tbuckley/cabot-search huggingface dataset:
Multigene expression from a replicating adenovirus using native viral promoters
Authors: Maxine Bauzon, Daniel Castro, Michael Karr, Lynda K Hawkins, Terry W Hermiston
Journal: Molecular Therapy (2003)

We have developed a novel therapeutic gene delivery system for oncolytic adenoviruses that takes advantage of the endogenous gene expression machinery (promoters, splicing, polyadenylation signals) of the E3 transcription unit for gene delivery. In this work, we use two sites in the E3 region (6.7 K/gp19K and ADP sites) to demonstrate that (1) multiple therapeutic genes (MCP-3, TNFalpha) can be expressed from a single replicating Ad, (2) timing of expression of these therapeutic genes mimics that of the E3 region genes they replaced, (3) expression of the remaining genes in the complex E3 transcription unit is maintained, and (4) the multigene-expressing virus retains replication competence and ability to induce classical adenovirus cytopathic effects that parallel those of the parental adenovirus (ONYX-320). This system conserves the DNA packaging capacity of the size-constrained viral genome for therapeutic genes and can potentially be used to link therapeutic transgene expression to tumor-restricted viral replication. Potential clinical implications are discussed.
Echocardiographic estimation of pulmonary artery pressure in transposition of the great arteries.
Authors: H P Gutgesell
Journal: Circulation (1978)

To determine their usefulness in estimating pulmonary artery pressure, left ventricular systolic time intervals (STI) were determined by echocardiography in 65 patients with dextro-transposition of the great arteries (TGA). The STI were measured from recordings of pulmonary valve motion at 100 mm/sec paper speed. The pre-ejection period (PEP) and the ratio of PEP to left ventricular ejection time (PEP/LVET) were directly related to pulmonary artery pressure. The strongest correlations were that between PEP/LVET and pulmonary artery diastolic pressure (r = 0.70) and that between PEP/LVET and the ratio of mean pulmonary pressure to mean systemic pressure (r = 0.71). A value of PEP/LVET of less than 0.26 was consistently associated with pulmonary artery diastolic pressures of less than 20 mm Hg and, in 28 of 31 patients, pulmonary artery pressure less than one-third of mean systemic arterial pressure. Pulmonary hypertension was present in 18 of 22 patients with PEP/LVET of 0.30 or greater; elevated PEP/LVET was also present in four patients with abnormalities of cardiac rhythm or conduction, two of whom also had angiographic evidence of myocardial dysfunction.
Insulin Receptor Activation in Deletion 11q Chronic Lymphocytic Leukemia
Authors: Jennifer R. Brown
Journal: Clinical Cancer Research (2011)

Abstract The chromosomal abnormalities characteristic of chronic lymphocytic leukemia (CLL) are well studied, but the mechanisms underlying their contribution to pathogenesis are only partially elucidated. Integrated genomic profiling, focused on deletion 11q, has identified elevated expression of the insulin receptor in a subgroup of CLLs and associated it with worse outcomes. Clin Cancer Res; 17(9); 2605–7. ©2011 AACR.
DNA rearrangement and constitutive expression of the interleukin 6 gene in a mouse plasmacytoma.
Authors: T Blankenstein, Z H Qin, W Q Li, T Diamantstein
Journal: The Journal of Experimental Medicine (1990)

To study the potential involvement of IL-6 in the development of plasmacytomas, a number of plasmacytoma lines were analyzed for alterations in the IL-6 locus. A DNA rearrangement due to the insertion of an intracisternal A particle retrotransposon 18 bp 5' of the transcriptional start site was detected in the cell line MPC11. The IL-6 gene is constitutively expressed in MPC11, suggesting the involvement of IL-6 in the development of certain myeloma/plasmacytomas according to the "autocrine growth hypothesis".
TCT-614 Detailed Morphologic Characterization of the Strut Composition Following Absorb Scaffold Placement in a Porcine Coronary Artery Model Through 48 Months
Authors: Fumiyuki Otsuka, Erica Pacheco, LAURA E. Perkins, Kenichi Sakakura, Kazuyuki Yahagi, Elena Ladich, Frank D. Kolodgie, Richard Rapoza, Michael Joner, Renu Virmani
Journal: Journal of the American College of Cardiology (2014)
Systemic Lupus Erythematosus Syndrome Induced by Practolol
Authors: E. B. Raftery, A. M. Denman
Journal: BMJ (1973)

