tbuckley/cabot-search huggingface dataset:
Abstract 3494: Experimentally validated modeling for optimizing therapeutic combinations of oncolytic adenoviruses and MEK inhibitor
Authors: Marisa Shiina, Neda Bagheri, Douglas Lauffenburger, Wolfgang Michael Korn
Journal: Cancer Research (2010)

Abstract Oncolytic adenoviruses are therapeutic anti-cancer agents that selectively replicate in and lyse cancer cells motivating their use in targeted gene therapy. Successful entry of adenoviruses into target cells depends on attachment of the adenovirus fiber-knob protein to the Coxsackie-and Adenovirus Receptor (CAR), which is often down-regulated in highly malignant cells. In a previous study, we demonstrate that MEK inhibition may counter this effect by up-regulating CAR expression. In this study we optimize infection by investigating the combinatorial effect of oncolytic adenovirus infection and MEK inhibition through data-driven models and model-driven experiments. To motivate and test our hypotheses, we use HCT116 colon cancer cell line treated with MEK inhibitor, CI1040, and infected with oncolytic adenoviruses, ONYX-015, Delta-24 and Delta-24RGD. We developed a nonlinear ordinary differential equation model that characterizes the dynamics of these cancer cells subject to ONYX-015 infection modulated by CI1040. Resulting simulations offer predictions that may help guide experimental design and inform optimal timing of CI1040 treatment and ONYX-015 infection to minimize cancer growth. Experimental results demonstrate that HCT116 cells treated with CI1040 for 2 days and infected with adenoviruses have stronger cytopathic effects, greater virus uptake, and greater production when compared to the DMSO control. We also found that G1 cell cycle arrest, caused by CI1040 treatment, is associated with increased virus production. To assess the role of release from cell cycle arrest as a mechanism leading to enhanced production of oncolytic adenoviruses, we synchronize cells by density arrest for 48 hours, release and infect with adenoviruses. The results showed a more potent cell killing effect and virus production on cells arrested in G1 and released. We expanded our analysis to a panel of 21 pancreatic cell lines, as this tumor type is a possible target for adenoviral therapies. Enhanced virus replication and cell killing were observed in different pancreatic cell lines, suggesting that combination therapy of CI1040 and oncolytic adenoviruses have potential implications for the design of future clinical trials and improved oncolytic adenoviruses therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3494.
Myonecrosis After Revascularization Procedures
Authors: Robert M. Califf, Alaa E. Abdelmeguid, Richard E. Kuntz, Jeffrey J. Popma, Charles J. Davidson, Eric A. Cohen, Neal S. Kleiman, Kenneth W. Mahaffey, Eric J. Topol, Carl J. Pepine, Ray J. Lipicky, Christopher B. Granger, Robert A. Harrington, Barbara E. Tardiff, Brian S. Crenshaw, Robert P. Bauman, Bram D. Zuckerman, Bernard R. Chaitman, John A. Bittl, E.Magnus Ohman
Journal: Journal of the American College of Cardiology (1998)
Excitation-contraction coupling in myocardium of nonhibernating and hibernating chipmunks: effects of isoprenaline, a high calcium medium, and ryanodine.
Authors: N Kondo
Journal: Circulation Research (1986)

The electromechanical responses to isoprenaline and a high calcium medium on cardiac muscles from nonhibernating and hibernating chipmunks were studied in the presence and the absence of ryanodine. In nonhibernating animal preparations, isoprenaline (5 X 10(-8) M) caused a marked positive inotropic effect with an increase in the amplitude of the action potential plateau and augmented the slow action potential in muscle depolarized with 26 mM K+. In hibernating animal preparations, isoprenaline failed to cause a positive inotropic effect in spite of an increase in the amplitude of action potential plateau and slow action potentials. Similar inotropic effects were caused in the two preparations when extracellular calcium was raised to 6 mM, but action potential plateau and slow action potentials of the two preparations were less affected by this procedure; only in nonhibernating animal preparations was the amplitude of the slow action potential slightly increased. Ryanodine (2 X 10(-6) M) partially inhibited the contraction but augmented the action potential plateau and slow action potentials in nonhibernating animal preparations, while in hibernating animal preparations, it eliminated the contraction and severely inhibited the action potential plateau and slow action potentials. The electrical effects of isoprenaline on the two preparations and of a high calcium medium on nonhibernating animal preparations were more pronounced in the presence of ryanodine than in the absence of it. However, the electrical activity on hibernating animal preparations was unaffected by a high calcium medium in either the presence or absence of ryanodine.(ABSTRACT TRUNCATED AT 250 WORDS)
Bioethics in Industry Settings: One Situation Where a Code for Bioethicists Would Help
Authors: David Perlman
Journal: The American Journal of Bioethics (2005)

