tbuckley/cabot-search huggingface dataset:
Abstract 739: Targeting pancreatic cancers with a quadruplex-binding small molecule
Authors: Sonja Hampel, Mekala Gunaratnam, Maria de la Fuente, Andreas Schatzlein, Stephen Neidle
Journal: Cancer Research (2010)

Abstract We have previously reported on a novel series of tetra-aminoalkyl substituted naphthalene diimide compounds that bind to quadruplex nucleic acids and have high potency against a panel of human cancer cell lines. We now report on a further sub-set of derivatives with piperidino end-groups, which show high selectivity for human telomeric quadruplexes and only low-level binding to duplex DNA. These compounds are similarly potent in the cancer cell line panel, and also show potency against several pancreatic cancer cell lines, with typical IC50 values &amp;lt; 0.1μM. Telomerase activity is decreased in these cells on compound exposure, together with long-term growth arrest; this behaviour is consistent with a telomere targeting mechanism of action. These compounds also have &amp;gt; 40-fold selectivity over several normal fibroblast cell lines. We report on preliminary in vivo studies in this series, using the pancreatic cancer MiaPaCa-2 xenograft model. Starting doses for the compounds have been established in a dose ranging study. The compounds are relatively well-tolerated at doses well above the IC50 values, suggesting a sufficient therapeutic window exists to explore their therapeutic potential. The compounds show evidence of anticancer activity in the form of growth delay when established MiaPaCa-2 xenografts were dosed once daily by intraperitoneal injection. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 739.
"Growth" and the Diabetogenic Action of Anterior Pituitary Preparations
Authors: F. G. Young
Journal: BMJ (1941)

Joslin (1940) states that about 80% of his adult diabetic patients are, or have been, over weight at the time they come for treatment, and excessive weight is widely recognized as a frequent characteristic of the elderly diabetic patient.White-quoted by Joslin (1940) and by Coggeshall and
THE ARTERIAL BLOOD GASES, THE OXYGEN DISSOCIATION CURVE, AND THE ACID-BASE BALANCE IN POLYCYTHEMIA VERA 1
Authors: Donald E. Cassels, Minerva Morse
Journal: Journal of Clinical Investigation (1953)

Studies of the circulation and pulmonary func- tion in normal children and in patients with poly- cythemia related to cyanosis in congenital heart disease raised questions concerning the extent to which polycythemia itself might be responsible for some of the abnormalities observed in the blood in cyanotic congenital heart disease.These questions concerned the possibility that the in- creased viscosity of polycythemic blood might pre- vent proper diffusion of oxygen in the alveolar- capillary system, resulting in arterial oxygen un- saturation, the characteristics of the oxyhemo- globin dissociation curve in polycythemia vera, since this has been found shifted to the right in the blood of patients with cyanotic congenital heart disease (1), and the relation of a low CO2 content and combining power to polycythemia, since these were observed to be low in the sec- ondary polycythemia of congenital heart disease (2-4).Studies of the blood in polycythemia vera were made and compared with similar studies in cya- notic congenital heart disease.These included determinations of the oxygen content, oxygen capacity and oxygen saturation of arterial blood, the effect of breathing oxygen on the oxygen con- tent of such blood, the oxyhemoglobin dissociation curve and the carbon dioxide content, combining power and tension, and the pH. of arterial blood.It was hoped that some of these might be suffi- ciently characteristic to be helpful in differentiat- ing primary from secondary polycythemia.This report presents the data obtained during these studies.MATERIAL Blood from patients considered to have polycythemia vera was made available by the Department of Hema-
Rational Approach to the Surgical Management of Tricuspid Atresia
Authors: WILLIAM W. L. GLENN, THOMAS H. GARDNER, NORMAN S. TALNER, HORACE C. STANSEL, ICHIRO MATANO
Journal: Circulation (1968)

