2R and exhibits a brisk proliferative response after the binding of picomolar amounts of IL-2. Using a proliferation assay, IL-15 demonstrated a very steep dose-response curve that was distinct from the dose-response curve for IL-2. The proliferative effects of IL-15 could be abrogated by anti-IL-2R beta (p75), but not by anti-IL-2R alpha (p55). The proliferative effects of IL-2 on CD56bright NK cells could be inhibited by both antibodies. CD56dim NK cells express the intermediate affinity IL-2R in the absence of the high affinity IL-2R. Activation of CD56dim NK cells by IL-15 was similar to that of IL-2 as measured by enhanced NK cytotoxic activity, antibody-dependent cellular cytotoxicity, and NK cell production of interferon gamma, tumor necrosis factor alpha, and granulocyte/macrophage colony-stimulating factor. The IL-15-enhanced NK cytotoxic activity could be completely blocked by anti-IL-2R beta monoclonal antibody. The binding of radiolabeled IL-2 and IL-15 to CD56dim NK cells was inhibited in the presence of anti-IL-2R beta. Scatchard analysis of radiolabeled IL-15 and IL-2 binding to NK-enriched human lymphocytes revealed the presence of high and intermediate affinity receptors for both ligands. IL-15 is a ligand that activates human NK cells through components of the IL-2R in a pattern that is similar but not identical to that of IL-2. Unlike IL-2, IL-15 is produced by activated monocytes/macrophages. The discovery of IL-15 may increase our understanding of how monocytes/macrophages participate in the regulation of NK cell function.
Low body mass index is a risk factor forimpaired endothelium-dependent vasodilation in humans: role of nitric oxide and oxidative stress
Authors: Yukihito Higashi, Shota Sasaki, Keigo Nakagawa, Masashi Kimura, Kensuke Noma, Satoshi Sasaki, Keiko Hara, Hideo Matsuura, Chikara Goto, Tetsuya Oshima, Kazuaki Chayama, Masao Yoshizumi
Journal: Journal of the American College of Cardiology (2003)
Difficulties with “humaniqueness”
Authors: Irene M. Pepperberg
Journal: Behavioral and Brain Sciences (2008)

Abstract Explaining the transition from nonhuman to human behavior is a major scientific problem. Penn et al. argue for discontinuous evolution; they review many relevant papers but miss some that disagree with their stance. Given the shifting ground on which Penn et al.'s theories are based, and the likelihood of future studies providing additional information on continuities, a more open approach to continuity is warranted.
Post-mortem Examinations on Air-crash Victims
Authors: D. Teare
Journal: BMJ (1951)

OXYGEN MEI 707 of the blood pressure occurred.They found that slow injections of dilute solutions minimized the undesirable effects on respiration and circulation of piperidine derivatives resembling pethidine when administered to patients under nitrous oxide and oxygen anaesthesia. SummaryThe employment of pethidine hydrochloride as an adju- vant to nitrous oxide and oxygen anaesthesia has been dis- cussed, with special reference to its anticholinergic and antihistaminic properties.A method of maintenance by a continuous intravenous pethidine drip is outlined.The importance of slow injections of dilute solutions is emphasized.
Isosorbide 5-mononitrate (ISMN) increases plasma renin activity (PRA) and aldosterone (ALD) and impairs renal function in cirrhosis with ascites
Authors: JM Salmerón, L Ruiz del Arbol, A Ginès, JC García Pagán, F Feu, P Ginès, W Jimenez, J Bosch, V Arroyo, J Rodés
Journal: Journal of Hepatology (1991)
THE DANGER OF SPINAL ANESTHESIA.
Authors: JOHN V. SHOEMAKER
Journal: JAMA (1900)

Shortly after the introduction of cocain as a local anesthetic, Dr. J. Leonard Corning, of New York, demonstrated that it was possible, under its influence, to remove large tumors and perform amputations. Continuing his researches, he developed, in 1885, a method of injecting the drug into the vertebral canal between the spinous processes where it "should become absorbed by the minute plexuses of veins and so carried to the cord." Quite recently, Professor Bier, of Kiel, has advanced one step in this practice and deposited a solution of cocain within the subarachnoid space. His example was speedily followed by Oberst, Seldovitch and other European surgeons, and, above all, by Tuffier. This practice is now extending to the United States and other countries. Various reports have been published, narrating its successful application in major operations involving the lower extremities, genital organs and abdominal cavity. Anesthesia ensues within five to ten minutes
Evidence of histamine-induced myocardial ischaemia: reversal by chlorpheniramine and potentiation by atherosclerosis
Authors: C A TOZZI, S G DORRELL, G F MERRILL
Journal: Cardiovascular Research (1985)