Click to increase image sizeClick to decrease image size ACKNOWLEDGEMENTS I am indebted to the thoughtful comments of my fellow panelists at the ASBH 2004 Annual Meeting and 2005 Spring Meeting—Gary Cohen, J.D. (Vice President, Ethics & Corporate Responsibility, Millennium Pharmaceuticals), Chris MacDonald, Ph.D. (Assistant Professor of Philosophy, Saint Mary's University), and Trisha Phillips, Ph.D. candidate at Rice University (Instructor, Mississippi State University)—and audience members at these presentations, especially Carl Elliott, M.D., Ph.D., and Françoise Baylis, Ph.D.
Haemophilus influenzae type b resistant to ampicillin and chloramphenicol.
Authors: M A Catry, M V Vaz Pato
Journal: BMJ (1983)

decades since Halsted until it was more or less forced on surgeons (and others) who treated the necessity of radical operation as an article of faith.Finally, Professor Dudley's statement: "It was deemed necessary to use a randomised trial" for streptomycin in tuber- culosis is not quite what he terms "a good historical example."If he is referring to the early British trial of streptomycin for meningeal tuberculosis, it is widely understood that that trial was forced on the investigators by a shortage of streptomycin.With these important exceptions Professor Dudley's paper remains a powerful thinkpiece which is, in spirit, an important contribution to any debate about appropriate clinical trials.
CD8+ cutaneous anaplastic large-cell lymphoma: report of two cases with immunophenotyping, T-cell-receptor gene rearrangement and electron microscopic studies
Authors: A. KIKUCHI, K. SAKURAOKA, S. KURIHARA, M. AKIYAMA, H. SHIMIZU, T. NISHIKAWA
Journal: British Journal of Dermatology (1992)

Journal Article CD8+ cutaneous anaplastic large‐cell lymphoma: report of two cases with immunophenotyping, T‐cell‐receptor gene rearrangement and electron microscopic studies Get access A. KIKUCHI, A. KIKUCHI Department of Dermatology, Saiseikai Yokomashi Nanbu Hospital, Yokohama, Kanagawa, Japan Dr A.Kikuchi, Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku‐ku, Tokyo 160, Japan. Search for other works by this author on: Oxford Academic Google Scholar K. SAKURAOKA, K. SAKURAOKA Department of Dermatology, Saiseikai Yokomashi Nanbu Hospital, Yokohama, Kanagawa, Japan Search for other works by this author on: Oxford Academic Google Scholar S. KURIHARA, S. KURIHARA Department of Dermatology, Saiseikai Yokomashi Nanbu Hospital, Yokohama, Kanagawa, Japan Search for other works by this author on: Oxford Academic Google Scholar M. AKIYAMA, M. AKIYAMA Department of Dermatology, Keio University School of Medicine, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar H. SHIMIZU, H. SHIMIZU Department of Dermatology, Keio University School of Medicine, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar T. NISHIKAWA T. NISHIKAWA Department of Dermatology, Keio University School of Medicine, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 126, Issue 4, 1 April 1992, Pages 404–408, https://doi.org/10.1111/j.1365-2133.1992.tb00690.x Published: 01 April 1992
Novel hepatoselective insulin analog: studies with a covalently linked thyroxyl-insulin complex in humans.
Authors: F Shojaee-Moradie, J K Powrie, E Sundermann, M W Spring, A Schüttler, P H Sönksen, D Brandenburg, R H Jones
Journal: Diabetes Care (2000)