A rational approach to the surgical management of tricuspid atresia with diminished blood flow to the lungs is as follows: A cava-pulmonary artery shunt is performed as the initial operation whenever possible. In the newborn infant and in patients where the pulmonary artery is less than one-half the diameter of the superior vena cava where the two vessels cross, the right pulmonary artery is anastomosed end-to-side to the ascending aorta. Subsequently, when the right pulmonary artery has enlarged, it is detached from the aorta and anastomosed to the superior vena cava. Closure of the outflow from the right ventricle to the left lung can be expected in tricuspid atresia after the first year of life, and unless the ductus remains patent, a systemic artery-pulmonary artery shunt on the left side will be required to supplement the cava-pulmonary artery shunt. This shunt will also be required as a preliminary step to replacing the ascending aorta-right pulmonary artery shunt with a cava-right pulmonary artery shunt if blood flow to the left lung is by bronchial collateral arteries only. Banding of the pulmonary artery is indicated in those patients with excessive blood flow to the lungs. In the present series of 19 patients with tricuspid atresia, there were 17 with diminished flow to the lungs and two with excessive flow. Eight patients with small pulmonary arteries had a shunt made between the ascending aorta and right pulmonary artery. Five patients were less than two weeks of age. All survived operation; one died a year postoperatively of unknown causes. Two shunts have been replaced with cava-pulmonary artery shunts. Ten patients had a shunt made between the superior vena cava and the right pulmonary artery one to eight years ago. There has been no operative or late mortality. A supplemental systemic artery-pulmonary artery shunt on the left side has been established in three patients. Two patients have had operative enlargement of the interatrial communication. Excessive blood flow to the lungs was present in two patients. Neither patient survived banding of the pulmonary artery.
Tumor-Associated Macrophages and Survival in Classic Hodgkin's Lymphoma
Authors: Christian Steidl, Tang Lee, Sohrab P. Shah, Pedro Farinha, Guangming Han, Tarun Nayar, Allen Delaney, Steven J. Jones, Javeed Iqbal, Dennis D. Weisenburger, Martin A. Bast, Andreas Rosenwald, Hans-Konrad Muller-Hermelink, Lisa M. Rimsza, Elias Campo, Jan Delabie, Rita M. Braziel, James R. Cook, Ray R. Tubbs, Elaine S. Jaffe, Georg Lenz, Joseph M. Connors, Louis M. Staudt, Wing C. Chan, Randy D. Gascoyne
Journal: New England Journal of Medicine (2010)

Despite advances in treatments for Hodgkin's lymphoma, about 20% of patients still die from progressive disease. Current prognostic models predict the outcome of treatment with imperfect accuracy, and clinically relevant biomarkers have not been established to improve on the International Prognostic Score.Using gene-expression profiling, we analyzed 130 frozen samples obtained from patients with classic Hodgkin's lymphoma during diagnostic lymph-node biopsy to determine which cellular signatures were correlated with treatment outcome. We confirmed our findings in an independent cohort of 166 patients, using immunohistochemical analysis.Gene-expression profiling identified a gene signature of tumor-associated macrophages that was significantly associated with primary treatment failure (P=0.02). In an independent cohort of patients, we found that an increased number of CD68+ macrophages was correlated with a shortened progression-free survival (P=0.03) and with an increased likelihood of relapse after autologous hematopoietic stem-cell transplantation (P=0.008), resulting in shortened disease-specific survival (P=0.003). In multivariate analysis, this adverse prognostic factor outperformed the International Prognostic Score for disease-specific survival (P=0.003 vs. P=0.03). The absence of an elevated number of CD68+ cells in patients with limited-stage disease defined a subgroup of patients with a long-term disease-specific survival of 100% with the use of current treatment strategies.An increased number of tumor-associated macrophages was strongly associated with shortened survival in patients with classic Hodgkin's lymphoma and provides a new biomarker for risk stratification.
Gene Therapy: Carbon‐Dot‐Based Two‐Photon Visible Nanocarriers for Safe and Highly Efficient Delivery of siRNA and DNA (Adv. Healthcare Mater. 8/2014)
Authors: Liqin Wang, Xiaoyong Wang, Ashwinkumar Bhirde, Jianbo Cao, Yun Zeng, Xinglu Huang, Yaping Sun, Gang Liu, Xiaoyuan Chen
Journal: Advanced Healthcare Materials (2014)

X. Chen, G. Liu, and co-workers develop photoluminescent carbon dots (Cdot) by using low molecular weight amphiphilic polyethylenimine for surface passivation, which possesses low cytotoxicity, good stability, monodispersity with narrow size distribution, high gene delivery efficiency, and fluorescence performance. The Cdot formula introduced on page 1203 serves as a novel imaging-trackable gene-delivery na nocarrier promising for gene therapy and optical molecular imaging.
Some Remarks on Persecution Pathology
Authors: A. Braun
Journal: Psychotherapy and Psychosomatics (1974)