The effects of histamine on coronary vasomotor tone and on myocardial blood flow distribution were studied in the anaesthetised rabbit in the absence of histamine H1-receptor blockade and calcium channel blockade. Two groups of rabbits were used, those fed a normal diet and those fed a high cholesterol diet (2%) for 8 to 12 weeks. Continuous recordings of standard limb lead electrocardiograms (ECG) were obtained, and all animals were pretreated with cimetidine, an H2-receptor blocker, to minimise the intervening systemic effects of histamine. In the absence of H1-receptor blockade, histamine produced a marked (40 to 50%) reduction in coronary blood flow without significantly affecting other cardiovascular variables. This effect was seen uniformly across the free wall of the left ventricle, ie endo-epi flow ratios did not significantly change. Concomitant with the coronary vasoconstriction were significant depressions (greater than or equal to 0.1 mV) of the ECG ST-segment and elevation of cardiac tissue lactate and lactate:pyruvate ratio. These histamine-mediated responses were independently abolished by chlorpheniramine (1.5 mg X kg-1 iv) and verapamil (0.5 mg X kg-1 iv). Atherosclerosis reduced the average dose of histamine needed to induce these ischaemic changes from 55 +/- 6 to 34 +/- 6 micrograms X kg-1 X min-1 (p less than 0.05). These findings suggest that in the H2-receptor blocked rabbit coronary vascular bed histamine causes tissue ischaemia by an H1-receptor mechanism. The decrement in myocardial blood flow appears to involve activation of plasma membrane calcium channels and is sensitive to atherosclerosis.
Myringotomy in Acute Otitis Media
Authors: Oliver F. Roddey
Journal: JAMA (1966)

One hundred and eighty-one children with primary attacks of acute, purulent otitis media with bulging tympanic membranes were treated with antibiotics and nasal decongestants, and in approximately one half of the patients selected by random method, myringotomies were also performed. The only significant difference between the two groups, as judged by resolution of the middle-ear pathology, audiometry, and clinical response, was greater pain relief in a small group in whom there had been severe earache initially. Myringotomies were performed on patients in each group when resolution of the middle-ear pathology failed to occur within a reasonable length of time.
Modification of abnormal left ventricular diastolic properties by nifedipine in patients with hypertrophic cardiomyopathy.
Authors: B H Lorell, W J Paulus, W Grossman, J Wynne, P F Cohn
Journal: Circulation (1982)

The effect of nifedipine on left ventricular isovolumic relaxation and diastolic filling properties and systemic and left ventricular hemodynamics was studied in 15 patients with hypertrophic cardiomyopathy. After nidefipine (10 mg sublingually), the prolonged left ventricular isovolumic relaxation time assessed by echocardiography decreased from 112 +/- 26 to 83 +/- 23 msec (p less than 0.0001), and the left ventricular pressure decay as measured by time constant T improved from 63 +/- 20 to 49 +/- 11 msec (p less than 0.05). Left ventricular filling dynamics also improved as assessed by a return toward normal in the depressed peak rate of left ventricular diastolic filling (dimension change 72 +/- 37 to 101 +/- 39 mm/sec, p less than 0.01) and the peak rate of posterior wall thinning (47 +/- 31 to 68 +/- 36 mm/sec, p less than 0.001). These changes were accompanied by hemodynamic evidence of improved diastolic function shown as a decrease in left ventricular end-diastolic pressure and a downward shift in the left ventricular diastolic pressure-dimension relationship, suggesting improved left ventricular distensibility. After nifedipine, there was a slight increase in heart rate and a decrease in systemic ventricular distensibility. After nifedipine, there was a slight increase in heart rate and a decrease in systemic arterial blood pressure, and no depression of the left ventricular percent fractional shortening or cardiac index. These data indicate that abnormal left ventricular relaxation and diastolic filling rates in hypertrophic cardiomyopathy are dynamic and favorably modified by nifedipine, and that this effect is not related to a depression of left ventricular systolic function.
Bone cells, sclerostin, and FGF23: what’s bred in the bone will come out in the flesh
Authors: Susan M. Ott
Journal: Kidney International (2015)

Bone metabolism is linked to systemic diseases, and new research shows that the bone cells have endocrine functions that affect multiple organs. They secrete sclerostin, FGF23, prostaglandins, and osteocalcin. Pereira et al. examined gene expression of cells grown from bone biopsies of adolescents with renal osteodystrophy, as a first step to understanding how the bone-cell abnormalities contribute to cardiovascular and metabolic problems in these patients.
Crystallographic changes in calcium phosphates during plasma-spraying
Authors: L.G. Ellies, D.G.A. Nelson, J.D.B. Featherstone
Journal: Biomaterials (1992)