OBJECTIVE: To test whether a thyroxyl-insulin analog with restricted access to receptor sites in peripheral tissues displays relative hepatoselectivity in humans. RESEARCH DESIGN AND METHODS: Five normal human subjects received a subcutaneous bolus injection of either N(alphaBl) L-thyroxyl-insulin (Bl-T4-Ins) or NPH insulin in random order. Insulin kinetics, relative effects on hepatic glucose production, and peripheral glucose uptake were studied using euglycemic clamp and stable isotope [D-6,6-(2)H2]glucose) dilution techniques. Blood samples were taken for the determination of total immunoreactive insulin/analog concentrations and for liquid chromatography to assess the protein binding of the analog in the circulation. RESULTS: After subcutaneous administration, Bl-T4-Ins was well tolerated and rapidly absorbed. The analog had a long serum half-life and was highly protein bound (approximately 86%). Its duration of action, as judged by the duration of infusion of exogenous glucose to maintain euglycemia, was similar to that of NPH insulin. The effect of the analogs on hepatic glucose production was similar to that of NPH insulin, indicating equivalent hepatic potency. The analog demonstrated less effect on peripheral glucose uptake than NPH insulin (P = 0.025), had no effect on metabolic clearance rate of glucose, and exhibited a reduced capacity to inhibit lipolysis (P &amp;lt; 0.05). CONCLUSIONS: When injected subcutaneously into normal human subjects, Bl-T4-Ins is well tolerated, quickly absorbed, and highly protein bound, resulting in a long plasma halflife. This analog appears to have a hepatoselective action, and, therefore, has the potential to provide more physiological insulin action than the insulin preparations currently used.
Effect of selective beta-adrenergic blockade and stimulation on regional myocardial blood flow following acute coronary artery occlusion in the awake dog
Authors: K. MELBY, R. J BACHE
Journal: Cardiovascular Research (1980)

This study was designed to evaluate the effects of alterations of β-receptor activity on intercoronary collateral blood flow after acute coronary artery occlusion in the awake dog. Blood flow following acute circumflex coronary occlusion was measured during: 1) control conditions; 2) selective β1-blockade with practolol; 3) combined β1 and β2 blockade with propranolol; and 4) selective β2 stimulation. Neither practolol nor propranolol significantly altered the volume or distribution of blood flow into the normally perfused or ischaemic myocardial areas, while β2 stimulation increased blood flow to the normally perfused myocardium from 1.13 ± 0.12 to 1.28 ± 0.10 cm3·min−1·g−1 (P <0.05). This increase in flow, which was directed preferentially to the subepicardium, was mediated by a significant decrease in coronary vascular resistance. In contrast to the effect on normally perfused myocardium, β2 stimulation resulted in a 47 ± 12% decrease in collateral flow into the central ischaemic zone (P <0.05), which was mediated by a combination of decreased arterial pressure and increased collateral vascular resistance during β2-agonist administration. Thus, although β2 stimulation produced a modest increase in blood flow to normally perfused myocardium, in the setting of acute myocardial ischaemia, β2 stimulation resulted in a significant decrease in intercoronary collateral flow.
A Cullin3-KLHL20 Ubiquitin Ligase-Dependent Pathway Targets PML to Potentiate HIF-1 Signaling and Prostate Cancer Progression
Authors: Wei-Chien Yuan, Yu-Ru Lee, Shiu-Feng Huang, Yu-Min Lin, Tzu-Yin Chen, Hsiang-Ching Chung, Chin-Hsien Tsai, Hsin-Yi Chen, Cheng-Ta Chiang, Chun-Kai Lai, Li-Ting Lu, Chun-Hau Chen, De-Leung Gu, Yeong-Shiau Pu, Yuh-Shan Jou, Kun Ping Lu, Pei-Wen Hsiao, Hsiu-Ming Shih, Ruey-Hwa Chen
Journal: Cancer Cell (2011)
Chronic Fenfluramine Administration: Some Cerebral Effects
Authors: S. A. Lewis, I. Oswald, D. L. F. Dunleavy
Journal: BMJ (1971)

Human cerebral function was monitored electrophysiologically during sleep over a period of months before, during, and after the intake of fenfluramine, 40-120 mg/day. Effects included dose-related reduction of paradoxical sleep, increase of intra-sleep restlessness, and changes in E.E.G. slow-wave sleep. It is hypothesized that weight loss may be associated with increase of the last. Grinding of teeth (bruxism) also was noted.Long-term studies make it possible to demonstrate changing central effects with time, including tolerance phenomena. Withdrawal abnormalities are related to the time taken for the drug to be eliminated-in the present case reaching a maximum four days after withdrawal.
Risk Factors in the Development of Coronary Heart Disease. Six Year Follow-up Experience—The Framingham Study.
Authors: W. B. Kannel
Journal: Annals of Internal Medicine (1961)

