DOCSLIB.ORG

THE AMERICAN JOURNAL of CANCER a Continuation of the Journal of Cancer Research

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
THE AMERICAN JOURNAL of CANCER a Continuation of the Journal of Cancer Research THE AMERICAN JOURNAL OF CANCER A Continuation of The Journal of Cancer Research - - VOLUMEXXX AUGUST,1937 NUMBER4 THE TRANSMISSIBLE AGENT OF THE ROUS CHICKEN SARCOhIA NO. 1 JAMES W. JOBLING, M.D., E. E. SPROUL, M.D., AND SUE STEVENS, M.A. (From the Department of Patlzology, College of Physicians and Surgeons, Columbia University) That animal tumors can be successfully transmitted within the species has been known for many years. The process was easily understood so long as living cells were required for transmission, the growth presumably resulting from continued division of the viable tumor cells. The discovery by Rous in 19 11 ( 1) that a chicken sarcoma could be produced in normal fowl by in- jection of a cell-free extract of the tumor considerably altered the general point of view, but at the same time offered the hope that the nature of the responsible agent would eventually be established. The hypotheses which have stimulated widely varying experimentation may be roughly divided into those regarding the agent as of extrinsic origin and those seeking its source in the metabolic processes of the host itself. Interpretation of the development of the Rous sarcoma as the result of infection with a living parasite, a virus more related to the causative agent of chicken pox, vaccinia, herpes, etc., is supported chiefly by analogy. An- drewes (2) has been most impressed by the properties borne in common by the Rous sarcoma and the more readily accepted virus infections. Nor does he accept the variation in type of response as a serious discrepancy, since he shows that the viruses can stimulate hyperplasia as well as necrosis and that all gradations between the two can be found. This view is also held by Rous (3), who considers that his more recent work with the Shope papilloma has provided him with confirmatory evidence. A somewhat more tangible means of investigation has been supplied by the method of ultra-centrifugation. Ledingham and Gye (4) report the concentration, by this procedure, of "elementary bodies" from the Rous sarcoma filtrate which they believe represent the causative factor of the disease. 1 This investigation has been aided by a grant from the Josiah Macy, Jr. Foundation. 667 668 JAMES W. JOBLING,E. E. SPROUL AND SUE STEVENS Among the extrinsic causes of cancer we must also classify the irritants and perhaps, more specifically, traumatic effects. Wells (5) stated in 1931 that " the trend of these results of recent cancer research is in support of the old view that cancer is usually the result of protracted stimulation of tissue growth by non-specific agents acting on tissues, the susceptibility of which is deter- mined by their hereditary background." Knox (6) and Ewing (7) find no adequate support of a relationship between trauma and tumor growth, but the theory of a causative relation is still considered plausible by many (8). Re- cent stimulus has been offered by Wolbach's histological studies on the tissues acted upon by several synthetic carcinogenic substance^.^ He finds necrosis followed by normal repair which imperceptibly becomes transformed into a new growth. The group believing that the causative agent of cancer, or more specifically of the chicken sarcoma, is endogenous is further divided by diverse views as to its nature. It has been called an enzyme, without further elucidation of its actual nature (9). It has been likened to the hormones (10, 11) in be- havior and chemical composition, and there are those who believe more con- cretely that it may be derived from the sex hormones by some alteration in sterol metabolism (12). Murphy (13) favors the term " transmissible mutagen" for the substance appearing in the cell-free tumor filtrates, indi- cating that the agent is capable of directing the specific development of the cell into abnormal channels and that it is further elaborated by this altered cell. Ludford (14) has also expressed somewhat similar ideas, although not stressing the transmissibility of the mutagen. A decade ago it seemed that Gye (15) might reconcile these opposing forces by his suggestion that an exogenous universal cancer agent, which he termed a virus, received its specificity when combined with an intrinsic factor, presumably elaborated by the various cell types. His experiments, however, were not corroborated by others nor by later developments in his own laboratory. Such unrelated views have provided the means of unearthing a formidable number of facts regarding the character of tumor growth without arriving at a tenable explanation of the course of events. This investigation was begun following the observation that independent studies on distinct phases of the problem indicated the importance of the lipids in abnormal and physiological growth processes. The most outstanding was undoubtedly the synthesis by Cook, Barry and their associates (16, 17) of a