tbuckley/cabot-search huggingface dataset:
Drug Interference with Measurement of Adrenal Hormones in Urine: Analgesics and Tranquilizer-Sedatives
Authors: PHILIP E. CRYER
Journal: Annals of Internal Medicine (1971)

Twenty-four-hour urinary 17-hydroxycorticoids, free 11-hydroxycorticoids, 17-ketosteroids, and catecholamines were measured repetitively in a volunteer subject during control and base-line periods and during the short-term ingestion of relatively small doses of commonly used analgesic and tranquilizer-sedative drugs. The ingestion of propoxyphene, 65 mg, three times daily, was associated with significant depression of the urinary 17-hydroxycorticoids and 17-ketosteroids; significant depression of the 17-hydroxycorticoids and free 11-hydroxycorticoids occurred during the ingestion of pentazocine, 50 mg, twice daily. In the dosages used, the short-term ingestion of acetylsalicylic acid, acetaminophen, chlordiazepoxide, diazepam, phenobarbital, or diphenhydramine did not interfere with the measurement of 17-hydroxycorticoids, free 11-hydroxycorticoids, or 17-ketosteroids in the urine. None of the drugs tested interfered with the measurement of urinary catecholamines, norepinephrine, or epinephrine.
NSCLC and HER2: Between Lights and Shadows
Authors: Giuseppina Rosaria Rita Ricciardi, Alessandro Russo, Tindara Franchina, Giuseppa Ferraro, Mariangela Zanghì, Antonio Picone, Antonino Scimone, Vincenzo Adamo
Journal: Journal of Thoracic Oncology (2014)

The therapeutic landscape of non-small-cell lung cancer (NSCLC) has dramatically changed in the last few years with the introduction of molecularly targeted agents, leading to unprecedented results in lung tumors with a paradigmatic shift from a "one size fits all" approach to an histologic and molecular-based approach. The discovery of epidermal growth factor receptor (EGFR) mutations in NSCLC in 2004 and the marked response to the EGFR tyrosine kinase inhibitor gefitinib, in a small subset of patients harboring these genetic abnormalities, stimulated the study of other kinase mutants involvement in NSCLC. The incredible story of ALK rearranged tumors, with the rapid Food and Drug Administration approval of Crizotinib after only 4 years from the discovery of EML4-ALK translocation in NSCLC, has profoundly influenced the concept of drug development in NSCLC, paving the way to a novel series of molecularly selected studies with specific inhibitors. The identification of these oncogenic drivers has dramatically changed the genetic landscape of NSCLC moving away from the old concept of a large indistinct histological entity to a combination of rare clinically relevant molecular subsets. Recently, a renewed interest has been emerging on the human epidermal growth factor-2 (HER2) pathway. Genetic aberrations of this signaling pathway have been reported over time to be associated in NSCLC with different sensitivity to the EGFR tyrosine kinase inhibitors, to have a possible prognostic role and more recently HER2 amplification has been emerged as a possible mechanism in EGFR-mutated tumors of acquired resistance to the EGFR tyrosine kinase inhibitors. In addition, dysregulation of the HER2 pathway, in particular HER2 mutations (mostly, in-frame exon 20 insertions), may represent a possible novel therapeutic target in NSCLC, paving the way for a new generation of targeted agents in NSCLC. Since anecdotal case reports of clinical activity of anti-HER2 agents in NSCLC patients with HER2 mutations, several targeted agents have been evaluated in HER2-mutated patients, generating a growing interest upon this oncogenic driver, leading to the design of molecularly selected trials with anti-HER2 compounds and the rediscover of hastily thrown out drugs, such as neratinib. The aim of this article is to provide an overview of the role of HER2 dysregulation in NSCLCs, trying to throw a light not only on the strengths but also the weaknesses of the studies conducted so far. It is a long way to the clinical implementation of these biomarkers and probably the increasing use of next generation sequencing techniques, the creation of large multi-institutional molecular testing platforms and the design of rationally based trials can get closer personalized medicine in NSCLC.
Emotional Trauma and Thyroxine
Authors: GEORGE L. JACKSON
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 February 1986Emotional Trauma and ThyroxineGEORGE L. JACKSON, M.D.GEORGE L. JACKSON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-104-2-289_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In a practice that specializes in patients with thyroid disorders, the physician may be asked to render an opinion concerning the probability that physical or mental trauma has been a factor in the development or persistence of hyperthyroidism. I hope that the following report may assist others confronted with this question.A 32-year-old black woman was first seen 8 May 1983, after referral by her family physician, with a diagnosis of hyperthyroidism manifest by the usual symptoms and blood chemical findings. She was advised to use goitrogens. Shortly after beginning propylthiouracil therapy, she developed dermatologicsensitivity. Methimazole was... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: GEORGE L. JACKSON, M.D.Affiliations: Harrisburg Hospital Harrisburg, PA 17101 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1986Volume 104, Issue 2Page: 289-289KeywordsBloodEmotionsHyperthyroidismThyroid diseasesThyroxine ePublished: 1 December 2008 Issue Published: 1 February 1986 PDF downloadLoading ...
In vitro cellular tropism of human B-lymphotropic virus (human herpesvirus-6).
Authors: P Lusso, P D Markham, E Tschachler, F di Marzo Veronese, S Z Salahuddin, D V Ablashi, S Pahwa, K Krohn, R C Gallo
Journal: The Journal of Experimental Medicine (1988)