The author's observations on a group of 284 ex-persecuted people originating from Eastern Europe are based on 8 years of treatment and led to the following remarks: (a) a short second free interval after emigration could be observed; (b) a psychosomatosocial diagnosis can only be established by a long-term observation which shows the dynamic process of the disease; (c) the patient's resistance against psychiatric expertizing and the often observed defence of the psychiatrist against the confrontation with the persecution are discussed; (d) children grown up in psychically injured environment often show psychic deviations.
Ectopic HOXB4 overcomes the inhibitory effect of tumor necrosis factor-α on Fanconi anemia hematopoietic stem and progenitor cells
Authors: Michael D. Milsom, Bernhard Schiedlmeier, Jeff Bailey, Mi-Ok Kim, Dandan Li, Michael Jansen, Abdullah Mahmood Ali, Michelle Kirby, Christopher Baum, Leslie J. Fairbairn, David A. Williams
Journal: Blood (2009)
Medical Information Science
Authors: Thomas L. Lincoln
Journal: JAMA (1983)

IN THE 1970s, computers evolved into sophisticated information processing and communication systems. The 1980s will demonstrate the full impact of what they can do. Much has been written about the implications of this new electronic revolution,<sup>1-5</sup>and the outlines of a new information processing world are now evident. Today we may confidently project a new generation of computer systems that will accommodate the full functional diversity that health professionals require as end users of information. Equipment exists,<sup>6</sup>dramatic examples can be demonstrated,<sup>7,8</sup>and the price is almost right. Without preempting the expertise of the systems designers who will be responsible for providing new working systems, the future should look something like this: large mainframe computers will concern themselves with bulk tasks, eg, managing common archives and reorganizing large files, mainframe satellites will be involved in printing extensive batch reports, and communication nodes will link the archives with
Expression and Nuclear Location of the Transcriptional Repressor Kaiso Is Regulated by the Tumor Microenvironment
Authors: Adelheid Soubry, Jolanda van Hengel, Eef Parthoens, Cecile Colpaert, Eric Van Marck, David Waltregny, Albert B. Reynolds, Frans van Roy
Journal: Cancer Research (2005)

Kaiso is a BTB/POZ zinc finger protein originally described as an interaction partner of p120ctn. In cultured cell lines, Kaiso is found almost exclusively in the nucleus, where it generally acts as a transcriptional repressor. Here, we describe the first in situ immunolocalization studies of Kaiso expression in normal and cancerous tissues. Surprisingly, we found striking differences between its behavior in monolayers of different cell lines, three-dimensional cell culture systems, and in vivo. Although nuclear localization was sometimes observed in tissues, Kaiso was more often found in the cytoplasm, and in some cell types it was absent. In general, Kaiso and p120ctn did not colocalize in the nucleus. To examine this phenomenon more carefully, tumor cells exhibiting strong nuclear Kaiso staining in vitro were injected into nude mice and grown as xenografts. The latter showed a progressive translocation of Kaiso towards the cytoplasm over time, and even complete loss of expression, especially in the center of the tumor nodules. When xenografted tumors were returned to cell culture, Kaiso was re-expressed and was once again found in the nucleus. Translocation of Kaiso to the cytoplasm and down-regulation of its levels were also observed under particular experimental conditions in vitro, such as formation of spheroids and acini. These data strongly imply an unexpected influence of the microenvironment on Kaiso expression and localization. As transcriptional repression is a nuclear event, this phenomenon is likely a crucial factor in the regulation of Kaiso function.
Number of CD4<sup>+</sup> Cells and Location of Forkhead Box Protein P3–Positive Cells in Diagnostic Follicular Lymphoma Tissue Microarrays Correlates With Outcome
Authors: Abigail M. Lee, Andrew J. Clear, Maria Calaminici, Andrew J. Davies, Suzanne Jordan, Finlay MacDougall, Janet Matthews, Andrew J. Norton, John G. Gribben, T. Andrew Lister, Lindsey K. Goff
Journal: Journal of Clinical Oncology (2006)

To examine the immune microenvironment in diagnostic follicular lymphoma (FL) biopsies and evaluate its prognostic significance.Immunohistochemistry was used to study numbers and location of cells staining positive for immune cell markers CD4, CD7, CD8, CD25, CD68, forkhead box protein P3 (FOXP3), T-cell intracellular antigen-1, and Granzyme B in tissue microarrays of paraffin-embedded, diagnostic lymph node biopsies taken from 59 FL patients who lived less than 5 years (short-survival group; n = 34) and more than 15 years (long-survival group; n = 25).CD4 and FOXP3 expression were significantly different between the two groups. Samples from the long-survival group were more likely than those from the short-survival group to have CD4+ staining cells and to have FOXP3-positive cells in a perifollicular location.This study has identified differences in immune cell composition of the diagnostic FL lymph node immune microenvironment and these have the potential for use as prognostic biomarkers in a routine histopathology setting.
EFFECT OF THE COMPOSITION OF THE GASEOUS AND AQUEOUS ENVIRONMENTS ON THE SURVIVAL OF TUBERCLE BACILLI IN VITRO
Authors: René J. Dubos
Journal: The Journal of Experimental Medicine (1953)

