tbuckley/cabot-search huggingface dataset:
Diverse Mechanisms of Myocardial p38 Mitogen-Activated Protein Kinase Activation
Authors: Masaya Tanno, Rekha Bassi, Diana A. Gorog, Adrian T. Saurin, Jie Jiang, Richard J. Heads, Jody L. Martin, Roger J. Davis, Richard A. Flavell, Michael S. Marber
Journal: Circulation Research (2003)

The ischemic activation of p38α mitogen-activated protein kinase (p38α-MAPK) is thought to contribute to myocardial injury. Under other circumstances, activation is through dual phosphorylation by MAPK kinase 3 (MKK3). Therefore, the mkk3 −/− murine heart should be protected during ischemia. In retrogradely perfused mkk3 −/− and mkk3 +/+ mouse hearts subjected to 30 minutes of global ischemia and 120 minutes of reperfusion, infarction/risk volume was similar (50±5 versus 51±4, P =0.93, respectively), as was intraischemic p38-MAPK phosphorylation (10 minutes ischemia as percent basal, 608±224 versus 384±104, P =0.43, respectively). This occurred despite undetectable activation of MKK3/6 in mkk3 −/− hearts. However, tumor necrosis factor (TNF)-induced p38-MAPK phosphorylation was markedly diminished in mkk3 −/− vs mkk3 +/+ hearts (percent basal, 127±23 versus 540±267, respectively, P =0.04), suggesting an MKK-independent activation mechanism by ischemia. Hence, we examined p38-MAPK activation by TAB1-associated autophosphorylation. In wild-type mice and mkk3 −/− mice, the p38-MAPK catalytic site inhibitor SB203580 (1 μmol/L) diminished phosphorylation during ischemia versus control (10 minutes ischemia as percent basal, 143±2 versus 436±96, P =0.003, and 122±25 versus 623±176, P =0.05, respectively) and reduced infarction volume (infarction/risk volume, 57±5 versus 36±3, P &lt;0.001, and 50±5 versus 29±3, P =0.003, respectively) but did not alter TNF-induced activation, although in homogenates of ischemic hearts but not TNF-exposed hearts, p38-MAPK was associated with TAB1. Furthermore, adenovirally expressed wild-type and drug-resistant p38α-MAPK, lacking the SB203580 binding site, was phosphorylated when H9c2 myoblasts were subjected to simulated ischemia. However, SB203580 (1 μmol/L) did not prevent the phosphorylation of resistant p38α-MAPK. These findings suggest the ischemic activation of p38-MAPK contributing to myocardial injury is by TAB1-associated autophosphorylation.
Biology, Crime and Ethics: A Study of Biological Explanations for Criminal Behavior
Authors: TOKSOZ B. Karasu
Journal: JAMA (1985)

Drs Frank H. Marsh and Janet Katz bring us, in a single volume, a number of impressive papers, perspectives, and positions, previously and independently published in different journals and books. Apparently their primary mission is to demonstrate that reducing highly complex issues of crime into unidimensional (biologic) causation would have serious negative consequences. The book starts with a foreword by E. D. Pellegrino, MD, and the anthologists deliver what they promise in the introduction. The current resurgence of biologic explanations for human behavior has overreaching implications. Is criminality biochemically determined? Are we the instruments of our genes? What are the ethical dimensions and the responsibilities involved in attempting to alter the biochemical or genetic makeup of psychopaths? This volume attempts to answer these and other questions by presenting recent investigations on aggression and crime as well as the methods of controlling human behavior and by exploring their legal and ethical
Antidepressant Use in Patients Prescribed β-Blockers
Authors: W. C. Appel
Journal: JAMA (1986)

<h3>To the Editor.—</h3> The recent article by Avorn et al<sup>1</sup>on increased antidepressant use in patients taking β-blockers appears to be a "chicken-and-egg" problem when viewed from a perspective that is different from that of the authors. Their conclusion—"we consistently found a higher frequency of antidepressant use among patients prescribed β-blockers"—should be examined as to the validity of the reverse case: the frequency of β-blockers use among patients prescribed tricyclic antidepressants (TCAs). Since the overall frequency of use is greater for TCAs than for β-blockers in two age groups (20 to 44 and older than 65 years), can their use be attributed to β-blockers use? The finding that β-blocker use is greater than that of other antihypertensive drugs may simply confirm the results of the survey quoted by the authors, ie, that β-blockers are more frequently prescribed than other drugs. This may equally apply to hypertensives among a population
The Hyperelastic Joint Disease Syndrome
Authors: Richard C. Gardner
Journal: JAMA (1976)

