tbuckley/cabot-search huggingface dataset:
Influences of anisotropic tissue structure on reentrant circuits in the epicardial border zone of subacute canine infarcts.
Authors: S M Dillon, M A Allessie, P C Ursell, A L Wit
Journal: Circulation Research (1988)

Excitation in the epicardial border zone of 3-5-day-old canine infarcts was mapped with an array of 192 bipolar electrodes during sustained ventricular tachycardia. Reentrant circuits were found in which activation occurred around long lines of apparent conduction block based on the criterion that excitation on opposite sides of the lines occurred with marked disparity in time. When the lines of apparent block were functional (i.e., occurred only during tachycardia and not during sinus rhythm or ventricular pacing) they were oriented parallel to the long axis of epicardial muscle fiber bundles. Isochrones distal to the lines were oriented parallel to them because widely separate sites within these isochrones were activated nearly simultaneously. This suggested that excitation not only occurred around the lines of block but also slowly across them. This slow activation occurred transverse to the long axis of the myocardial fibers and therefore might result because of the anisotropic tissue properties. To test this hypothesis, the epicardial border zone was stimulated during sinus rhythm through electrodes around its margin and at the center of the recording array. Activation transverse to the myocardial fibers in regions where lines of block occurred during tachycardia was slow, whereas it was rapid parallel to fibers' orientation. During tachycardia electrograms along the lines of apparent block had long durations and were fractionated, a characteristic that can also result from activation transverse to the myocardial fiber long axis. Therefore, we propose that the parallel orientation of the muscle bundles in the epicardial border zone is an important cause of ventricular tachycardia because activation transverse to myocardial fibers is sufficiently slow to permit the occurrence of reentry.
Human Neural Stem Cells Can Target and Deliver Therapeutic Genes to Breast Cancer Brain Metastases
Authors: Kyeung Min Joo, In H Park, Ji Y Shin, Juyoun Jin, Bong Gu Kang, Mi Hyun Kim, Se Jeong Lee, Mi-young Jo, Seung U Kim, Do-Hyun Nam
Journal: Molecular Therapy (2009)

The tumor-tropic properties of neural stem cells (NSCs) led to the development of a novel strategy for delivering therapeutic genes to tumors in the brain. To apply this strategy to the treatment of brain metastases, we made a human NSC line expressing cytosine deaminase (F3.CD), which converts 5-fluorocytosine (5-FC) into 5-fluorouracil, an anticancer agent. In vitro, the F3.CD cells significantly inhibited the growth of tumor cell lines in the presence of the prodrug 5-FC. In vivo, MDA-MB-435 human breast cancer cells were implanted into the brain of immune-deficient mouse stereotactically, and F3.CD cells were injected into the contralateral hemisphere followed by systemic 5-FC administration. The F3.CD cells migrated selectively into the brain metastases located in the opposite hemisphere and resulted in significantly reduced volumes. The F3.CD and 5-FC treatment also decreased both tumor volume and number of tumor mass significantly, when immune-deficient mouse had MDA-MB-435 cells injected into the internal carotid artery and F3.CD cells were transplanted into the contralateral brain hemisphere stereotactically. Taken together, brain transplantation of human NSCs, encoding the suicide enzyme CD, combined with systemic administration of the prodrug 5-FC, is an effective treatment regimen for brain metastases of tumors.
Autoimmune hemolytic anemia in an infant with giant cell hepatitis
Authors: Rajesh Kashyap, J.N. Sarangi, V.P. Choudhry
Journal: American Journal of Hematology (2006)

Autoimmune hemolytic anemia (AIHA) associated with giant cell hepatitis (GCH) is a rare disorder in infants. AIHA usually precedes the development of liver disease by months to years. Early recognition of the disease and prompt institution of immunosuppressive therapy results in clinical remission and prevents liver disease progression. Am. J. Hematol. 81:199–201, 2006. © 2006 Wiley-Liss, Inc.
Osborne and Craft duologue: relative values
Authors: D. Ward
Journal: Journal of the Royal Society of Medicine (2007)