s1 May 1961Risk Factors in the Development of Coronary Heart Disease. Six Year Follow-up Experience—The Framingham Study.W. B. Kannel, M.D., (Assoc.), T. R. Dawber, M.D., F.A.C.P., A. Kagan, M.D., F.A.C.P., N. Revotskie, M.D., J. Stokes III, M.D., (Assoc.)W. B. Kannel, M.D., (Assoc.), T. R. Dawber, M.D., F.A.C.P., A. Kagan, M.D., F.A.C.P., N. Revotskie, M.D., J. Stokes III, M.D., (Assoc.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-54-5-1035_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFactors possibly related to the development of coronary heart disease were studied prospectively in a sample (ages 30-59) of a town's population. One hundred eighty-six individuals (125 men and 61 women) developed manifestations of coronary heart disease (36.3 per 1,000) during six years' observation following the initial examination of the 5,127 subjects initially free of such manifestations.In the age range of 30-44, there were 34 cases, with a male: female incidence ratio of 13-1; in the age range 45-62 the ratio in 152 cases decreased to approximately 2:1.Men had more serious diseases than women but incidence rates for... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPreventive Cardiology and Risk Assessment: Beyond LDLEnvironmental and Other Risk Indicators in the Aetiology of Cardiovascular and Cerebrovascular Disease 1 May 1961Volume 54, Issue 5Page: 1035-1035KeywordsCoronary heart diseaseMedical risk factors ePublished: 1 December 2008 Issue Published: 1 May 1961 PDF downloadLoading ...
P912 OUTCOME AFTER LIVER TRANSPLANTATION IN TWENTY-TWO PATIENTS WITH ISCHEMIC-LIKE CHOLANGIOPATHY WITH SECONDARY SCLEROSING CHOLANGITIS
Authors: G.I. Kirchner, A.P. Barreiros, M.N. Scherer, S. Farkas, B. Sinner, B. Salzberger, H.-J. Schlitt, M. Loss
Journal: Journal of Hepatology (2014)
FURTHER EXPERIENCE WITH COUMARIN ANTICOAGULANTS
Authors: Royal Rotter
Journal: JAMA (1952)

Bishydroxycoumarin (dicumarol®), cyclocumarol* ("cumopyran"), and ethyl biscoumacetate (tromexan®) are 4-hydroxycoumarin derivatives that have been used as anticoagulants in the treatment of thromboembolic diseases. Their therapeutic action depends on depression of the prothrombin activity of the blood, and frequent prothrombin determinations are necessary for their adequate control. Our aim has been to find a safe anticoagulant that is prompt in its therapeutic action and that produces hypoprothrombinemia of such regularity and similar degree that the frequency of prothrombin determinations could be lessened. A comparison of the chemical formulas of these three compounds was shown in the papers of Barker, Hanson, and Mann<sup>1</sup>and Shapiro.<sup>2</sup>The similarity was apparent from the presence of the 4-hydroxycoumarin radical in each. Cyclocumarol is about 1/100 as soluble in water as bishydroxycoumarin, while ethyl biscoumacetate is more soluble than bishydroxycoumarin. On a milligram per kilogram of body weight basis, cyclocumarol is about
Hydrogen ion infusion for treating severe metabolic alkalosis.
Authors: S E Williams
Journal: BMJ (1976)

observed an appreciable increase in serum cholesterol at the end of several weeks whereas we measured a serum cholesterol level three times as high as theirs at the end of three-and-a-half years.Pop- ulation studies,4 furthermore, clearly show the close correlation betwveen serum cholesterol and the prevalence of ischaemic heart disease.
Renal function and renin secretion after administration of ouabain and ouabain plus furosemide in conscious sheep.
Authors: E H Blaine, M B Zimmerman
Journal: Circulation Research (1978)

The effects of ouabain or ouabain and furosemide on renal function and renin secretion were studied in conscious isovolemic sheep. The sheep received a continuous renal arterial infusion of papaverine, 7 mg/min, throughout the experiment. Ouabain alone (7 X 10(-7) M in the renal plasma) produced significant decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) but not in renal perfusion pressure. Plasma [K+] rose after ouabain administration. Fractional (FENa) and absolute (UNaV) Na+ excretion were 2.9 +/- 1.0% (mean +/- SE) and 78 +/- 54 muEq/min, respectively, during the papaverine infusion and rose to 19 +/- 5.1% (P less than 0.05) and 528 +/- 116 muEq/min (P less than 0.01) after ouabain administration. Despite the large changes in Na+ reabsorption, renin secretion was not stimulated. During the control period, renin secretion was 281 +/- 131 ng/min and the average renin secretion after ouabain administration was 310 +/- 78 ng/min (not significant). A smaller dose of ouabain (2 X 10(-7) M) infused into the renal artery with 40 mg of furosemide, iv, did not decrease GFR but RPF was suppressed. FENa and UNaV averaged 4.4 +/- 1.6% and 121 +/- 44 muEq/min, respectively, while papaverine was infused into the renal artery and increased to 18 +/- 4.8% (P less than 0.05) and 636 +/- 209 muEq/min (P less than 0.05) after ouabain and furosemide were infused. Renin secretion was 118 +/- 62 ng/min during the control period and averaged 240 +/- 67 ng/min after ouabain plus furosemide. The difference was not statistically significant. Thus ouabain alone does not stimulate renin secretion in the conscious, isovolemic sheep despite a presumed increase in [NaCl] at the macula densa and inhibition of NaCl transport by the loop of Henle. Ouabain also blocks the normal stimulatory effects of furosemide on renin secretion.
Unusual Rectal Injury
Authors: A. G. Butters
Journal: BMJ (1955)