series of carcinogenic hydro- carbons in the form of condensed ring compounds, recalling the structure of cholesterol. It would seem unlikely, in view of the prolonged period of ap- plication required for tumor formation, that the known chemicals act directly on the cells, but the remarkable consistency in carcinogenic activity observed in various laboratories leaves no doubt of the specificity of their action (18, 19). The significant changes which each compound suffers in the process of cell metabolism remain for future elucidation. The second most arresting observation was the alliance of the sex hor- mones with cancer and the timely discovery of the molecular structure of 2Reported at the Annual Meeting of the American Society of Pathology and Bacteriology, Chicago, March 1937. several of these complicated substances (19, 20, 21). The recognition by the biologists of the r6le enacted by the ovarian hormone in normal develop- ment and malignant growth of the mammary gland as well as in stiniulation of hyperplastic endometrial change in mice long preceded the isolation by the chemists of these hormones. Lathrop and Loeb (22) in 1916 demonstrated the reduction in the incidence of spontaneous tumors following castration or prevention of breeding and many have subsequently corroborated and ampli- fied this statement. A new type of investigation was offered by the discovery that the follicular and luteal hormones are also phenanthrene derivatives not unlike those stimulating the growth of tumors and structurally related to the sterols (23). It remained then to demonstrate the actual production of tu- mors by injection of pure estrogenic compounds and this was accomplished by Lacassagne (24) working with a strain of mice known to develop spon- taneous mammary cancer. This achievement has been confirmed and the observation made by Loeb (20) that the estrogenic hormones can induce cancer only in those organs normally stimulated by them. Cook and Dodds (25) contributed to the subject by synthesis of a variety of compounds all possessing the tricyclic phenanthrene ring nucleus and biologically estrogenic as well as carcinogenic. The third group of studies, which led to the undertaking of our own experi- ments, had to do with the suggestion that lipids could be classified as growth- stimulating substances. Contradictory evidence has been presented by many authors whose methods of demonstrating the effect of increased lipid intake have differed widely. Robertson and Burnett (26) caused an acceleration of the growth of the Flexner-Jobling rat carcinoma by direct injection of choles- terol into the tumor; lecithin had the opposite effect. Subsequent publications by these authors as well as by Bernstein and Elias (27) and Moravek (28) have been in agreement in regard to the effect on this and other tumors of feeding and injecting these substances. One can also find the view that cholesterol, fed or injected, has no effect upon tumor development (29), and Harnes (30) claimed to have demon- strated a retarding effect when the inoculation of the Brown-Pearce rabbit carcinoma into the testis was preceded by subcutaneous administration of alcoholic brain extract in corn oil. Vassiliadis (31) embraces both assump- tions by the statement that stimulating and inhibiting substances can be found equally in the ether and acetone extracts of normal tissues tested against tar- induced tumors. The most recent observations on this subject are those of MacFadyen and Sturm (32), who demonstrated augmentation of growth of the Bashford mouse carcinoma No. 63 when the graft had been exposed to the ether-soluble fraction of mammary gland. The ether-insoluble material definitely interfered with tumor growth. It is hardly remarkable that there should exist such discrepancies when we consider that inhibiting and stimulating substances ordinarily form a close alliance, and variation in technic may easily favor the one or the other. At least the majority report some influence exerted by fats and related substances on tumor proliferation. The need for investigation of the activity of the lipid fraction of tumor tissue was further emphasized by numerous reports of the high lipid content 670 JAMES W. JOBLING,E. E. SPROUL AND SUE STEVENS of tumors as well as of the blood of tumor-bearing animals and patients. Bul- lock and Cramer (33) concluded from analytical studies on mouse and rat tumors that the phospholipids were associated with rapidity of growth. Sup- port for such a view can be found in the analysis conducted by Bierich and Lang (34), Yasuda and Bloor (35), and more recently by Haven (36). One also finds cholesterol stressed as an important factor in tumor metab- olism, reasoning from content alone. Roffo (37) has written extensively on the correlation of high cholesterol level with the growth of tumors, a view subscribed to by Correa (38) on the basis of analyses of tumors and the blood and non-tumor bearing organs of tumor animals, as well as the personal ob- servation that cholesterol, administered orally or by subcutaneous route, stim- ulated the growth of tumors.