In the letter we call on Reed to cease all involvement in arms fairs.In particular we state that Reed's involvement in the arms trade 'is entirely at odds with the ethical and social obligations we have to promote the beneficial applications of our work and prevent its misuse, to anticipate and evaluate the possible unintended consequences of scientific and technological developments, and to consider at all times the moral responsibility we carry for our work.'
A smartphone dongle for diagnosis of infectious diseases at the point of care
Authors: Tassaneewan Laksanasopin, Tiffany W. Guo, Samiksha Nayak, Archana A. Sridhara, Shi Xie, Owolabi O. Olowookere, Paolo Cadinu, Fanxing Meng, Natalie H. Chee, Jiyoon Kim, Curtis D. Chin, Elisaphane Munyazesa, Placidie Mugwaneza, Alex J. Rai, Veronicah Mugisha, Arnold R. Castro, David Steinmiller, Vincent Linder, Jessica E. Justman, Sabin Nsanzimana, Samuel K. Sia
Journal: Science Translational Medicine (2015)

A smartphone accessory can perform a point-of-care test that simultaneously detects three infectious disease markers from fingerprick whole blood in 15 min, as operated by health care workers trained on a software app.
Changes in subphase aggregates in rabbits injured by free fatty acid.
Authors: S B Hall, R W Hyde, R H Notter
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Rabbits treated with intravenous free fatty acid suffer an acute lung injury. Material obtained from these lungs by bronchoalveolar lavage (BAL) has dramatically impaired ability to lower surface tension in vitro despite normal levels of surfactant phospholipids. Although large quantities of surface-active inhibitors are present in BAL, their effects are not sufficient to explain the magnitude of surfactant inactivation. This study determines if alterations in the surfactant aggregates can explain the loss of surfactant function in fatty acid lung injury. In injured animals, the larger, most active surfactant particles recovered by centrifugal pelleting were found to be decreased in amount. The remaining large particles had reduced surface activity compared with control aggregates. In addition, large particles in injured animals had a higher density than control animals on sucrose gradients following equilibrium centrifugation. Interaction with serum components present in the injured BAL could explain these higher densities. The ability of the injured BAL to lower surface tension was improved by supplementation with normal levels of particles from injured lungs. Supplementation of injured BAL with control large aggregates improved activity further and restored the ability to lower surface tension to < 1 mN/m. Therefore both the decreased amount and activity of large surfactant aggregates in injured animals contributed significantly to the observed inactivation of surfactant. Diminished surfactant function from alteration in surfactant aggregates is a mechanism common to other forms of acute lung injury, and the design of therapies with exogenous surfactants in injured lungs will need to consider strategies that restore surfactant function towards normal.
Effects of Prolonging Peak Dobutamine Dose During Stress Echocardiography
Authors: Neil J Weissman, Geoffrey A Rose, Gary P Foster, Michael H Picard
Journal: Journal of the American College of Cardiology (1997)

Objectives. This study sought to test whether the physiologic advantage of a prolonged dobutamine stage during stress echocardiography can be effectively combined with a clinically practical infusion protocol. Background. Dobutamine has a half-life of 2 min and requires up to 10 min to achieve steady state. Despite these known pharmacodynamics, dobutamine stress echocardiography is routinely performed by advancing doses at 3-min intervals. Canine studies have shown that dobutamine stress echocardiography end points will occur at a lower dose if each stage is prolonged, but these findings have yet to be used in the clinical setting. Methods. The standard 3-min dobutamine dose stage during stress echocardiography was modified by extending the peak dose (40 μg/kg body weight per min) for an additional 2 min. Consecutive patients underwent this modified protocol to test whether the requirement for atropine could be reduced. According to this modified protocol, if a dobutamine stress echocardiographic end point (85% of maximal predicted heart rate, new wall motion abnormalities, hypotension, arrhythmia or intolerable symptoms) was not reached at 3 min of the peak dose, this dose was prolonged for an additional 2 min. If a dobutamine stress echocardiographic end point was still not attained, atropine (up to 1.0 mg intravenously) was administered. Results. The study included 84 patients, 22 of whom (26.2%) achieved a dobutamine stress echocardiographic end point using the standard 3-min stage. Of the 62 patients who did not reach an end point in the initial 3 min of peak dobutamine dose, the additional 2 min of dobutamine increased heart rate (from 99.6 ± 23.8 to 107.2 ± 23.2 beats/min, p < 0.01) and allowed 20 patients (32.3%, p < 0.01) to attain an end point. Of the remaining 42 patients, 23 never achieved a stress echocardiographic end point, despite 1.0 mg of atropine. One patient developed supraventricular tachycardia during the additional 2 min of dobutamine, and one developed nonsustained ventricular tachycardia after receiving atropine. Conclusions. These data demonstrate that a significant number of patients (32%) who do not reach a dobutamine stress echocardiographic end point with the standard protocol can safely attain an end point solely by extending the duration of the peak dose. Adoption of this strategy may reduce the need for supplemental atropine and its potential adverse effects. (J Am Coll Cardiol 1997;29:526–30)
A Phase 1, Dose-Escalation, Pharmacokinetic and Pharmacodynamic Study of BIIB021 Administered Orally in Patients with Advanced Solid Tumors
Authors: Muhammad Wasif Saif, Chris Takimoto, Monica Mita, Udai Banerji, Nicole Lamanna, Januario Castro, Susan O'Brien, Christopher Stogard, Daniel Von Hoff
Journal: Clinical Cancer Research (2013)

