tbuckley/cabot-search huggingface dataset:
Overexpression of FK-506–Binding Protein 12.0 Modulates Excitation–Contraction Coupling in Adult Rabbit Ventricular Cardiomyocytes
Authors: Tim Seidler, Christopher M. Loughrey, Darya Zibrova, Sarah Kettlewell, Nils Teucher, Harald Kögler, Gerd Hasenfuss, Godfrey L. Smith
Journal: Circulation Research (2007)

The effect of the 12-kDa isoform of FK-506-binding protein (FKBP)12.0 on cardiac excitation-contraction coupling was studied in adult rabbit ventricular myocytes after transfection with a recombinant adenovirus coding for human FKBP12.0 (Ad-FKBP12.0). Western blots confirmed overexpression (by 2.6+/-0.4 fold, n=5). FKBP12.0 association with rabbit cardiac ryanodine receptor (RyR2) was not detected by immunoprecipitation. However, glutathione S-transferase pull-down experiments indicated FKBP12.0-RyR2 binding to proteins isolated from human and rabbit but not dog myocardium. Voltage-clamp experiments indicated no effects of FKBP12.0 overexpression on L-type Ca2+ current (I(Ca,L)) or Ca2+ efflux rates via the Na+/Ca2+ exchanger. Ca2+ transient amplitude was also not significantly different. However, sarcoplasmic reticulum Ca2+ load was approximately 25% higher in myocytes in the Ad-FKBP12.0 group. The reduced ability of I(Ca,L) to initiate sarcoplasmic reticulum Ca2+ release was observed over a range of values of sarcoplasmic reticulum Ca2+ content, indicating that overexpression of FKBP12.0 reduces the sensitivity of RyR2 to Ca2+. Ca2+ spark morphology was measured in beta-escin-permeabilized cardiomyocytes. Ca2+ spark amplitude and duration were significantly increased, whereas frequency was decreased in cells overexpressing FKBP12.0. These changes were accompanied by an increased sarcoplasmic reticulum Ca2+ content. In summary, the effects of FKBP12.0 overexpression on intact and permeabilized cells were similar to those of tetracaine, a drug known to reduce RyR2 Ca2+ sensitivity and distinctly different from the effects of overexpression of the FKBP12.6 isomer. In conclusion, FKBP12.0-RyR2 interaction can regulate the gain of excitation-contraction coupling.
Imaging Electrocardiographic Dispersion of Depolarization and Repolarization During Ischemia
Authors: Martyn P. Nash, Chris P. Bradley, David J. Paterson
Journal: Circulation (2003)

Myocardial ischemia creates abnormal electrophysiological substrates that result in life-threatening ventricular arrhythmias. Identifying patients at risk of such abnormalities by use of body surface electrical measures is controversial. We investigated the sensitivity of torso measures, recorded simultaneously with epicardial electrograms, to changes in dispersion of depolarization and repolarization during localized ventricular ischemia.Ventricular epicardial electrograms were recorded from 5 anesthetized pigs with a 127-electrode sock. A controllable suture snare was used to ligate the left anterior descending coronary artery (LAD). The chest was reclosed, and a vest with 256 ECG electrodes was fitted to the torso. Simultaneous arrays of epicardial electrograms and torso ECGs were recorded during LAD occlusion and reperfusion. Activation-recovery intervals (ARIs), QTu and RTu dispersion (where u indicates upstroke), and QRST integrals were calculated, and these data were fitted to anatomically customized computational models of the swine ventricular epicardium and torso. LAD occlusion caused the epicardial ARI dispersion to steadily increase, whereas the location of shortest ARI shifted from the posterobasal ventricular tissue (control) to the anteroapical myocardium, distal to the suture snare. These changes were associated with a steady increase in the torso RTu dispersion as the shortest RTu interval moved from the right shoulder (control) to the sternum. QTu and RTu dispersion determined from the 12-lead ECG did not consistently reflect the myocardial changes.Although changes in myocardial repolarization dispersion resulting from localized ischemia are not reliably reflected in temporal indices derived from the 12-lead ECG, they can be readily identified with high-resolution torso ECG mapping.
PUVA treatment of psoriasis.
Authors: M Whitefield, H R Hudson, D Hyatt
Journal: BMJ (1978)

commented that in mental health we had our share of "loonies").This is precisely the technique used not infrequently in the Soviet Union, the technique which is rightly con- demned by the reviewer and Mr Levin.Models are factitious, giving delusions of reality, but lenses always give real views, albeit sometimes distorted or deflected.
Anterior uveitis as a complication of treatment with high dose cytosine‐arabinoside
Authors: David Planer, Tali Cukierman, Diana Liebster, Michael Ilsar, Tova Chajek‐Shaul
Journal: American Journal of Hematology (2004)