Three patients with angina pectoris treated with practolol in varying doses developed a syndrome of arthralgia, particularly of the small joints of the hands, rash, fever, a raised E.S.R., and positive tests for lupus erythematosus (L.E.) cells and antinuclear antibody. The syndrome responded partly to withdrawal of the drug, but steroids were required to produce adequate symptomatic improvement. These disease features suggest that this is an example of drug-induced systemic lupus erythematosus (S.L.E.). The impaired ability of lymphocytes from these patients to transform in vitro indicates a testable hypothesis for the pathogenesis of the syndrome.
Plasminogen interacts with human platelets through two distinct mechanisms.
Authors: L A Miles, M H Ginsberg, J G White, E F Plow
Journal: Journal of Clinical Investigation (1986)

Glu-plasminogen, the native form of plasminogen, interacts in a specific and saturable manner with unstimulated human platelets, and the binding is enhanced fivefold by thrombin stimulation (Miles and Plow, 1985. J. Biol. Chem. 260:4303). This study characterizes the nature of the Glu-plasminogen binding sites by analyzing platelets deficient in selected proteins and functions. Platelets from patients with afibrinogenemia, Gray platelet syndrome, and the Cam Variant of thrombasthenia, a form of thrombasthenia with near normal levels of glycoprotein IIb/IIIa (GPIIb/IIIa), showed minimal augmentation of plasminogen binding to thrombin-stimulated platelets but normal binding to unstimulated platelets. This selective deficiency indicates that two distinct mechanisms are involved in the interaction of plasminogen with platelets. These abnormal platelets share a deficiency in fibrinogen. Surface expression of platelet fibrinogen, however, was not sufficient for enhanced plasminogen binding to stimulated platelets, and experiments with alpha-thrombin and gamma-thrombin indicated that fibrin formation on the platelet surface is necessary for the augmented plasminogen binding. Unstimulated and stimulated thrombasthenic platelets deficient in GPIIb/IIIa bound markedly reduced levels of plasminogen, which suggests a role for GPIIb/IIIa in plasminogen binding to unstimulated platelets. Treatment of platelets to dissociate the heterodimeric complex of GPIIb/IIIa did not significantly perturb plasminogen binding to unstimulated platelets, but the complex may be necessary for thrombin-stimulated plasminogen binding via its interaction with platelet fibrin.
Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 Improves Stress and Rest Myocardial Perfusion Abnormalities in Patients With Severe Symptomatic Chronic Coronary Artery Disease
Authors: James E. Udelson, Vasken Dilsizian, Roger J. Laham, Nicolas Chronos, John Vansant, Michel Blais, James R. Galt, Marilyn Pike, Carl Yoshizawa, Michael Simons
Journal: Circulation (2000)

Background —We report the effects of the administration of recombinant fibroblast growth factor-2 (rFGF-2) protein on myocardial perfusion using single photon emission computed tomography imaging in humans with advanced coronary disease. Methods and Results —A total of 59 patients with coronary disease that was not amenable to mechanical revascularization underwent intracoronary (n=45) or intravenous (n=14) administration of rFGF-2 in ascending doses. Changes in perfusion were evaluated at baseline and again at 29, 57, and 180 days after rFGF-2 administration. In this uncontrolled study, perfusion scans were analyzed by 2 observers who were blinded to patient identity and test sequence; scans were displayed in random order, with scans from nonstudy patients randomly interspersed to enhance blinding. Combining all dose groups, a reduction occurred in the per-segment reversibility score (reflecting the magnitude of inducible ischemia) from 1.7±0.4 at baseline to 1.1±0.6 at day 29 ( P &lt;0.001), 1.2±0.7 at day 57 ( P &lt;0.001), and 1.1±0.7 at day 180 ( P &lt;0.001). The 37 patients with evidence of resting hypoperfusion had evidence of improved resting perfusion: their per-segment rest perfusion score of 1.5±0.5 at baseline decreased to 1.0±0.8 at day 29 ( P &lt;0.001), 1.0±0.8 at day 57 ( P =0.003), and 1.1±0.9 at day 180 ( P =0.11). Conclusions —These preliminary data suggest that the administration of rFGF-2 to patients with advanced coronary disease resulted in an attenuation of stress-induced ischemia and an improvement in resting myocardial perfusion; these findings are consistent with a favorable effect of therapeutic angiogenesis.
Insulin Angina
Authors: AARON E. PARSONNET
Journal: Annals of Internal Medicine (1931)