BIIB021 is the first oral, synthetic, non-geldanamycin-based HSP90 inhibitor that showed activity in preclinical models at low nanomolar concentrations. We performed a phase 1 trial of BIIB021 administered to subjects with advanced solid tumors.Sixty patients received BIIB021 capsules orally on days 1, 4, 8, 11, 15, and 18 of each course in schedule 1, and on days 1, 4, 8, 11, 15, 18, 22, and 25 of each course in schedule 2. The treatment schedules were repeated every 28 days. In addition to determining the MTD, we evaluated pharmacokinetics of BIIB021 and pharmacodynamic effects of BIIB021 [Hsp70, HER2 extracellular domain (HER2-ECD)].The MTD was 700 mg twice weekly when BIIB021 was dosed for 3 weeks out of each 4-week course. The MTD for continuous dosing regimen was established at 600 mg twice weekly. Gastrointestinal (nausea, vomiting), hot flashes, and neurologic (dizziness) events characterize the safety profile of BIIB021 dosed twice weekly, with events mostly mild or moderate. Plasma exposure to BIIB021 was dose-dependent. Cmax occurred at approximately 90 minutes and t1/2 was approximately 1 hour across dosing cohorts of 25 to 800 mg BIIB021 twice weekly. The biologic activity of BIIB021 was demonstrated in serum, PBMCs, and tumor tissue. Hsp70 levels were increased (>150% from baseline) and serum HER2-ECD was significantly decreased (>15% inhibition from baseline).BIIB021 twice weekly, given with or without the 1 of 4-week rest period was tolerated in subjects with advanced solid tumors at doses that are pharmacodynamically active.
Expressed emotions, early caregiver–child interaction, and disorders
Authors: Andreas Wiefel, Renate Schepker
Journal: Behavioral and Brain Sciences (2009)

Abstract In addition to the socio-relational framework of expressive behaviors (SRFB), we recommend integrating theoretical and empirical findings based on attachment theory. We advocate a dynamic interpretation of early caregiver–child interaction. The consequences of models from developmental psychology for the occurrence of psychopathology are demonstrated from a clinical perspective.
Tumor Necrosis Factor Induces Hemorrhagic Necrosis of a Sarcoma
Authors: Paul A. Robertson, Helen J. Ross, Robert A. Figlin
Journal: Annals of Internal Medicine (1989)

William B. Coley, MD, a surgeon of the early 20th century, noted the regression of a soft-tissue sarcoma in the neck of a patient after a life-threatening bacterial infection. He subsequently developed Coley toxins (sterilized cultures of various gram-negative bacilli), which he administered to patients with solid tumors to reproduce the antitumor effect he had observed with severe bacterial infections. The search for a pathophysiologic explanation of this phenomenon led Carswell and colleagues (1) in 1974 to describe tumor necrosis factor. This endotoxin-induced serum factor caused necrosis within 24 hours of subcutaneously transplanted methylcholanthrene A-induced sarcoma in BCG-primed mice. The
Rho-Associated Coiled-Coil-Containing Kinase 2 Deficiency in Bone Marrow–Derived Cells Leads to Increased Cholesterol Efflux and Decreased Atherosclerosis
Authors: Qian Zhou, Yu Mei, Takuhito Shoji, Xinbing Han, Karol Kaminski, Goo Taeg Oh, Pat P. Ongusaha, Kunzhong Zhang, Hannah Schmitt, Martin Moser, Christoph Bode, James K. Liao
Journal: Circulation (2012)