Coating hydroxyapatite (HA) onto metal implant surfaces using the plasma-spraying technique has been investigated in several laboratories as a means of improving the mechanical properties of the bulk ceramic. This study describes crystallographic changes which can occur during the plasma-spraying of calcium phosphate powders. A precipitated calcium-deficient apatite and a high temperature near-stoichiometric HA were each sprayed onto metal substrates in an argon plasma using several hydrogen gas flow conditions at various temperatures. The surfaces were examined by X-ray diffraction and scanning electron microscopy. The plasma-sprayed products were identified as a mixture of calcium phosphates including HA, β-tricalcium phosphate (β-TCP) and calcium oxide. Stoichiometric HA when plasma-sprayed showed the least (5%) degradation. Since β-TCP is more resorbable than HA in vivo, varying the HAβ-TCP ratio on the plasma-sprayed surface may provide a method to control surface dissolution of the coating.
Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity
Authors: Aaron D. Schimmer, Kate Welsh, Clemencia Pinilla, Zhiliang Wang, Maryla Krajewska, Marie-Josee Bonneau, Irene M. Pedersen, Shinichi Kitada, Fiona L. Scott, Beatrice Bailly-Maitre, Gennadi Glinsky, Dominick Scudiero, Edward Sausville, Guy Salvesen, Adel Nefzi, John M. Ostresh, Richard A. Houghten, John C. Reed
Journal: Cancer Cell (2004)
Effect of a Community Intervention on Patient Delay and Emergency Medical Service Use in Acute Coronary Heart Disease
Authors: Russell V. Luepker, James M. Raczynski, Stravoula Osganian, Robert J. Goldberg, John R. Finnegan, Jr, Jerris R. Hedges, David C. Goff, Jr, Mickey S. Eisenberg, Jane G. Zapka, Henry A. Feldman, Darwin R. Labarthe, Paul G. McGovern, Carol E. Cornell, Michael A. Proschan, Denise G. Simons-Morton, None for the REACT Study Group
Journal: JAMA (2000)

ContextDelayed access to medical care in patients with acute myocardial infarction (AMI) is common and increases myocardial damage and mortality.ObjectiveTo evaluate a community intervention to reduce patient delay from symptom onset to hospital presentation and increase emergency medical service (EMS) use.Design and SettingThe Rapid Early Action for Coronary Treatment Trial, a randomized trial conducted from 1995 to 1997 in 20 US cities (10 matched pairs; population range, 55,777-238,912) in 10 states.ParticipantsA total of 59,944 adults aged 30 years or older presenting to hospital emergency departments (EDs) with chest pain, of whom 20,364 met the primary population criteria of suspected acute coronary heart disease on admission and were discharged with a coronary heart disease–related diagnosis.InterventionOne city in each pair was randomly assigned to an 18-month intervention that targeted mass media, community organizations, and professional, public, and patient education to increase appropriate patient actions for AMI symptoms (primary population, n=10,563). The other city in each pair was randomly assigned to reference status (primary population, n=9801).Main Outcome MeasuresTime from symptom onset to ED arrival and EMS use, compared between intervention and reference city pairs.ResultsGeneral population surveys provided evidence of increased public awareness and knowledge of program messages. Patient delay from symptom onset to hospital arrival at baseline (median, 140 minutes) was identical in the intervention and reference communities. Delay time decreased in intervention communities by −4.7% per year (95% confidence interval [CI], −8.6% to −0.6%), but the change did not differ significantly from that observed in reference communities (−6.8% per year; 95% CI, −14.5% to 1.6%; P=.54). EMS use by the primary study population increased significantly in intervention communities compared with reference communities, with a net effect of 20% (95% CI, 7%-34%; P&lt;.005). Total numbers of ED presentations for chest pain and patients with chest pain discharged from the ED, as well as EMS use among patients with chest pain released from the ED, did not change significantly.ConclusionsIn this study, despite an 18-month intervention, time from symptom onset to hospital arrival for patients with chest pain did not change differentially between groups, although increased appropriate EMS use occurred in intervention communities. New strategies are needed if delay time from symptom onset to hospital presentation is to be decreased further in patients with suspected AMI.
Does mycobacterium vaccae immunization to pregnant BALB/c mice alter cytokine levels in spleen cultures, bone marrow eosinophils, and lung histopathology in offsprings with chronic asthma model?
Authors: T. Akkoc, C. Ozdemir, O. Yesil, D. Yazi, N.N. Bahceciler, S. Ilgar, O. Peker, I.B. Barlan
Journal: Journal of Allergy and Clinical Immunology (2003)