Load more

Recommended publications
  • No Haven for the Oppressed
    No Haven for the Oppressed NO HAVEN for the Oppressed United States Policy Toward Jewish Refugees, 1938-1945 by Saul S. Friedman YOUNGSTOWN STATE UNIVERSITY Wayne State University Press Detroit 1973 Copyright © 1973 by Wayne State University Press, Detroit, Michigan 48202. All material in this work, except as identified below, is licensed under a Creative Commons Attribution-NonCommercial 3.0 United States License. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc/3.0/us/. Excerpts from Arthur Miller’s Incident at Vichy formerly copyrighted © 1964 to Penguin Publishing Group now copyrighted to Penguin Random House. All material not licensed under a Creative Commons license is all rights reserved. Permission must be obtained from the copyright owner to use this material. Published simultaneously in Canada by the Copp Clark Publishing Company 517 Wellington Street, West Toronto 2B, Canada. Library of Congress Cataloging in Publication Data Friedman, Saul S 1937– No haven for the oppressed. Originally presented as the author’s thesis, Ohio State University. Includes bibliographical references. 1. Refugees, Jewish. 2. Holocaust, Jewish (1939–1945) 3. United States— Emigration and immigration. 4. Jews in the United States—Political and social conditions. I. Title. D810.J4F75 1973 940.53’159 72-2271 ISBN 978-0-8143-4373-9 (paperback); 978-0-8143-4374-6 (ebook) Publication of this book was assisted by the American Council of Learned Societies under a grant from the Andrew W. Mellon Foundation. The publication of this volume in a freely accessible digital format has been made possible by a major grant from the National Endowment for the Humanities and the Mellon Foundation through their Humanities Open Book Program.
    [Show full text]
  • Gain-Of-Function Effects of Mutant P53 Explored Using a Three
    Gain-of-Function Effects of Mutant p53 Explored Using a Three- Dimensional Culture Model of Breast Cancer William A. Freed-Pastor Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy under the Executive Committee of the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2012 © 2011 William A. Freed-Pastor All Rights Reserved ABSTRACT Gain-of-Function Effects of Mutant p53 Explored Using a Three-Dimensional Culture Model of Breast Cancer William A. Freed-Pastor p53 is the most frequent target for mutation in human tumors and mutation at this locus is a common and early event in breast carcinogenesis. Breast tumors with mutated p53 often contain abundant levels of this mutant protein, which has been postulated to actively contribute to tumorigenesis by acquiring pro-oncogenic (“gain- of-function”) properties. To elucidate how mutant p53 might contribute to mammary carcinogenesis, we employed a three-dimensional (3D) culture model of breast cancer. When placed in a laminin-rich extracellular matrix, non-malignant mammary epithelial cells form structures highly reminiscent for many aspects of acinar structures found in vivo. On the other hand, breast cancer cells, when placed in the same environment, form highly disorganized and sometimes invasive structures. Modulation of critical oncogenic signaling pathways has been shown to phenotypically revert breast cancer cells to a more acinar-like morphology. We examined the role of mutant p53 in this context by generating stable, regulatable p53 shRNA derivatives of mammary carcinoma cell lines to deplete endogenous mutant p53. We demonstrated that, depending on the cellular context, mutant p53 depletion is sufficient to significantly reduce invasion or in some cases actually induce a phenotypic reversion to more acinar-like structures in breast cancer cells grown in 3D culture.
    [Show full text]
  • David Rittenberg 1906–1970
    NATIONAL ACADEMY OF SCIENCES DAVID RITTENBERG 1906–1970 A Biographical Memoir by DAVID SHEMIN AND RONALD BENTLEY Any opinions expressed in this memoir are those of the authors and do not necessarily reflect the views of the National Academy of Sciences. Biographical Memoirs, VOLUME 80 PUBLISHED 2001 BY THE NATIONAL ACADEMY PRESS WASHINGTON, D.C. Courtesy of Dr. Ronald Bentley DAVID RITTENBERG November 11, 1906–January 24, 1970 BY DAVID SHEMIN AND RONALD BENTLEY AVID RITTENBERG WAS a leader in the development of the D isotopic tracer technique for the study of biochemical reactions in intermediary metabolism. In a brief but his- toric paper published in Science in 1935, Rittenberg and Rudolph Schoenheimer described work at the Department of Biochemistry at Columbia University’s College of Physicians and Surgeons. Their pioneering experiments used deuterium, 2H, the heavy, stable isotope of hydrogen, to trace the fate of various compounds in the animal body. The metabolites containing 2H had properties essentially indistinguishable from their natural analogs by the methods commonly used. Nevertheless, the presence of the isotope made it possible to trace their metabolic fate. Thus, if a 2H-containing com- pound, B, was isolated after feeding the 2H-labeled com- pound, A, to an animal, the metabolic conversion A → B was established. Prophetically, these authors noted that “the number of possible applications of this method appears to be almost unlimited.” Subsequent developments have shown that they were true prophets. In the mid-1930s little was known about the chemical reactions used by living systems to synthesize and degrade cellular components. One difficulty was that methods for the isolation and purification of carbohydrates, lipids, and 3 4 BIOGRAPHICAL MEMOIRS proteins were primitive and methods for the detailed study of enzymes were lacking.