Background— Macrophages play a central role in the development of atherosclerosis. However, the signaling pathways that regulate their function are not well understood. The Rho-associated coiled-coil-containing kinases (ROCK1 and ROCK2) are serine-threonine protein kinases that are involved in the regulation of the actin cytoskeleton. Recent studies suggest that ROCK1 in macrophages and bone marrow–derived cells mediates atherogenesis. However, a similar role for ROCK2 in the pathogenesis of atherosclerosis has not been determined. Methods and Results— The bone marrows from wild-type, ROCK2 +/− , and ROCK2 −/− mice were transplanted into irradiated recipient low-density lipoprotein receptor −/− mice, and atherosclerosis was induced with a 16-week high-cholesterol diet. Compared with wild-type bone marrow–transplanted mice, ROCK2 +/− bone marrow–transplanted and ROCK2 −/− bone marrow–transplanted mice showed substantially less lipid accumulation in the aorta (8.46±1.42% and 9.80±2.34% versus 15.64±1.89%; P &lt;0.01 for both) and decreased atherosclerotic lesions in the subaortic sinus (158.1±44.4 and 330.1±109.5×10 3 μm 2 versus 520.2±125.7×10 3 μm 2 ; P &lt;0.01 for both). These findings correlated with decreased foam cell formation (2.27±0.57 versus 4.10±0.3; P &lt;0.01) and increased cholesterol efflux (17.65±0.6 versus 9.75±0.8; P &lt;0.05) in ROCK2-deficient mice that are mediated, in part, through the peroxisome proliferator-activated receptor-γ/liver X receptor/ATP-binding cassette transporter A1 pathway in macrophages. Conclusions— ROCK2 contributes to atherosclerosis, in part, by inhibiting peroxisome proliferator-activated receptor-γ–mediated reverse cholesterol transport in macrophages, which contributes to foam cell formation. These findings suggest that inhibition of ROCK2 in macrophages may have therapeutic benefits in preventing the development of atherosclerosis.
Identification of preoperative variables needed for risk adjustment of short-term mortality after coronary artery bypass graft surgery
Authors: Robert H. Jones, Edward L. Hannan, Karl E. Hammermeister, Elizabeth R. DeLong, Gerald T. O'Connor, Russell V. Luepker, Victor Parsonnet, David B. Pryor
Journal: Journal of the American College of Cardiology (1996)

The purpose of this consensus effort was to define and prioritize the importance of a set of clinical variables useful for monitoring and improving the short-term mortality of patients undergoing coronary artery bypass graft surgery (CABG).Despite widespread use of data bases to monitor the outcome of patients undergoing CABG, no consistent set of clinical variables has been defined for risk adjustment of observed outcomes for baseline differences in disease severity among patients.Experts with a background in epidemiology, biostatistics and clinical care with an interest in assessing outcomes of CABG derived from previous work with professional societies, government or academic institutions volunteered to participate in this unsponsored consensus process. Two meetings of this ad hoc working group were required to define and prioritize clinical variables into core, level 1 or level 2 groupings to reflect their importance for relating to short-term mortality after CABG. Definitions of these 44 variables were simple and specific to enhance objectivity of the 7 core, 13 level 1 and 24 level 2 variables. Core and level 1 variables were evaluated using data from five existing data bases, and core variables only were examined in an additional two data bases to confirm the consensus opinion of the relative prognostic power of each variable.Multivariable logistic regression models of the seven core variables showed all to be predictive of bypass surgery mortality in some of the seven existing data sets. Variables relating to acuteness, age and previous operation proved to be the most important in all data sets tested. Variables describing coronary anatomy appeared to be least significant. Models including both the 7 core and 13 level 1 variables in five of the seven data sets showed the core variables to reflect 45% to 83% of the predictive information. However, some level 1 variables were stronger than some core variables in some data sets.A relatively small number of clinical variables provide a large amount of prognostic information in patients undergoing CABG.
Increased <i>in vitro</i> cvsteinvl leukotriene release from blood leukocytes in patients with asthma, nasal polyps, and aspirin intolerance
Authors: T. Mewes, H. Riechelmann, L. Klimek
Journal: Allergy (1996)