We investigated the cellular tropism of human B-lymphotropic virus (HBLV) (also designated Human Herpesvirus-6) in vitro by infecting fresh MN cells from normal human adult peripheral blood, umbilical cord blood, bone marrow, tonsil, and thymus. Cultures from all the sources examined contained infectable cells, as shown by the appearance of characteristic enlarged, round-shaped, short-lived cells expressing HBLV-specific markers. Detailed immunological analysis demonstrated that the vast majority of these cells expressed T cell-associated antigens (i.e., CD7, CD5, CD2, CD4, and to a lesser extent, CD8). The CD3 antigen and the TCR-alpha/beta heterodimer were not detectable on the surface membrane, but were identified within the cytoplasm of HBLV-infected cells, by both immunofluorescence and radioimmunoprecipitation assay. A proportion of the HBLV-infected cell population also expressed the CD15 and class II MHC DR antigens. By means of immunoselection procedures it was possible to show that a consistent proportion of HBLV-infectable cells were contained within the CD3-depleted immature T cell population, while the depletion of CD2+ cells completely abrogated the infectability of the cultures. Northern blot analysis confirmed the T cell origin of HBLV-infected cells, demonstrating the expression of full size TCR-alpha and -beta chain mRNA. In addition to fresh T cells, HBLV was able to infect normal T lymphocytes expanded in vitro with IL-2 for greater than 30 d. These results indicate that HBLV is selectively T cell tropic in the course of the in vitro infection of normal mononuclear cells and may therefore be directly involved in the pathogenesis of T cell related hematological disorders. In particular, in light of the cytopathic effect exerted in vitro on CD4+ T lymphocytes, a possible role of HBLV in immune deficiency conditions should be considered.
Cost effective drug budgets.
Authors: M. G. Carter, G. Holman
Journal: BMJ (1989)

Look after the speaker's gastronomic needs.The speaker, having spoken, is often delayed by people coming up to him or her or having to collect the slides.He may then have to stand at the end of the queue for coffee and has too little time to drink it, or arrives late for lunch when much of the food has gone.Take the speaker to the front of the queue or have these refreshments put aside.
Collateral Pathways Observed by Radionuclide Superior Cavography in 70 Patients with Superior Vena Caval Obstruction
Authors: TOSHIHIRO MURAMATSU, TATSUYA MIYAMAE, YUTAKA DOHI
Journal: Clinical Nuclear Medicine (1991)

Schematic representations of collateral pathways that have developed in association with superior vena caval obstruction have been established in studies using radionuclide superior cavography (RNSC). However, these were hampered by the poor resolution of earlier scintillation cameras. Using a modern scintillation camera, we performed RNSC in 70 patients with obstruction of the superior vena caval system, and examined the differences in collateral pathways in the presence or absence of obstruction of the azygos vein. RNSC visualized the site of obstruction and collateral pathways far more readily than in prior studies. When the orifice of the azygos vein was not obstructed, collateral flow drained into the azygos system. When it was obstructed, however, the collaterals drained into the inferior vena caval system. An important collateral pathway comprising the contralateral brachiocephalic vein and the jugular venous arch was also found, which has not previously been reported. Our diagrams of collateral circulation may provide a means of determining the site of obstruction in the superior vena caval system by RNSC.
Stem‐Cell Niche Based Comparative Analysis of Chemical and Nano‐mechanical Material Properties Impacting Ex Vivo Expansion and Differentiation of Hematopoietic and Mesenchymal Stem Cells
Authors: Jinlin Jiang, Eleftherios T. Papoutsakis
Journal: Advanced Healthcare Materials (2012)