Article1 April 1931Insulin AnginaThe Development of the Stenocardial Syndrome Following the Administration of Insulin in Diabetics with Coronary ThrombosisAARON E. PARSONNET, M.D., ALBERT S. HYMAN, M.D.AARON E. PARSONNET, M.D., ALBERT S. HYMAN, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-10-1247 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptProbably no remedy in the past generation has received as much attention from every conceivable angle as has that of insulin. Since its introduction by Banting, Mc-Leod and Best in 1923, the entire treatment of diabetes mellitus has revolved around indications, contraindications, dosage and numerous other phases of insulin administration. In the six-year period from 1923 to 1929 there are listed in the Quarterly Cumulative Index Medicus more than 1,000 articles concerned with insulin therapy. It is, therefore, inevitable that in the chaotic wake following the introduction of methods of such a decidedly revolutionary scope that many conflicting views and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: AARON E. PARSONNET, M.D.; ALBERT S. HYMAN, M.D. Nextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byIntensive glucose control and hypoglycaemia: a new cardiovascular risk factor?Intensive Insulin Therapy in the Intensive Care Unit, Hypoglycemia, and Cardiovascular MortalityGlucagon: Prehospital therapy for hypoglycemiaHypokalaemia Occurring During Insulin-induced HypoglycaemiaThe effect of hypoglycemia on myocardial ischemic injury during acute experimental coronary artery occlusion.The mechanism of arrhythmias during insulin-induced hypoglycemiaAction of hypoglycemia on coronary insufficiency and mechanism of ECG alterationsTHE ASSOCIATION BETWEEN HYPOGLYCÆMIA AND MYOCARDIAL INFARCTIONA creed for the treatment of diabetesÜber die Entstehung des HerzinfarktsPancreatic extract (enzyme-free) in the treatment of diabetic and arteriosclerotic gangreneCARDIOVASCULAR CHANGES ASSOCIATED WITH THE INSULIN SHOCK TREATMENT*EMANUEL MESSINGER, A.B., M.D.Insulin-glucose therapy in heart diseaseTHE NUTRITION OF THE HEART IN RELATION TO THE ELECTROCARDIOGRAM AND ANGINAL PAINDie arterielle Blutversorgung des Herzens und ihre StörungenELECTROCARDIOGRAPHIC CHANGES DURING TREATMENT OF SEVERE DIABETES.Pathogenese und Prognose des Coma diabeticum 1 April 1931Volume 4, Issue 10Page: 1247-1256KeywordsAnginaDiabetes mellitusInsulin ePublished: 1 December 2008 Issue Published: 1 April 1931 PDF downloadLoading ...
Epigenetic modification enzymes: catalytic mechanisms and inhibitors
Authors: Duo Lu
Journal: Acta Pharmaceutica Sinica B (2013)