    [Show full text]
  • CHEMICAL HERITAGE FOUNDATION JEROME A. BERSON Transcript Of
    CHEMICAL HERITAGE FOUNDATION JEROME A. BERSON Transcript of an Interview Conducted by Leon Gortler at New Haven, Connecticut on 21 March 2001 (With Subsequent Corrections and Additions) Upon Jerome Berson’s death in 2017, this oral history was designated Free Access. Please note: Users citing this interview for purposes of publication are obliged under the terms of the Chemical Heritage Foundation (CHF) Center for Oral History to credit CHF using the format below: Jerome A. Berson, interview by Leon Gortler at New Haven, Connecticut, 21 March 2001 (Philadelphia: Chemical Heritage Foundation, Oral History Transcript # 0196). Chemical Heritage Foundation Center for Oral History 315 Chestnut Street Philadelphia, Pennsylvania 19106 The Chemical Heritage Foundation (CHF) serves the community of the chemical and molecular sciences, and the wider public, by treasuring the past, educating the present, and inspiring the future. CHF maintains a world-class collection of materials that document the history and heritage of the chemical and molecular sciences, technologies, and industries; encourages research in CHF collections; and carries out a program of outreach and interpretation in order to advance an understanding of the role of the chemical and molecular sciences, technologies, and industries in shaping society. JEROME A. BERSON 1924 Born in Sanford, Florida, on 10 May Education 1944 B.S., chemistry, City College of New York 1947 A.M., chemistry, Columbia University 1949 Ph.D., chemistry, Columbia University Professional Experience 1944 Hoffmann-La Roche 1944-1946 U.S. Army University of Southern California 1950-1953 Assistant Professor 1953-1958 Associate Professor 1958-1963 Professor 1963-1969 University of Wisconsin, Professor Yale University 1969-1979 Professor 1979-1992 Irénée du Pont Professor 1992-1994 Sterling Professor 1994-present Sterling Professor Emeritus of Chemistry and Senior Research Scientist Honors 1949 National Research Council Postdoctoral Fellowship, Harvard University (R.B.
    [Show full text]
  • Nobel Prizes
    W W de Herder Heroes in endocrinology: 1–11 3:R94 Review Nobel Prizes Open Access Heroes in endocrinology: Nobel Prizes Correspondence Wouter W de Herder should be addressed to W W de Herder Section of Endocrinology, Department of Internal Medicine, Erasmus MC, ’s Gravendijkwal 230, 3015 CE Rotterdam, Email The Netherlands [email protected] Abstract The Nobel Prize in Physiology or Medicine was first awarded in 1901. Since then, the Nobel Key Words Prizes in Physiology or Medicine, Chemistry and Physics have been awarded to at least 33 " diabetes distinguished researchers who were directly or indirectly involved in research into the field " pituitary of endocrinology. This paper reflects on the life histories, careers and achievements of 11 of " thyroid them: Frederick G Banting, Roger Guillemin, Philip S Hench, Bernardo A Houssay, Edward " adrenal C Kendall, E Theodor Kocher, John J R Macleod, Tadeus Reichstein, Andrew V Schally, Earl " neuroendocrinology W Sutherland, Jr and Rosalyn Yalow. All were eminent scientists, distinguished lecturers and winners of many prizes and awards. Endocrine Connections (2014) 3, R94–R104 Introduction Endocrine Connections Among all the prizes awarded for life achievements in In 1901, the first prize was awarded to the German medical research, the Nobel Prize in Physiology or physiologist Emil A von Behring (3, 4). This award heralded Medicine is considered the most prestigious. the first recognition of extraordinary advances in medicine The Swedish chemist and engineer, Alfred Bernhard that has become the legacy of Nobel’s prescient idea to Nobel (1833–1896), is well known as the inventor of recognise global excellence.