<h3>To the Editor.—</h3> The hyperelastic joint disease syndrome is a commonly overlooked disorder. The clinical course of individuals affected by it is underemphasized, and the standard textbooks do not clearly define the condition. Although the disease is presumably of autosomal dominant inheritance and a disorder of collagen metabolism, patients who have it do<i>not</i>have hyperelastic skin or an abnormal mucopolysaccharide metabolism, as in hereditary connective tissue disorders. The syndrome may be a variant of either the Marfan or Ehlers-Danlos syndrome. Orthopedic complaints are found in a high percentage of individuals with hyperelastic joints. Many have a family history of hypermobility. Although some people with severe cases are contortionists, this is not a prerequisite for the diagnosis. The diagnosis is made when an individual can actively touch the flexor or extensor surface of his forearm with his thumb (a movement often associated with subluxation and hypermobility of other finger joints
Antibiotic Therapy of Bacterial Endocarditis
Authors: JOSEPH E. GERACI, WILLIAM J. MARTIN
Journal: Circulation (1954)

Thirty-three cases of enterococcal endocarditis encountered during the decade from January 1944 through December 1953 are reviewed. In vitro studies indicate that penicillin and streptomycin are the best antibiotic pair for bactericidal effect. Twelve of the last 14 patients were cured (86 per cent), 10 with combined therapy. The cure rate in enterococcal endocarditis now approximates that of endocarditis caused by penicillin-sensitive streptococci. A maximal number of cures is achieved by individualization of therapy. The daily dosage of penicillin and the duration of combined penicillin-streptomycin therapy should be guided by in vitro bactericidal tests employing the patient's strain of enterococcus.
THE RATIONAL TREATMENT OF TYPHOID FEVER.A paper read before the Ohio State Medical Society, at Cincinnati, May 5, 1892.
Authors: F. W. LANGDON
Journal: JAMA (1892)

Mr. President and Fellow-members of the Ohio State Medical Society: The subject of fever—in its general aspect—has been deemed worthy of so much labor and study on the part of the physiologist, the pathologist and the clinician, and is of such practical import to all who practice our art in any of its branches, that no apology is necessary, I trust, for bringing one of its numerous phases before this society for consideration. Looking at its most constant and evident symptom—the pyrexia—the physiologist points out, and the pathologist, and clinician confirm the probable •existence of heat-producing, heat controlling and heat dissipating areas, situated in the central nervous system, and influencing by their abnormal action the production of this particular symptom. That the pyrexia, however, does not constitute the disease is quite evident, since, it may be absent, controlled or even eliminated, and yet the patient be far from well. While,
Bicuspid Aortic Valve
Authors: Hector I. Michelena, Siddharth K. Prakash, Alessandro Della Corte, Malenka M. Bissell, Nandan Anavekar, Patrick Mathieu, Yohan Bossé, Giuseppe Limongelli, Eduardo Bossone, D.Woodrow Benson, Patrizio Lancellotti, Eric M. Isselbacher, Maurice Enriquez-Sarano, Thoralf M. Sundt, Philippe Pibarot, Artur Evangelista, Dianna M. Milewicz, Simon C. Body
Journal: Circulation (2014)
Transcatheter Aortic Valve Implantation
Authors: R. Gurvitch, D.A. Wood, E.L. Tay, J. Leipsic, J. Ye, S.V. Lichtenstein, C.R. Thompson, R.G. Carere, N. Wijesinghe, F. Nietlispach, R.H. Boone, S. Lauck, A. Cheung, J.G. Webb
Journal: Circulation (2010)