Epigenetic modifications alter chromatin structures and consequently affect transcription and cellular functions. Major epigenetic markers include DNA methylation and histone acetylation and methylation. The modifications are reversible and are achieved in aid of relative enzymes. Much effort has been directed at the understanding of the chemical mechanisms of individual catalytic reactions, which can serve as a foundation for inhibitor development. Among the many methods deployed, structural studies have proven the most effective for understanding enzyme-mediated modifications and have provided support for the development of lead-candidate drug inhibitors. This review briefly summarizes the existing knowledge on the catalytic mechanisms of the major epigenetic modification enzymes, with an emphasis on the structural information and inhibitors of these enzymes.
Fatty acid‐binding protein 4 and incident heart failure: the Cardiovascular Health Study
Authors: Luc Djoussé, Traci M. Bartz, Joachim H. Ix, Jinesh Kochar, Jorge R. Kizer, John S. Gottdiener, Russell P. Tracy, Dariush Mozaffarian, David S. Siscovick, Kenneth J. Mukamal, Susan J. Zieman
Journal: European Journal of Heart Failure (2012)
Progestin Regulation of Cellular Proliferation*
Authors: CHRISTINE L. CLARKE, ROBERT L. SUTHERLAND
Journal: Endocrine Reviews (1990)

THE control of cellular proliferation is known to involve a delicate balance between the effects of different regulatory molecules including hormones and growth factors which provide, in the immediate environment of the cell, signals to stimulate or inhibit cellular replication (1). The past decade has seen significant progress in the identification and characterization of novel regulatory molecules, generally referred to as growth factors, and definition of their molecular mechanisms of action (2, 3). With the recent emphasis on peptide growth factors it is perhaps less well appreciated that some of the largest physiological changes (both positive and negative) in rates of growth and cell proliferation are mediated by steroid hormones. Recent studies on breast cancer cells (4) and immature rat uterus (5, 6), illustrating estrogenic control of autocrine and paracrine growth factor production, support the view that some of these steroid-induced responses are intimately linked to growth factor-mediated pathways although debate continues as to whether the growth factor response is the cause, or the consequence, of the estrogenic effect on cellular proliferation (7, 8). Generally speaking, the molecular mechanisms by which steroid hormones control proliferation are not well defined, with the most developed knowledge being in the area of estrogen action where a number of recent reviews are available (4, 9–11).
Misdiagnosis and delayed diagnosis in traumatic intracranial haematoma.
Authors: S Galbraith
Journal: BMJ (1976)

Out of 51 patients with traumatic intracranial haematoma admitted to a teaching hospital 11 (22%) died undiagnosed, and out of 307 such patients transferred to the West of Scotland Regional Neurosurgical Centre 111 (36%) had been deteriorating for more than 12 hours in another hospital. In two-thirds of these cases the delay was due to an erroneous diagnosis, either of cerebrovascular accident or of alcoholic intoxication.
Sweet's Syndrome in Patients with MDS and<i>MEFV</i>Mutations
Authors: Tatsuro Jo, Kensuke Horio, Kiyoshi Migita
Journal: New England Journal of Medicine (2015)

Two patients with the myelodysplastic syndrome (MDS) presented with symptoms associated with familial Mediterranean fever. Sweet's syndrome also developed in the two patients, who were found to have mutations in the gene associated with familial Mediterranean fever.
Obstetric audit in general practice.
Authors: G N Marsh
Journal: BMJ (1977)

Many recent papers have tried to show how inadvisable it is for general practitioners to undertake obstetric care and more especially obstetric deliveries.1-3 The high proportion of artificially induced labours, the enthusiasm for the increasing mechanisation of labour, descriptions of unexpected and sinister disease that the inexperienced obstetrician would not detect have all made general practitioners less confident in obstetrics. By virtue of the very breadth of their specialty GPs find it difficult to aggregate sufficient numbers of cases to refute the allegations of mediocrity made about their obstetric care and the possibly poor obstetric outcome achieved by them. I will describe the results of the obstetric care in a practice that works closely with a specialist unit, and they are far superior to national averages. With the development of effectively functioning primary health care teams, increasingly containing vocationally trained general practitioner obstetricians, en couragement of this style of obstetric care could improve the overall national statistics. We believe that modern obstetrics should aim at normal pregnancy, labour, delivery, puerperium, and a healthy mother and breast-fed baby. Care should take place in a setting that the mother, after consulting her obstetrician, be he general practitioner or specialist, believes to be in the best interests of herself and her baby, not only physically but also socially and psychologically. When patient participation is becoming increasingly encouraged obstetrics above all specialties should be the one in which the mother's wishes and desires are met, as well as the rather narrower clinical dictums of the obstetrician himself.Future perinatal, neonatal, and maternal mortality and morbidity statistics will increasingly be viewed not in absolute terms but will be set against the amount of deviation from the normal process described above. Anderson, Turnbull, and Baird6 suggested that since the health of pregnant women was improving and the maternal age at first birth was falling, the need for obstetric interference should actually be getting less. We have attempted to implement that suggestion.
TREATMENT OF FACIAL ERYSIPELAS AT CAMP CODY, N. M.
Authors: ANTHONY A. AVATA
Journal: JAMA (1918)