Abstract The ability of stem cells to self‐renew with minimal or no differentiation and, when appropriately cued, to give rise to many types of progenitor and mature cells, is the basis for applications in regenerative and transfusion medicine, but also in drug discovery and in vitro toxicology. Inspired by the complex interactions between stem cells and their microenvironment, the so‐called stem‐cell niche, the properties of supporting biomaterials, including surface biochemistry, topography (type, size, organization, and geometry of nanostructures), and mechanical properties, have been identified as important determinants of stem‐cell fate in vitro. 3D culture environments that could recapitulate the complexity of the in vivo stem‐cell microenvironment could further expand the complexity and repertoire of engineered environments with exciting translational applications. Herein, the material aspects that affect the expansion and differentiation fate of adult hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stem cells (MSCs), two powerful cell types that co‐reside in the bone‐marrow niche, but with distinct, sometime complementary, differentiation fates, properties, and translational applications, are examined. Although MSCs are adherent cells and, in contrast, HSPCs are non‐ or weakly adherent cells, both can sense and respond to material properties, including surface (bio)chemistry, ECM composition, topography, and matrix elasticity, possibly through similar molecular mechanisms.
REPORTS OF UTERINE MALFORMATIONS
Authors: E. M. PRINCE
Journal: JAMA (1913)

Many text-books on gynecology assert that a double uterus, or the absence of the uterus, is a rare occurrence. This has not been my experience. Although my surgical work is confined entirely to private patients, I have seen half a dozen of these anomalies in the course of a few years, so that I can but wonder why in the large clinics embracing the enormous amount of charity and private surgical work, they should be classed as extremely rare.  These malformations are caused by developmental defects in the early embryonic stage. The vagina and uterus are both developed by the coalescence of the lower two-thirds of the mullerian ducts, and the absorption of their inner wall. If these ducts fail to unite, or the septum is not absorbed, a deformity results to a more or less extent. If the ducts unite and the septum persists there will be a double
Reduction of inflammatory cytokine expression and oxidative damage by erythropoietin in chronic heart failure
Authors: Y LI, G TAKEMURA, H OKADA, S MIYATA, R MARUYAMA, L LI, M HIGUCHI, S MINATOGUCHI, T FUJIWARA, H FUJIWARA
Journal: Cardiovascular Research (2006)

Late treatment with erythropoietin (EPO), as well as the administration before the onset of or during the acute stage of myocardial infarction (MI), has recently been shown to mitigate post-MI heart failure. We investigated the mechanisms, including the downstream signaling pathways, for the beneficial effect of late treatment with EPO on chronic post-MI heart failure.EPO (1500 U/kg, twice a week) was administered to mice beginning 6 weeks after induction of large MI. The EPO treatment for 4 weeks diminished left ventricular dilatation and improved function. It significantly reduced inflammatory cell infiltration and fibrosis, and increased vascular density in noninfarcted areas. The elevated levels of the inflammatory cytokines interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and transforming growth factor-beta1 seen in the failing hearts were returned nearly to control levels by EPO treatment. Oxidative damage in surviving cardiomyocytes was also significantly attenuated by EPO. Expression of EPO receptor was upregulated in failing hearts, and EPO treatment led to myocardial activation of signal transducer and activator of transcription-3 (Stat3), Stat5, and Akt. These in vivo effects of EPO were confirmed in vitro in experiments that showed the anti-inflammatory and anti-oxidant effects of EPO to be mediated via Stat and Akt activation. Finally, the beneficial effects of EPO were found to persist for 4 weeks after discontinuing treatment.It thus appears that Stat-mediated reduction of inflammation and cytokine production and Akt-mediated attenuation of oxidative stress accompany the beneficial effects of late treatment with EPO on chronic post-MI heart failure.
Abstract 5753: RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth
Authors: Georgia Hatzivassiliou, Kyung Song, Ivana Yen, Barbara J. Brandhuber, Daniel J. Anderson, Ryan Alvarado, Mary JC Ludlam, David Stokoe, Susan L. Gloor, Guy Vigers, Tony Morales, Ignacio Aliagas, Bonnie Liu, Steve Sideris, Klaus Hoeflich, Bijay S. Jaiswal, Somasekar Seshagiri, Hartmut Koeppen, Marcia Belvin, Lori S. Friedman, Shiva Malek
Journal: Cancer Research (2010)