In vitro cysteinyl leukotriene (cLT) release from blood leukocytes was measured in eight normal individuals (NI), nine patients with nasal polyps (NP) without aspirin intolerance, and eight patients with NP, asthma, and aspirin intolerance (AI). Blood leukocytes were prestimulated with interleukin‐3 (IL‐3) and incubated with acetylsalicylic acid (ASA) (10 and 100 pglml) together with C5a (10 ‐ ‐ 8 mol/l) for 18 h. cLT release (LTC 4 , LTD 4 and LTE 4 ) from blood leukocytes was measured with a competitive enzyme‐linked immunoassay. Background cLT release was 259±66 pg/ml (mean±æM) in the NI group, 185±33 pg/ml in the NP group, and 578±136 pg/ml in the A1 group (P = 0.1). After incubation with 10 μg/ml ASA, cLT concentration was lower in normal subjects (346±72 pg/ml) and in patients with NP (209±53) than in patients with A1 (686±75 pg/ml, P = 0.002). After incubation with 100 μg/ml ASA, cLT concentrations were 285±272 pg/ml in the NI group, 313±77 pg/ml in the NP group, and 654±121 pg/ml in the AI group (P = 0.04), respectively. Simultaneous incubation with ASA 10 μg/ml and C5a (10 ‐ ‐ 8 mol/l) resulted in a cLT concentration of 751±171 pg/ml in the NI group, 343±102 pg/ml in the NP group, and 2196±480 pg/ml in patients with A1 (P = 0.0006), whereas simultaneous incubation with ASA 100g/ml and C5a (10 ‐ ‐ 8 mol/l) resulted in 268±51 pg/ml in the NI group, 412±97 pg/ml in the NP group, and 1701±368 pg/ml in the AI group ( P= 0.005). In patients with AI, cLT release from blood leukocytes is altered when compared with normals and patients with NP. The presented cLT‐release assay could be of potential use in the in vitro diagnosis of AI.
Joan Lemkin (nee Casserley)
Authors: D Eyre-Walker
Journal: BMJ (2003)

Former clinical assistant in drug therapy St Mary's Hospital, Paddington (b Dunedin, New Zealand, 1928; q Otago University, Dunedin, 1952), died from bowel cancer on 7 June 2003.

Joan worked in Auckland and Wellington before coming to England. She obtained her FFARCS and worked at Queen Charlotte's and the Chelsea Hospital for Women, and then as registrar at Charing Cross. However, she had an attack of brucellosis and switched to psychiatry, obtaining her MRCPsych at the age of 55. For 20 years she worked at St Mary's, first in general psychiatry and then in drug therapy. Joan retained her love of New Zealand, returning annually for a holiday. She leaves a husband, James, and four children.
Abstract 146: The role of Mir-150 as a tumor suppressor in malignant lymphoma
Authors: Hiroyuki Tagawa, Atsushi Watanabe, Kenichi Sawada
Journal: Cancer Research (2011)

Abstract Disease specific genetic alteration or translocation have not been identified in NK/T cell lymphoma. We recently demonstrated that over expressions of miR-21 and/or miR-155 are frequently occurring in natural killer (NK) cell lymphoma/leukemia and deeply associated with their lymphomagenesis by deregulation of AKT signaling. In this study, we tried to identify tumor suppressor miRNA(s) in malignant lymphomas including B-cell, NK-cell and CD4+T-cell lymphoma, by using quantitative PCR and/or Northern blot analysis. We found that miR-150 in both cell lines and primary samples of NK and T-cell lymphoma showed significantly lower expression than those of normal natural killer cells and CD4+T cells. To examine the role for lymphomagenesis, we stably transduced miR-150 into lymphoma cell lines. Enforced expression of miR-150 in NK/T cell lymphoma cell lines showed increased levels of susceptibility of apoptosis, and showed senescence with reduced levels of telomerase activity and telomere DNA shortening. We further demonstrated that miR-150 directly down regulate AKT2, leading to reduced expression of phosphorylated AKTser473/474 with upregulation of tumor suppressors, Bim, p27 and p53. Since it has been proven that AKT kinase phosphorylate hTERT (human telomerase reverse transcript), downregulation of miR-150 in lymphomas lead to activate telomerase activity, resulting immortalization of the cancer cells. These results suggest that miR-150 play as a role of tumor suppressor in NK/T-cell lymphoma. Our recent and previous report demonstrate that downregulation of miR-150 and upregulation of miR-21/miR-155 collaborately contribute to NK/T-cell lymphomagenesis by deregulating AKT signaling. These findings will give a new insight into the pathogenesis of NK/T cell lymphoma and the miR-150 itself and/or AKT targeting therapy can be a useful against aggressive lymphoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 146. doi:10.1158/1538-7445.AM2011-146