Between Nov. 6, 1917, and May 15, 1918, 104 cases of erysipelas were treated at the base hospital at Camp Cody. Most of these began on the face. The disease followed drainage of the mastoid in seven cases, abscess of the scalp in three cases, demonstrable ulcer in the nose in three cases, hordeolum in one case, and burns of the face in one case. The remaining ninety cases were called "idiopathic." On certain occasions an influx of such cases was noted after a period of high winds and dust storms, such as characterize this place and favor the development of inflammations of the mucous membranes of the head generally. Although only one patient died as the result of erysipleas, the disease was responsible for a total of 2,497 hospital days, making it a matter of some importance to determine the best method of management and establishing it as a
Vitellogenin induction by xenobiotic estrogens in the red-eared turtle and African clawed frog.
Authors: B D Palmer, S K Palmer
Journal: Environmental Health Perspectives (1995)

Many environmental pollutants have estrogenic activity in animals. Xenobiotic estrogens include many pesticides and industrial chemicals that biocumulate. The impact of these common pollutants on the reproductive success of wildlife may be considerable, particularly in threatened or endangered species. This research examined the use of plasma vitellogenin in males as a biomarker for estrogenic xenobiotics in reptiles and amphibians. Adult male turtles (Trachemys scripta) and frogs (Xenopus laevis) were given ip injections of estradiol-17 beta (E2), diethylstilbestrol (DES), or o,p'-DDT (1-chloro-2-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl)benzene) daily for 7 days, and plasma was collected on day 14. The estrogenic activity of each compound was determined by measuring the induction of plasma vitellogenin. Vitellogenin was identified by precipitation, electrophoresis, Western blot, and enzyme-linked immunosorbant assay (ELISA). In both species, estradiol and DES treatments induced the most vitellogenin, whereas DDT treatments induced smaller amounts of vitellogenin in a dose-dependent fashion. These data indicate that induction of plasma vitellogenin in males may be a useful biomarker of xenobiotic estrogen activity in wild populations of reptiles and amphibians.
Bronchoconstriction occurring during exercise in asthmatic subjects.
Authors: K C Beck, K P Offord, P D Scanlon
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

To demonstrate physiologic changes associated with asthma symptoms that many patients with asthma develop during exercise, we used sustained constant-load and interval exercise protocols with subjects breathing dry room temperature air. In constant-load exercise, subjects pedaled a stationary bicycle at 50% of their maximal power capacity for 36 min. In interval protocols, subjects pedaled at 60% of maximal capacity for 6 min and then 40% of maximal for 6 min; the 12-min cycle was repeated three times for a total exercise time of 36 min. Maximal expiratory flow versus volume maneuvers (MEFV) were obtained before, at 6-min intervals during, and at 5-min intervals after exercise. Changes in peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV1), and forced expiratory flow at 50% of pre-exercise vital capacity (FEF50) were compared with pre-exercise values. Within 15 min after a maximal 1-min incremental exercise protocol, mean flows decreased compared with pre-exercise (PEF, mean -22%, range -46 to 5%; FEV1, mean -21%, range -42 to -3%; FEF50, mean -41%, range -80 to 3%; all p < 0.05). There were no significant changes in MEFV flows until 18 min of constant-load exercise, when FEV1 and FEF50 fell (FEV1, mean -6%, range -15 to 2%; FEF50, mean -14%, range -32 to 6%; both p < 0.05), although changes in PEF were minimal and were not significantly different compared with pre-exercise.(ABSTRACT TRUNCATED AT 250 WORDS)