Abstract We present a case of a 21‐year‐old woman suffering from diffuse large B‐cell lymphoma who developed acute anterior uveitis shortly after completing chemotherapeutic course with HYPER‐CVAD protocol (cyclophosphamide, doxorubicin, vincristine, and dexamethasone) alternating with methotrexate and high‐dose cytosine‐arabinoside (HIDAC), with poor adherence to recommended prophylactic treatment with saline eye drops. Complete resolution of her symptoms was achieved within a few days of treatment with topical steroids. To our knowledge this is the first report of acute anterior uveitis secondary to treatment with HIDAC. Differential diagnosis and a suggested mechanism are discussed. Am. J. Hematol. 76:304–306, 2004. © 2004 Wiley‐Liss, Inc.
Skeletal Muscle Resting Membrane Potential in Potassium Deficiency
Authors: Gordon L. Bilbrey, Luis Herbin, Norman W. Carter, James P. Knochel
Journal: Journal of Clinical Investigation (1973)

The resting transmembrane potential of skeletal muscle (Em) is thought to be a function of the ratio of intracellular to extracellular potassium concentration ([Ki]/[Ko]). In potassium deficiency, the fall of [Ki] is proportionately less than the fall of [Ko], thus theoretically predicting a rise of Em. To examine this theory and to characterize Em in kaliopenic myopathy, muscle composition and Em were measured during moderate (n = 5) and severe (n = 11) K deficiency in the dog and compared with measurements in the severely K-deficient rat (n = 10). Mean measured Em rose during moderate K deficiency in four of five dogs (-85.4 to -94.6 mV) and during severe K deficiency in the rat (-89.1 to -94.9 mV). Both values closely approximated the increase in Em predicted by the Goldman equation. In contrast, during severe K deficiency in the dog, a significant decline (P < 0.001) of mean Em to -55 mV was observed.
On keeping an open mind
Authors: F. Godlee
Journal: BMJ (2011)

At some time or other, all of us will have fallen into the trap of “confirmation bias.” This is the tendency to favour information that confirms our view, regardless of whether the information is true. In medicine this can be dangerous, as Ron Berghmans shows in his Patient Journey (doi:10.1136/bmj.d5469). Suffering from back pain, he consulted his GP on several occasions over a period of months, to be told that there was nothing seriously wrong and denied (within the Dutch health system) referral to a specialist. Experiencing increasing pain and disability, he eventually referred himself to a neurologist outside the Netherlands, and was found to have extensive …
Moses Maimonides' Opposition to Astrology
Authors: Fred Rosner
Journal: JAMA (1976)

<h3>To the Editor.—</h3> In an editorial (235:1883, 1976), Samuel Vaisrub pleads for the medical profession to speak out against astrology. He points to the recently published statement by 186 leading scientists, including 18 Nobel laureates, denouncing astrology as a "pseudoscience that deludes and misguides." The generally prevalent belief in astrology during the Middle Ages was fully shared by the Jews, many of whom were convinced of the fundamental truth of the power of celestial bodies to influence human destiny. Moses Maimonides, the twelfth century rabbi, physician, philosopher, and astronomer, was strongly opposed to astrology. One of the few who not only dared raise his voice against this almost universally held belief, but even branded it as a superstition akin to idolatry, he unequivocally prohibited anyone to influence his actions by astrology, as an offense punishable by disciplinary flogging.<sup>1</sup> In his famous<i>Letter to Yemen</i>, Maimonides denounces astrology as a
An explanation for the reported observation that ATP dependent potassium channel openers fail to mimic preconditioning
Authors: G. J Grover
Journal: Cardiovascular Research (1993)