Tubercle bacilli die much more rapidly under anaerobic than under aerobic conditions. Anaerobically, the rate of death is accelerated by increased CO(2) pressure, and when certain metabolites (lactate for example) are present in the medium. Death of the bacilli under certain conditions of anaerobiosis is accompanied by loss of ability to take the acid-fast stain and by progressive cellular disintegration. These findings are discussed in relation to (a) the glycolytic equipment of tubercle bacilli, (b) their fate in tuberculous lesions.
Mir-24 Regulates Junctophilin-2 Expression in Cardiomyocytes
Authors: Ming Xu, Hao-Di Wu, Rong-Chang Li, Hai-Bo Zhang, Meng Wang, Jin Tao, Xin-Heng Feng, Yun-Bo Guo, Su-Fang Li, Shao-Ting Lai, Peng Zhou, Lin-Lin Li, Hua-Qian Yang, Guan-Zheng Luo, Yan Bai, Jianzhong J. Xi, Wei Gao, Qi-De Han, You-Yi Zhang, Xiu-Jie Wang, Xu Meng, Shi-Qiang Wang
Journal: Circulation Research (2012)

Failing cardiomyocytes exhibit decreased efficiency of excitation-contraction (E-C) coupling. The downregulation of junctophilin-2 (JP2), a protein anchoring the sarcoplasmic reticulum to T-tubules, has been identified as a major mechanism underlying the defective E-C coupling. However, the regulatory mechanism of JP2 remains unknown.To determine whether microRNAs regulate JP2 expression.Bioinformatic analysis predicted 2 potential binding sites of miR-24 in the 3'-untranslated regions of JP2 mRNA. Luciferase assays confirmed that miR-24 suppressed JP2 expression by binding to either of these sites. In the aortic stenosis model, miR-24 was upregulated in failing cardiomyocytes. Adenovirus-directed overexpression of miR-24 in cardiomyocytes decreased JP2 expression and reduced Ca(2+) transient amplitude and E-C coupling gain.MiR-24-mediated suppression of JP2 expression provides a novel molecular mechanism for E-C coupling regulation in heart cells and suggests a new target against heart failure.
Cerebrospinal Fluid Penicillin Levels During Therapy for Latent Syphilis
Authors: John Ducas
Journal: JAMA (1981)

Cerebrospinal fluid and serum penicillin levels were determined in patients with latent syphilis. Mean serum concentration one week after the third weekly dose of 2.4 million units penicillin G benzathine was 0.32 units/mL. Concurrent administration of probenecid orally produced a mean serum penicillin level of 0.41 units/mL. Doubled penicillin doses without and with daily orally administered probenecid resulted in mean serum concentrations of 0.75 and 1.00 units/mL, respectively. Two of six patients in the last group had CSF penicillin concentrations greater than 0.03 units/mL.
Dibenzyline: Results of Therapy in Patients with Hypertension and a Comparison with Hexamethonium, 1-Hydrazinophthalazine and Semipurified Extracts of Veratrum
Authors: Sam I. Miller, Ralph V. Ford, John H. Moyer
Journal: New England Journal of Medicine (1953)

ALTHOUGH etiologic factors in hypertensive vascular disease are probably numerous, pharmacologic study indicates that in many cases a common denominator is overactivity of the sympathetic nervous system. Therefore, a drug that will specifically block the transmission of impulses over the sympathetic nervous system should be a valuable therapeutic agent for this disease. Dibenzyline (N-phenoxyisoprophyl-N-benzyl-β-chlorethylamine)¶ is a specific, orally active, adrenergic blocking agent that we have used in the treatment of 32 patients under hospital and outpatient conditions. A comparison of the results obtained with this drug and those obtained with hexamethonium, 1-hydrazinophthalazine (Apresoline) and the Veratrum viride alkaloids (Veriloid and . . .
Circadian Rhythm of Plasma 11-Hydroxycorticosteroids in Psychiatric Disorders
Authors: R. T. W. L. Conroy, B. D. Hughes, J. N. Mills
Journal: BMJ (1968)