Abstract Activating mutations in KRAS or B-RAF are found in over 30% of all human tumors and targeting this pathway could have broad therapeutic impact. Small molecule ATP-competitive RAF kinase inhibitors have potent anti-tumor effects on B-RAFV600E tumors but, in contrast to MEK inhibitors, are not potent against RAS mutant tumor models, despite RAF functioning as a key effector downstream of RAS and upstream of MEK. In this study we show that ATP-competitive RAF inhibitors have two opposing mechanisms of action depending on cellular context. In B-RAFV600E tumors, RAF inhibitors effectively block the MAPK signaling pathway and decrease tumor growth. Surprisingly, in KRAS mutant and RAS/RAF wildtype tumors, RAF inhibitors activate the RAF/MEK/ERK pathway in a RAS-dependent manner, thus enhancing tumor growth in some xenograft models. Inhibitor binding activates wildtype RAF isoforms by inducing dimerization, membrane localization and interaction with RAS-GTP. These events occur independently of kinase inhibition and are, rather, linked to direct conformational effects of inhibitors on the RAF kinase domain. Based on these findings, we demonstrate that ATP-competitive kinase inhibitors can have opposing functions as inhibitors or activators of signaling pathways, depending upon cellular context. In addition, this work provides new insights into the therapeutic use of ATP-competitive RAF inhibitors. 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 5753.
Surgical Treatment of Tricuspid Stenosis
Authors: THOMAS J. E. O'NEILL, O. HENRY JANTON, ROBERT P. GLOVER
Journal: Circulation (1954)

In patients suffering with chronic valvular disease who are diagnosed as having mitral stenosis, there are found a few who have an associated tricuspid stenosis. The diagnosis of this combination of lesions is difficult. The unique opportunity to study the hemodynamics of "pure" tricuspid stenosis was presented when a patient, originally diagnosed as mitral stenosis, had in fact both lesions, and was treated by mitral commissurotomy. Subsequently tricuspid stenosis was suspected clinically and was demonstrated by serial catheterization studies. Tricuspid commissurotomy was performed four years after mitral commissurotomy.
Re: Increased Virus Shedding With Aspirin Treatment of Rhinovirus Infection
Authors: R. S. Griffith
Journal: JAMA (1976)

To the Editor.—  The article by Stanley et al that describes increased virus shedding with aspirin treatment did not include mention of a possible mechanism of action. Several years ago, we conducted a simple study that may explain the increased virus shedding. Noting that our virologist used an incubator setting of 35 C for optimal growth of respiratory tract virus and that a setting of 37 C was a deterrent to viral growth ( Micro  biology , ed 2. New York, Harper & Row Publishers, 1973, p 1212), we placed tissue cultures inoculated with influenza virus in incubators with temperatures of 35, 37, and 39 C. Little cytopathogenicity was observed at the fever temperature of 39 C. Some cytopathogenicity of the influenza virus was observable at the body temperature of 37 C, but optimal growth of the virus (as shown by extensive cytopathogenicity with morphologic changes, loss of attachment, and death) was
S71 Are Quality Standards And Accredited Centres For Mediastinal Staging With Ebus Needed? A Report From The Manchester Cancer Ebus Group
Authors: M. Evison, P. Crosbie, J. Morris, J. Martin, R. Shah, H. Doran, J. Hoyle, S. Bailey, D. Rana, R. Sundar, R. Booton
Journal: Thorax (2014)