    [Show full text]
  • Title of Dissertation Goes Here in All Caps
    INSIG-MEDIATED REGULATION OF HEPATIC LIPID SYNTHESIS APPROVED BY SUPERVISORY COMMITTEE Michael S. Brown, M.D. Joseph L. Goldstein, M.D. Andrew R. Zinn, M.D., Ph.D. Keith L. Parker, M.D., Ph.D. Steven A. Kliewer, Ph.D. DEDICATION To my dearest wife Stephanie and our family INSIG-MEDIATED REGULATION OF HEPATIC LIPID SYNTHESIS by LUKE JAMES ENGELKING DISSERTATION Presented to the Faculty of the Graduate School of Biomedical Sciences The University of Texas Southwestern Medical Center at Dallas In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY The University of Texas Southwestern Medical Center at Dallas Dallas, Texas July, 2005 ACKNOWLEDGMENTS This work would not have been possible without the help of many people. First, I thank my lovely wife Stephanie for her emotional, intellectual, financial, and patient support throughout the entirety of my medical and scientific training. It has been an esteemed privilege of mine to have worked under Michael Brown and Joseph Goldstein. I can add little to the commendations and compliments that have already been bestowed on them, other than to whole-heartedly agree that they are well-deserved. I hope that some fraction of their scientific prowess, incredible energy, attention to detail, and appreciation for the big picture has rubbed off onto me and will see me through my future endeavors. I would also like to thank the members of my dissertation committee – Andrew Zinn, Keith Parker, and Steven Kliewer. Their positive attitudes and insightful comments were a tremendous support during the past two years. Much of this work is part of a larger collaboration between myself and Guosheng Liang.
    [Show full text]
  • Characterizing the Assembly and Molecular Interactions of the Fission Yeast Atg1 Autophagy Regulatory Complex
    Characterizing the assembly and molecular interactions of the fission yeast Atg1 autophagy regulatory complex by Tamiza Nanji B.Sc., M.Sc. (McMaster University) 2012, 2014 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in The Faculty of Graduate and Postdoctoral Studies (Biochemistry and Molecular Biology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2019 ©Tamiza Nanji, 2019 The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Characterizing the assembly and molecular interactions of the fission yeast Atg1 autophagy regulatory complex submitted by Tamiza Nanji in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Biochemistry and Molecular Biology Examining Committee: Calvin Yip, Biochemistry and Molecular Biology Supervisor Filip Van Petegem, Biochemistry and Molecular Biology Supervisory Committee Member Michel Roberge, Biochemistry and Molecular Biology Supervisory Committee Member Elizabeth Conibear, Medical Genetics University Examiner Chris Loewen, Cell and Developmental Biology University Examiner ii Abstract Macroautophagy, often referred to as autophagy, is a non-selective degradation mechanism used by eukaryotic cells to recycle cytoplasmic material and maintain homeostasis. Upregulated under starvation to generate molecular building blocks for ongoing cellular processes, this pathway requires the coordinated action of six multi-protein complexes, the Atg1/ULK1 complex being the first. Although, the Atg1 complex has been extensively studied in Saccharomyces cerevisiae, far less is known about the biochemical and structural properties of its mammalian counterpart, the ULK1 complex. Unlike the S. cerevisiae Atg1 complex which contains five subunits (Atg1, Atg13, Atg17, Atg29, and Atg31), the ULK1 complex consists of four proteins (ULK1, FIP200/RB1CC1, ATG13, and ATG101) that are technically more challenging to study.