Journal Article An explanation for the reported observation that ATP dependent potassium channel openers fail to mimic preconditioning Get access Gary J Grover Gary J Grover Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA: G J Grover. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 9, September 1993, Page 1564, https://doi.org/10.1093/cvr/27.9.1564 Published: 01 September 1993
Use of a human plaque-forming cell assay to study peripheral blood bursa-equivalent cell activation and excessive suppressor cell activity in humoral immunodeficiency.
Authors: H G Herrod, R H Buckley
Journal: Journal of Clinical Investigation (1979)

A plaque assay that detects human mononuclear blood cells producing immunoglobulin (Ig)M antibody to sheep erythrocytes was investigated for its usefulness in studying B-cell activation and regulation in 24 patients with humoral immunodeficiency. Cells from 3 of 15 patients with common variable agammaglobulinemia produced some plaques (range 40--160/10(6) cells; normal range 80--1240/10(6)), but those from the other 12, from all 7 with x-linked agammaglobulinemia and from the 2 with x-linked immunodeficiency with hyper-IgM failed to produce any detectable plaques. In co-cultures of patient and normal cells a very good correlation was seen between results of the plaque assay and an IgM biosynthesis assay in detecting excessive suppressor cell activity. Cells from 7 of 15 common variable agammaglobulinemics, from 3 of 7 x-linked agammaglobulinemics, and from both patients with hyper-IgM caused significant suppression of IgM biosynthesis and(or) plaque formation by normal cells. The observations in the last two groups and discordance for excess suppressor activity in identical twins with common variable agammaglobulinemia suggest that the activity develops secondarily to whatever their primary defects may be. Culturing non-T cells from common variable agammaglobulinemics exhibiting excessive suppressor cell activity with normal T cells resulted in plaque formation in four of five patients so studied; in all five the suppressor activity was found in the T-cell population. The availability of a plaque assay for the study of blood cells from immunodeficient patients provides a new probe to examine the cellular nature of such defects.
Management of Malpositions of the Vertex
Authors: H. R. MacLennan
Journal: BMJ (1950)

With so much maternity work being done in hospitals there is to-day a tendency to study the various problems asso ciated with obstetrics solely from the statistical angle. Of course, much very useful information is gained by this approach ; but it can be cold and lifeless, and there are some problems which can be expressed in another way. It is not my intention to belittle the value of these statistical analyses, especially when, for all I know, there may be a Hogben sitting amongst us. I would prefer, however, to present the subject from the angle of the practitioner of obstetrics who is working on his own without the panoply of the hospital around him to share his burden and some times, to shield him from his failures. I would ratner talk of my experiences as an obstetrician doing private domi ciliary midwifery than as a consultant engaged in institu tional midwifery. By so doing we can meet on common ground and compare notes. During the past twenty years I have myself conducted a fair number of booked confinements : excluding emergency calls, there are over 2,500 which can be drawn upon. From such a number it is possible to form a judgment on what constitutes a difficult vertex presentation. In these cases I carried out my own antenatal work, and almost all the patients had a radiological examination at the thirty-sixth to thirty-seventh week. It was thus possible to select, with some accuracy, the cases of malposition of the vertex, and the malpositions which I here deal with are the occipito posterior position with the head lying in the oblique dia meter of the brim, the direct occipito-posterior with the head lying in the conjugate, and the occipito-lateral with the long axis of the head lying in the transverse diameter of the brim. Incidence
Junior doctors look forward to shorter hours
Authors: L. Beecham
Journal: BMJ (1998)

The European Commission has proposed that junior hospital doctors should be included in the directive on working time, which potentially limits their hours to an average of 48 a week.

If the Council of Ministers, which is due to meet on 2 December, endorses the proposal junior doctors would qualify for a rest period of 24 hours every week, 11 hours' consecutive rest each day, and …
Low back pain associated with internal snapping hip syndrome in a competitive cyclist
Authors: T L Little, J Mansoor
Journal: British Journal of Sports Medicine (2007)

Low back pain is a common complaint among cyclists. Here we present the case of a competitive master cyclist with low back pain and whose symptoms ultimately resolved when he was treated for internal snapping hip syndrome. Internal snapping hip syndrome is a painful lesion of the iliopsoas caused by snapping of the tendon over the iliopectineal eminence or anterior femoral head when the femur is extended from a flexed position. This is the first published report that we are aware of that describes this syndrome as a potential cause of low back pain in a competitive cyclist.
Brain's Diseases of the Nervous System
Authors: Frank R. Freemon
Journal: JAMA (1970)