Background— Although short- and medium-term outcomes after transcatheter aortic valve implantation are encouraging, long-term data on valve function and clinical outcomes are limited. Methods and Results— Consecutive high-risk patients who had been declined as surgical candidates because of comorbidities but who underwent successful transcatheter aortic valve implantation with a balloon-expandable valve between January 2005 and December 2006 and survived past 30 days were assessed. Clinical, echocardiographic, and computed tomographic follow-up examinations were performed. Seventy patients who underwent successful procedures and survived longer than 30 days were evaluated at a minimum follow-up of 3 years. At a median follow-up of 3.7 years (interquartile range 3.4 to 4.3 years), survival was 57%. Survival at 1, 2, and 3 years was 81%, 74%, and 61%, respectively. Freedom from reoperation was 98.5% (1 patient with endocarditis). During this early procedural experience, 11 patients died within 30 days, and 8 procedures were unsuccessful. When these patients were included, overall survival was 51%. Transaortic pressure gradients increased from 10.0 mm Hg (interquartile range 8.0 to 12.0 mm Hg) immediately after the procedure to 12.1 mm Hg (interquartile range 8.6 to 16.0 mm Hg) after 3 years ( P =0.03). Bioprosthetic valve area decreased from a mean of 1.7±0.4 cm 2 after the procedure to 1.4±0.3 cm 2 after 3 years ( P &lt;0.01). Aortic incompetence after implantation was trivial or mild in 84% of cases and remained unchanged or improved over time. There were no cases of structural valvular deterioration, stent fracture, deformation, or valve migration. Conclusions— Transcatheter aortic valve implantation demonstrates good medium- to long-term durability and preserved hemodynamic function, with no evidence of structural failure. The procedure appears to offer an adequate and lasting resolution of aortic stenosis in selected patients.
Treatment of hypertension in the UK: simple as ABCD?
Authors: B. Williams
Journal: Journal of the Royal Society of Medicine (2003)

The measurement of blood pressure in primary care is a simple screening test to identify individuals at high risk of cardiovascular disease, including stroke. Hypertension is one of the most important preventable causes of premature morbidity and mortality1 and a recent analysis of combined epidemiological data indicates that the relation between blood pressure and cardiovascular disease is much steeper than previously thought;2 in other words, the potential benefits of intervention are higher. Allied to these impressive population data is a clinical-trials evidence base larger than any other in clinical medicine, pointing to the effectiveness of antihypertensive therapy in reducing cardiovascular risk.3 This evidence has provided the substrate for numerous guidelines on detection and treatment. The Chief Medical Officer for England has identified hypertension as one of his five priority areas, and the treatment of hypertension is a key target in National Service Frameworks for the prevention of coronary heart disease and stroke.
Androgens and growth.
Authors: P. H. Rayner
Journal: BMJ (1969)

M Jlu OURjAL old, and both she and her sister-in-law were clear that difficulty in swallowing was her main problem.The patient looked ill and wasted, and was admitted as an emergency, with a probable diagnosis of carcinoma of the oesophagus.Alternatively, it was considered that she may have had enlarged nodes compressing her oesophagus and .causing the dysphagia.In the ward she admitted to frequency, as she had been drinking a lot to try to wash her food down.She also had nocturia.Her pulse was regular at 92 and her blood pres- sure was 150/80.Apart from wasting there were no abnormal signs.A barium meal report stated, " the oesophagus showed no evidence of obstruction and had normal peri- staltic movements, but there is a slight irregularity of the margin extending through- out the whole length-?significance.The duodenal cap appeared normal.There is a
Monoamine Oxidase Inhibitors, Tyramine, and Cheese
Authors: David Horwitz, Walter Lovenberg, Karl Engelman, Albert Sjoerdsma
Journal: JAMA (1964)

Marked potentiation of the pressor effects of tyramine hydrochloride, given orally and intravenously, was demonstrated in patients receiving a monoamine oxidase (MAO) inhibitor. Assays of the tyramine content of various foods revealed up to 25μg/ml in wine and 1.4 mg/gm in some cheeses. As little as 20 gm of cheese produced pressor responses which were controllable with phentolamine methane-sulfonate in MAO-inhibited patients. These findings extend previous work on the mechanism of cheese toxicity and emphasize one of the hazards of treatment with MAO inhibitors.
Book: Tomorrow's Cures Today? How to Reform the Health Research System
Authors: F. Q Wood
Journal: BMJ (2001)