<h3>Introduction</h3> Mediastinal staging in lung cancer is a core function of EBUS-TBNA. There has been an explosion of EBUS -TBNA services across the UK over recent years. However, quality standards and adherence to such standards are not widely known. The aim of this study was to describe the current practices of four independent EBUS centres serving a large UK cancer network. <h3>Materials and Methods</h3> In 2012, the number of centres providing EBUS-TBNA in this Network increased from one to four. This prompted the development of an EBUS sub-group and service specification that mandates the collection of pre-defined data for all EBUS procedures. Analysis of this prospectively maintained database was undertaken for this report. <h3>Results</h3> 741 lung cancer patients underwent EBUS-TBNA in the study period. 56.4% (418/741) were for nodal staging, with the remaining performed for pathological confirmation of lung cancer. The proportion of staging procedures performed at each centre varied significantly (range 4.8% - 80.3%, p &lt; 0.0001). In those patients undergoing EBUS for mediastinal staging, the average number of lymph stations sampled per procedure varied from 1.3 to 1.9 across the four centres and the proportion of patients with 3 or more stations sampled varied from 0% to 26.6%. Furthermore, there was variability in the rate of inadequate sampling (2.4–7.6%), sensitivity (69.2–90.5%), negative predictive value (50–87.5%) and rate of surgical sampling of negative nodes (6.3–35.0%) across the EBUS centres. <h3>Discussion</h3> There is variability in practice in all parameters of EBUS practice examined in our Network, in the absence of agreed standards and protocols for mediastinal staging. Such protocols and standards have now been agreed and implemented across our Network and the EBUS sub-group is committed to ongoing data collection and publication to drive quality outcomes in this pivotal lung cancer service.
CREATININ AND CREATIN METABOLISM IN CHILDREN
Authors: J. P. SEDGWICK
Journal: JAMA (1910)

In a lecture, delivered before the Harvey Society two years ago, Folin<sup>1</sup>said: I venture to predict that we shall learn more concerning the abnormal or subnormal metabolism of the sick on the basis of creatinin and creatin determinations alone than could be learned in another thirty years by means of the nitrogen determinations of the past. Creatin is methyl guanidin acetic acid and may be converted into creatinin by the withdrawal of one molecule of water. It would seem remarkable that creatin, which is the most important of the extractives of muscle and the chief constituent of broths and beef extracts, and creatinin, a constant constituent of the urine, should have received so little attention in clinical medicine. This seems to be even more striking when we consider that uric acid, which appears usually in smaller quantity, both absolutely and in nitrogen content, in human urine, has been
Abstract 5376: Expression of histone deacetylases (HDACs) 1, 2, 3 and 7 in pancreatic cancer cell lines: The role of indole-3-carbinol.
Authors: Beverly D. Lyn-Cook, Li Pang, Lascelles E. Lyn-Cook, Beverly Word, George Hammons
Journal: Cancer Research (2013)

Abstract Pancreatic cancer has the poorest prognosis of most cancers, mainly due to its resistant phenotype. Early or late biomarkers are greatly needed in this cancer. Scientists have shown that epigenetic mechanisms may be involved in the etiology and progression of pancreatic cancer. Epigenetic changes involve modification of the DNA through hyper- and hypo-methylation, histone modification and modulation in expression of microRNAs. Histone deacetylases modify tails on the histones, which can result in repressive chromatin formation and inactivation of specific genes. This study, using real-time PCR, examined the level of HDACs 1, 2, 3 and 7 in four pancreatic cancer cell lines (BXPC, CFPAC,ASPC and MIA). The highest level of expression of HDAC 1 and 3 was found in CFPAC and MIA cells compared to BXPC and ASPC cells. Indole-3 carbinol, in previously published studies from our laboratory, have shown several anti-cancer activities, including the re-expression of p16 in MIA cells (Lyn-Cook et al, 2010 Anticancer Res., 30:4907-4914). The current study demonstrated that indole-3-carbinol at concentrations of 20 μM and 100 μM significantly decreased expression of HDAC 3 by 2-fold and 3-fold in MIA cells, respectively. Results further showed that indole-3 carbinol decreased expression of HDAC 1 in CFPAC cells and HDAC 7 in BXPC cells by 2-fold. No change in expression was shown in any of the cell lines on HDAC 2. This study showed that indole-3-carbinol may exert histone deacetylase inhibitory effects. Further studies are needed to confirm these results. Specific HDACs as potential targets for pancreatic cancer are growing among the scientific community. HDACs are known to be regulators of growth, differentiation and cell death and dysfunction of transcriptional repression mediated by HDACs may lead to the development of cancer. Citation Format: Beverly D. Lyn-Cook, Li Pang, Lascelles E. Lyn-Cook, Beverly Word, George Hammons. Expression of histone deacetylases (HDACs) 1, 2, 3 and 7 in pancreatic cancer cell lines: The role of indole-3-carbinol. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5376. doi:10.1158/1538-7445.AM2013-5376