Studies of the circadian rhythm in plasma 11-O.H.C.S. levels showed that a subgroup of affective psychotics had higher plasma 11-OHCS values as compared with schizophrenic and other psychotic subgroups, and a somewhat less regular rhythm. One patient with depression who was studied over 48-hour periods showed a reduction in plasma 11-OHCS levels with clinical recovery. An accentuated fall and rise in plasma 11-OHCS values in the night and early morning samples, respectively, was observed in the schizophrenic subgroup.
Pericardial fluid from patients with unstable angina induces vascular endothelial cell apoptosis
Authors: Atsushi Iwakura, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Shigetake Sasayama, Masashi Komeda
Journal: Journal of the American College of Cardiology (2000)
Polyarteritis Nodosa
Authors: GEORGE C. GRIFFITH, I. LUTFI VURAL
Journal: Circulation (1951)

The correlation of the clinical and postmortem findings shows that there is no close relationship between the syndrome of polyarteritis nodosa and the allergic states, that pain is the most common symptom, that congestive heart failure is the common cause of death. There is no consistent relationship of the symptomatology referable to the gastrointestinal, central nervous, and pulmonary systems to the pathologic lesions found. Above all, it is to be noted that although hypertension is one of the most frequent signs of polyarteritis, it may develop very late. Therefore, the rejection of this diagnosis because of the absence of hypertension will lead to error, as may the absence of eosinophilia and subcutaneous nodules.
Pediatric Emergency Medicine: A Comprehensive Study Guide
Authors: James F. Wiley
Journal: JAMA (1996)

This is the first edition of a medium-sized paperback text that is intended as a resource for practitioners of emergency care as well as the larger audience of physicians who intermittently encounter seriously ill or injured children. The book's design closely resembles that of<i>Emergency Medicine: A Comprehensive Study Guide</i>, edited by Tintinalli et al, and published by the same American College of Emergency Physicians (ACEP)/ McGraw-Hill consortium (see accompanying review).<i>Pediatric Emergency Medicine</i>expands by many times the meager 107 pages devoted to pediatrics in the Tintinalli et al volume. The relationship between the two books is not stated, but they share a unified logo, color scheme, and cover layout. <i>Pediatric Emergency Medicine</i>contains 125 chapters by authors ranging from medical students to eminent senior faculty within and outside pediatrics and emergency medicine. The chapters are organized into 21 sections, primarily organ-system-based, with a few covering broader issues, such
"NONSPLINTING TREATMENT OF FRACTURES OF ELBOW JOINT"
Authors: D. H. O'Donoghue
Journal: JAMA (1942)

<h3>To the Editor:—</h3> I have read with a great deal of concern the article appearing in the March 21 issue ofThe Journalby Dr. A. A. Neuwirth, entitled "Nonsplinting Treatment of Fractures of the Elbow Joint." It seems that in these times it will be unavoidable that a great many traumatic conditions must be treated by many physicians who have not been especially trained in this line of procedure. For this reason I think it is particularly important that the undoubted advantage incident to anatomic reposition should not be unduly minimized. Certain it is that it is not always possible to obtain anatomic reposition; but equally certain it is that, if anatomic reposition can be obtained without interference with function, this should be the goal, particularly in growing children. I question very seriously the advisability of oversimplification of the problem of treating fractures about the elbow and of the
Seroconversion from Hepatitis B e antigen to Anti-HBe in Acute Hepatitis B Virus Infection
Authors: Tatsuya Aikawa, Hiroshige Sairenji, Seiichi Furuta, Kendo Kiyosawa, Toshio Shikata, Mitsunobu Imai, Yuzo Miyakawa, Yuko Yanase, Makoto Mayumi
Journal: New England Journal of Medicine (1978)

SINCE the description of hepatitis B e antigen (HBeAg) and corresponding antibody to the antigen in 1972,1 these entities have attracted attention because of their apparent clinical implications. The presence of HBeAg in the serum of patients with acute Type B hepatitis has been said to indicate ongoing liver damage and a poor prognosis.2 , 3 However, the clinical implications of HBeAg cannot be evaluated without more information about the appearance and disappearance of the antigen in the natural course of acute hepatitis B virus infection.The study of the temporal course of HBeAg and antibody to it in the serum of . . .
Fibrocystic Disease of the Pancreas
Authors: W. J. Matheson
Journal: BMJ (1949)

A case of rheumatoid arthritis is described in which bouts of high fever occurred over a period of three months and of low-grade fever continued for a further four months before the diagnosis was evident.On two occasions a temperature of 105.20 F. (40.70 C.) was recorded after a rigor.The highest leucocyte count was 30,800, recorded on admission; the next highest was 26,200 eighteen weeks later.My thanks are due to Dr. G. D. Kersley for his help and for details of the patient's treatment and progress while