Donald R Forsdyke Harwood Academic Publishers, £26, pp 186 ISBN 90 5702 6031 Rating: ![Graphic][1]</img>![Graphic][2]</img> Have major cures been delayed for political and personal reasons rather than because of the state of scientific knowledge or the availability of funds? Do those who make important scientific advances always receive adequate recognition? Which areas of research is the “quick fix” mentality driving and which researchers are deemed worthy of funding support? Are scientists forced to engage in unethical practices to ensure continuity of funding? Does the race for funds risk alienating young and talented scientists from the research enterprise? These are some of the questions … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
Hemodynamic and antifibrotic effects of losartan in rats with liver fibrosis and/or portal hypertension
Authors: Vincent Croquet, Frédéric Moal, Nary Veal, Jianhua Wang, Frédéric Oberti, Jérôme Roux, Eric Vuillemin, Yves Gallois, Olivier Douay, Daniel Chappard, Paul Calès
Journal: Journal of Hepatology (2002)
Clinical Lecture on Erysipelas: Its Nature and Affinities
Authors: W. S. Savory
Journal: BMJ (1873)

You may remember that, durino the prevalence of erysipelas last winter several cases occurred in the hospital.For awhile, indeed, the disease may be said to have been epidemic here-on a very small scale, to be sure, but still large enough to yield some useful lessons.In one ward, Abernethy, between the middle of January and the beginning of March, five patients were attacked.There were of course many points of in- terest in this outbreak of the affection under our very eyes; an excel- lent opportunity was aff-orded for the study of it.And of these points I wish now to fix your attention especially upon two-those two which were illustrated by the cases in Abernethy, and by some of you very often discussed.The first of these is that, of the patients in the ward, those only who had wounds were affected-the subjects of diseases not accompanied by an open wound escaping; and that the first local sign of the disease-the blush of redness-almost always appeared at the margin of the wound.The second is that the disease, beyond question, spread by contagion; the fresh cases not appearing indifferently in any part of the ward, but the disease passing, in almost every in- stance, from the person affected to the patient nearest to him who had an open wound.Now, as you know very well, neither of these facts is new.Each of them, even when viewed singly, is full of import.ance ; but how vastly is their significance augmented when considered together; what a light is thrown by each upon the other!How con- tradictory, too, at the first glance, they seem of each other !I remem- ber that they struck several of you thus, and led to many questions.Let us consider one of them.Is erysipelas a specific fever, or is it a local disease ?There are high authorities and much argument for either view.It may be said, perhaps, that the generally accepted view is, that erysipelas is a specific fever-alliea, therefore, to scarlatina, measles, and small-pox.This is the doctrine set forth, for example, by the highest authorities in our standard works ; but there are many eminent men who maintain the doctrine that erysipelas is simply a local disease.For examples of this view I may refer you to Mr. Higginbottom, in the BRITISH MEDICAL J-OURNAL for June 7th, I865, P. i ; also to an article in the same paper for June i8th, T870, p. 632.Now the two facts, so marked in our cases to which I have alluded, seem, I say, at the first glance, to be diametrically opposed to each other on this great question.Did not the commencement of the disease about a wound
Surveillance of the Safety of Oral Poliomyelitis Vaccine in England and Wales 1962--4
Authors: D. L. Miller, N. S. Galbraith
Journal: BMJ (1965)

When, in 1956, inactivated poliomyelitis (Salk) vaccine became available for routine immunization in England and Wales the Ministry of Health set up a scheme of poliomyelitis surveillance. The objects were to provide a means of rapid detection pf pos sible outbreaks of vaccine-induced poliomyelitis, such as occurred in the United States owing to the presence of incompletely inactivated virus in a batch of vaccine (Nathanson and Langmuir, 1963), and to observe the efficacy of the vaccine. The results were reported by Geffen and Spicer (1960), Geffen (1960), and Roden (1964), and though a number of vaccine associated cases occurred they concluded that the vaccine was both safe and effective.
Preconditioning with recombinant high-mobility group box 1 protein protects the kidney against ischemia–reperfusion injury in mice
Authors: Huiling Wu, Renske Steenstra, Elianne C.S. de Boer, Cathy Y. Zhao, Jin Ma, Jorieke M. van der Stelt, Steven J. Chadban
Journal: Kidney International (2013)
Dipterex teratogenicity in the rat, hamster, and mouse when given by gavage.
Authors: R E Staples, E H Goulding
Journal: Environmental Health Perspectives (1979)