estimate of proportion of errors has a fairly large sampling error.The expectations depend on the expansion of the bi- nomial (p+q)n, where p is the probability of obtaining a false result.Table III shows the reliability of the test withTABLE III Error if all Animals Repeat rate No. of Rats Used Give Same Result (One or More Animals Giving Divergent Results) 2 1 in 173 1 in 7-6 3 ,,2,250 1 ,,5 4 1,, 29,450 1 ,,4 5 1, 400,300 1, 33increasing numbers of animals if all the animals give either positive or negative results.In a high proportion of cases the answer will not be clear-cut in the sense that one or more animals give divergent results.In these cases a repeat test would be required and the repeat rate has also been calculated.For most purposes a " two-rat " test would combine a sufficient degree of accuracy with a relatively low repeat rate.If a rapid answer is needed four rats should be used (Table IV).If all agree the chances of error are negligible, TABLE IV No. of Chances of Repeat Rate (Two or Rats Result Error More Animals Giving Used Divergent Results) 2 AB l in I 0 3 AAB ,,70 0 4 AAAB 1,, 5,536 1 in 32 5 AAAAB I ,42,750 1, 19and if one disagrees the chances of error for the remaining three are still only 1 in 5,500.The 3 to 1 ratio will occur with tolerable frequency, and only very few tests will have to be repeated.This approach allows a more critical test when clinical urgency or importance warrants the added expense. SummaryThe rat ovarian hyperaemia test was carried out on 282 samples of urine.When one rat per test was used a slightly greater number of correct positive findings were obtained than with the Hogben test, but the rat test gave a considerable number of false-positive results.The single-rat test is unsuitable for clinical purposes.By increasing the number of test animals, however, any desired degree of accuracy can be obtained.I wish to express my thanks to Dr. J. A.
Pediatric Clinical Gastroenterology
Authors: Mervin Silverberg
Journal: JAMA (1976)

<b>Gastrointestinal Problems in the Infant,</b>by Joyce Gryboski, 811 pp, 193 illus, $30, Canada $31.80, Philadelphia, Saunders, 1975. Prior to 1971, there were no publications devoted exclusively to pediatric gastroenterology. In the latter half of 1975, both the above texts appeared and have indeed demonstrated that this specialty has come of age. The second edition of<i>Pediatric Clinical Gastroenterology</i>has been significantly expanded to include such recent developments as new entities (eg, hepatitis B, α-1 antitrypsin, and secretory diarrheas); new procedures (eg, rectal manometry and fiberoptic endoscopy); and new therapies (eg, ostomy care and the Kasai operation for biliary atresia). There is a uniform attempt to explore pathogenic mechanisms, with little sacrifice of the main goal of practicality and immediate usefulness. The clinician is given a clear introduction to the role of bile acids in health and disease, with highlights woven throughout the text in the areas of digestion, diarrhea,
Disseminating Innovations in Health Care
Authors: Donald M. Berwick
Journal: JAMA (2003)

Health care is rich in evidence-based innovations, yet even when such innovations are implemented successfully in one location, they often disseminate slowly-if at all. Diffusion of innovations is a major challenge in all industries including health care. This article examines the theory and research on the dissemination of innovations and suggests applications of that theory to health care. It explores in detail 3 clusters of influence on the rate of diffusion of innovations within an organization: the perceptions of the innovation, the characteristics of the individuals who may adopt the change, and contextual and managerial factors within the organization. This theory makes plausible at least 7 recommendations for health care executives who want to accelerate the rate of diffusion of innovations within their organizations: find sound innovations, find and support "innovators," invest in "early adopters," make early adopter activity observable, trust and enable reinvention, create slack for change, and lead by example.