A great textbook is often the product of one man. When that individual dies, the textbook may disappear into history. Bruce, for example, was unable to carry on the encyclopedic neurology text of Kinnier Wilson. At the age of 38 years, W. Russell Brain published the first edition of his Diseases of the Nervous System in 1933. From that year until 1962, as the author's name changed, English fashion, to Sir Russell Brain and then to Lord Brain of Eynsham, six editions of this work appeared. Brain's literary skill and scholarship pushed the volume to the forefront of neurology textbooks. In December 1966 when about half finished with revisions for the seventh edition, Lord Brain died. John N. Walton, an English neurologist with special interest in muscle disease, assumed the task of continuing Brain's textbook. He has clearly shown that a great text can survive its founder.  The seventh edition
Aerosol Gene Transfer With Inducible Nitric Oxide Synthase Reduces Hypoxic Pulmonary Hypertension and Pulmonary Vascular Remodeling in Rats
Authors: Werner Budts, Peter Pokreisz, Zengxuan Nong, Natascha Van Pelt, Hilde Gillijns, Robert Gerard, Rick Lyons, Desire Collen, Kenneth D. Bloch, Stefan Janssens
Journal: Circulation (2000)

Background —Nitric oxide (NO) is a potent vasodilator with an important role in the regulation of pulmonary vascular tone. The effects of NO synthase (NOS) gene transfer on pulmonary vascular remodeling associated with hypoxic pulmonary hypertension are unknown. Methods and Results —We aerosolized 3×10 9 pfu of an adenoviral vector containing inducible NOS gene (AdNOS2), constitutive NOS3 gene (AdNOS3), or no transgene (AdRR5) into rat lungs. Exhaled NO levels, monitored with chemiluminescence, were higher in AdNOS2-infected rats than in AdNOS3- and AdRR5-infected rats (at 3 days, 33±6 ppb, n=9, versus 17±4, n=9, and 6±2 ppb, n=3, P &lt;0.05 for both). Exposure to F io 2 0.10 for 7 days increased pulmonary artery pressure from 19±4 mm Hg (baseline) to 27±1 and 26±2 mm Hg in AdNOS3- and AdRR5-infected rats, respectively, but only to 21±1 mm Hg in AdNOS2-infected animals ( P &lt;0.05). After 7 days of hypoxia, total pulmonary resistance in AdRR5- and AdNOS3-infected rats was significantly higher than in AdNOS2-infected animals (0.41±0.05 and 0.39±0.07 versus 0.35±0.03 mm Hg · mL − 1 · min − 1 , respectively, P &lt;0.05). Right ventricular hypertrophy was reduced in AdNOS2-infected rats [right ventricular/(left ventricular+septal) weight, 0.19±0.10 versus 0.28±0.10 and 0.32±0.10 in AdRR5- and AdNOS3-infected rats, respectively, P &lt;0.05]. The percentage of muscularized precapillary pulmonary resistance vessels was also significantly decreased (18±4% versus 25±8% and 30±5% in AdRR5- and AdNOS3-infected rats, P &lt;0.05). Conclusions —Aerosol NOS2 gene transfer increases pulmonary NO production and significantly reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling. Aerosol NOS2 gene transfer may be a promising strategy to target pulmonary vascular disorders.
Scanning electron microscopy of the hepatocyte cytoskeleton in human liver tissue
Authors: Takeshi Okanoue, Masaharu Ohta, Kazutomo Kachi, Yoshiharu Ohta, Hikoharu Kanaoka, Yoshihiko Sawa, Keizo Kagawa, Tatsuro Takino, Samuel W. French
Journal: Journal of Hepatology (1988)
INHIBITION BY CERTAIN POLYSACCHARIDES OF HEMAGGLUTINATION AND OF MULTIPLICATION OF INFLUENZA VIRUS
Authors: R. H. Green, D. W. Woolley
Journal: The Journal of Experimental Medicine (1947)

The complex carbohydrates apple pectin, citrus pectin, flaxseed mucilage, blood group A substance, gum acacia, and gum myrrh as well as an extract of RBC, when examined in a pattern test, were shown to inhibit the agglutination of chicken RBC by influenza A virus. A number of other simple and complex carbohydrates showed no inhibitory effect. The hemagglutination-inhibiting action of apple pectin was examined in some detail and evidence was adduced to show that it affected both virus and red cell. Apple pectin was also found to inhibit the multiplication of influenza A virus in embryonated eggs.
THE EFFECT OF CYTOTOXIC AGENTS ON THE PRIMARY IMMUNE RESPONSE TO LISTERIA MONOCYTOGENES
Authors: S. P. Tripathy, G. B. Mackaness
Journal: The Journal of Experimental Medicine (1969)