Dipterex was teratogenic after administration by gavage (t.i.d.) at a dose level of 480 mg/kg-day to the CP rat on days 6 through 15 of gestation, but not when administered only on days 8 or 10 of gestation. A positive teratogenic response also occurred in the hamster after administration on days 7 through 11 of gestation at 400 mg/kg-day; the apparent no-effect level for the criteria studied was 200 mg/kg-day. Embryotoxicity, but not teratogenicity, occurred after administration of 400 mg/kg-day on day 8 of gestation. In both species, the teratogenicity seen was not merely due to reduced maternal food consumption during the period of exposure. The mouse was less susceptible to Dipterex than were the rat and hamster, but a significant increase in the incidence of cleft palates resulted from exposure on days 10 through 14, or on days 12 through 14 of gestation.
MicroRNA-101, Down-regulated in Hepatocellular Carcinoma, Promotes Apoptosis and Suppresses Tumorigenicity
Authors: Hang Su, Jian-Rong Yang, Teng Xu, Jun Huang, Li Xu, Yunfei Yuan, Shi-Mei Zhuang
Journal: Cancer Research (2009)

Abstract Although aberrant microRNA (miRNA) expressions have been observed in different types of cancer, their pathophysiologic role and their relevance to tumorigenesis are still largely unknown. In this study, we first evaluated the expression of 308 miRNAs in human hepatocellular carcinoma (HCC) and normal hepatic tissues and identified 29 differentially expressed miRNAs in HCC tissues. miR-101, a significantly down-regulated miRNA, was further studied in greater detail because the signal pathway(s) regulated by miR-101 and the role of miR-101 in tumorigenesis have not yet been elucidated. Interestingly, decreased expression of miR-101 was found in all six hepatoma cell lines examined and in as high as 94.1% of HCC tissues, compared with their nontumor counterparts. Furthermore, ectopic expression of miR-101 dramatically suppressed the ability of hepatoma cells to form colonies in vitro and to develop tumors in nude mice. We also found that miR-101 could sensitize hepatoma cell lines to both serum starvation– and chemotherapeutic drug–induced apoptosis. Further investigation revealed that miR-101 significantly repressed the expression of luciferase carrying the 3′-untranslated region of Mcl-1 and reduced the endogenous protein level of Mcl-1, whereas the miR-101 inhibitor obviously up-regulated Mcl-1 expression and inhibited cell apoptosis. Moreover, silencing of Mcl-1 phenocopied the effect of miR-101 and forced expression of Mcl-1 could reverse the proapoptotic effect of miR-101. These results indicate that miR-101 may exert its proapoptotic function via targeting Mcl-1. Taken together, our data suggest an important role of miR-101 in the molecular etiology of cancer and implicate the potential application of miR-101 in cancer therapy. [Cancer Res 2009;69(3):1135–42]
Response to methotrexate in fibrosing alveolitis associated with connective tissue disease.
Authors: D G Scott, P A Bacon
Journal: Thorax (1980)

Methotrexate by intermittent intramuscular injection was used to treat three patients with fibrosing alveolitis complicating connective tissue diseases. All three patients had improvement of symptoms, two had radiological improvement, and one had significant improvement of pulmonary function. Two patients whose pulmonary symptoms, function, and chest radiographs had deteriorated on penicillamine improved when treated with methotrexate. Methotrexate may be a useful treatment for fibrosing alveolitis complicating connective tissue diseases.
Transcranial Magnetic Stimulation in the Reversal of Motor Conversion Disorder
Authors: Carlos Schönfeldt-Lecuona, Bernhard J. Connemann, Manfred Spitzer, Uwe Herwig
Journal: Psychotherapy and Psychosomatics (2003)

&lt;i&gt;Background:&lt;/i&gt; There is no agreement on the most effective therapy for motor conversion symptoms. Functional electric stimulation has been successfully used to reverse conversion paralysis. We tested the therapeutic potential of high-frequency repetitive transcranial magnetic stimulation (rTMS) in a 20-year-old patient suffering from a conversion paralysis of the right arm. &lt;i&gt;Method:&lt;/i&gt; rTMS was applied to the contralateral motor cortex. Stimulations were performed on working days at a frequency of 15 Hz (train length 2 s; inter-train interval 4 s) yielding 4,000 pulses/day. &lt;i&gt;Results:&lt;/i&gt; Within 12 weeks, motor function, hyposensibility and muscle bulk were completely restored. &lt;i&gt;Conclusions:&lt;/i&gt; The patient recovered completely during rTMS treatment. In addition to possible psychological effects, rTMS may have had a causal therapeutic effect by strengthening corticocortical connections and thereby priming voluntary movements. Further controlled studies are needed.