Four drugs, representing four different categories of cytotoxic agents, were studied for their effect on the immune response to Listeria infection in mice. The development of the host's immune response is revealed by a progressive change in the slope of the bacterial growth curve in spleen and liver. It has its onset at 24 hr in untreated mice, but in the presence of effective immunosuppression the organism multiples uninterruptedly until the animal dies from overwhelming infection. When administered as single injections at the time of infection, cyclophosphamide, vinblastine, and azathioprine all produced an effective immunosuppression, characterized by continuous bacterial multiplication. Methotrexate was also immunosuppressive, but unlike the others its effects were reversible. They could be sustained, however, by further treatment. Studies of the time-response relationship indicated that cyclophosphamide was highly active over a broad time-span ranging from 2 days before infection to 4 days after infection. Vinblastine on the other hand was maximally active when given on the day of infection, while methotrexate had its greatest effect when given 48 hr after infection. These differences indicate that these three drugs act on different cell populations involved in the host's immune response. The effects observed have been discussed in relation to what is known of the modes of action of the drugs tested. An observation of interest was the phenomenon of enhanced immunity in animals treated with cyclophosphamide or vinblastine 7-11 days before, and with methotrexate 4 days before infection; reactive hyperplasia of lymphoid tissue following withdrawal of drug was again advanced as an explanation for the occurrence of this paradoxical effect. The experimental model employed is simple, requiring only routine bacteriological facilities and minimal equipment. It seems to offer a useful means of assessing the immunosuppressive activity of drugs and of determining the time-course of their action; it could also be of value in the screening of anticancer agents.
Stochastic nature and red cell population distribution of the sickling-induced Ca2+ permeability.
Authors: V L Lew, O E Ortiz, R M Bookchin
Journal: Journal of Clinical Investigation (1997)

To explore basic properties of the sickling-induced cation permeability pathway, the Ca2+ component (Psickle-Ca) was studied in density-fractionated sickle cell anemia (SS) discocytes through its effects on the activity of the cells' Ca2+sensitive K+-channels (KCa). The instant state of KCa channel activation was monitored during continuous or cyclic deoxygenation of the cells using a novel thiocyanate-densecell formation method. Each deoxy pulse caused a reversible, sustained Psickle-Ca, which activated KCa channels in only 10-45% of cells at physiological [Ca2+]o ("activated cells"). After removal of cells activated by each previous deoxy pulse, subsequent pulses generated similar activated cell fractions, indicating a random determination rather than the response of a specific vulnerable subpopulation. The fraction of activated cells rose monotonically with [Ca2+]o along a curve reflecting the cells' distribution of Psickle-Ca, with values high enough in a small cell fraction to trigger near-maximal KCa channels. Consistent with the stochastic nature of Psickle-Ca, repeated deoxygenated-oxygenated pulsing led to progressive dense cell formation, whereas single long pulses caused one early density shift. Thus deoxygenation-induced Ca2+-permeabilization in SS cells is a probabilistic event with large cumulative dehydrating potential. The possible molecular nature of Psickle-Ca is discussed.
Coronary Artery Bypass Procedures
Authors: David H. Spodick
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The editorial excerpt from Dr. Corday's address (<b>219</b>:507, 1972) casts a hard, cool factual light on the promising coronary artery bypass procedures. He has joined a growing band of skeptics (all, unfortunately, nonsurgeons) who are attempting to stem the stampede and one can endorse virtually his every point. Dr. Corday is one of the world's most distinguished cardiologists and his plea for a "national registry" cannot be ignored. Yet, I am astonished that nowhere in this thoughtful piece is there a hint of the desirability of controlled clinical trials. These are the most efficient method of getting honest (ie, minimally biased) results among truly comparable patients. A registry has merits insofar as bypass surgery will be pushed willy nilly by its enthusiasts (who formerly pushed Vineberg implants and other panaceas).<sup>1</sup>However, a registry will serve mainly to codify "trial and error," which is the traditional