    [Show full text]
  • Bile Acid Chemistry, Biology, and Therapeutics
    1 Bile Acid Chemistry, Biology, and Therapeutics During the Last 80 Years: Historical Aspects Alan F. Hofmann and Lee R. Hagey Running footline: History of bile acid research Department of Medicine, University of California, San Diego 92093-063 Downloaded from Correspondence to Alan F. Hofmann ([email protected]) or Lee R. Hagey ([email protected]) www.jlr.org Alan F. Hofmann, M.D., Telephone and fax: (858) 459-1754 Lee R. Hagey, Ph.D. Telephone (619) 543-2281 by guest, on October 30, 2017 Abbreviations: ASBT, apical sodium co-dependent bile acid transporter; AUC, area under the curve; BSEP, bile salt export pump; CDCA, chenodeoxycholic acid; CMC, critical micellization concentration; CMT, critical micellization temperature; CMpH, critical micellization pH; DCA, deoxycholic acid; FATP, fatty acid transport protein; FGF, fibroblast growth factor; FGFR4, fibroblast growth factor receptor 4; FRET, Forster resonance energy transfer; FXR, farnesoid X-Receptor; GLP-1, glucagon-like peptide 1; MDR, multidrug resistance (protein); MRP4, multidrug resistance protein 4; MTBE, methyl tertbutyl ether; NTCP, Na+ taurocholate co-transporting polypeptide; OATP, organic anion transporting polypeptide; OST, organic solute transporter; PC, phosphatidylcholine; PFIC2, progressive familial intrahepatic cholestasis, type 2; SLCO, solute carrier organic anion; TGR5, transmembrane G protein- coupled receptor 4; UDCA, ursodeoxycholic acid. 2 Abstract During the last 80 years there have been extraordinary advances in our knowledge of the chemistry and biology of bile acids. We present here a brief history of the major achievements as we perceive them. Bernal, a physicist, determined the x-ray structure of cholesterol crystals, and his data together with the vast chemical studies of Wieland and Windaus enabled the correct structure of the steroid nucleus to be deduced.
    [Show full text]
  • Konrad Emil Bloch Was Spread Upon the Permanent Records of the Faculty
    At a meeting of the FACULTY OF ARTS AND SCIENCES on May 1, 2018, the following tribute to the life and service of the late Konrad Emil Bloch was spread upon the permanent records of the Faculty. KONRAD EMIL BLOCH BORN: January 21, 1912 DIED: October 15, 2000 Konrad Bloch was an outstanding leader among biochemists, who unraveled the pathways of intermediary metabolism in living cells. When he received the 1964 Nobel Prize for medicine or physiology jointly with Feodor Lynen, their achievements were hailed for rendering “an outline for the chemistry of life [. .] plainly visible,” and ranked among “the great accomplishments of science in the 20th century.” Bloch was chiefly cited for his elucidation of the complex biosynthesis of cholesterol. During a 25-year odyssey, researchers traced the origins of each of the 27 carbons in the cholesterol molecule to one of two carbon atoms in acetic acid. Laboratories worldwide studied the roughly 36 reaction steps involved in the transformation of acetic acid to cholesterol, gaining insights into regulating enzyme activity when catalyzing the biosynthesis of cholesterol. Such studies led to the development of statins, drugs now widely used to reduce the risk of heart disease and stroke. This monumental saga of cholesterol biosynthesis still inspires many kindred projects, including investigations into the origin of life on this planet. Konrad was born in 1912 in Neisse, Germany, (now Nysa, Poland), into a highly cultured, prosperous Jewish family. After graduating from the local gymnasium, Konrad enrolled at Munich’s Technische Hochschule, in 1930. There, he intended to pursue engineering and metallurgy; instead, in a course by Hans Fischer, he became fascinated with organic chemistry.
    [Show full text]
  • On the Origin and Prevention of PAIDS (Paralyzed Academic Investigator's Disease Syndrome)
    On the origin and prevention of PAIDS (Paralyzed Academic Investigator's Disease Syndrome). J L Goldstein J Clin Invest. 1986;78(3):848-854. https://doi.org/10.1172/JCI112652. Research Article Find the latest version: https://jci.me/112652/pdf On the Origin and Prevention of PAIDS (Paralyzed Academic Investigator's Disease Syndrome) Presidential Address Delivered before the 78th Annual Meeting of the American Society for Clinical Investigation, Washington, D. C., 3 May 1986 Joseph L. Goldstein Departments ofMolecular Genetics and Internal Medicine, University of Texas Health Science Center at Dallas, Dallas, Texas 75235 In my Presidential address, I will depart from the traditional known medical school on the West Coast. His fellowship included philosophical discourse. Instead, I will take this occasion to de- one year of clinical duties and two years of research. During his scribe a newly recognized clinical syndrome. This devastating clinical year, J.R. was struck by how little was known about liver disease afflicts our brightest and most promising physician-sci- damage in patients with hepatitis and cirrhosis. He decided to entists, crippling them just when they should be maturing into spend the next two years studying liver regeneration. During the major investigators. The syndrome is called PAIDS-Paralyzed last year of his fellowship, J.R. made an exciting discovery. He Academic Investigator's Disease Syndrome. The recognition of found that a crude extract from newborn rat liver stimulates PAIDS, with its characteristic signs and symptoms, has come growth of the liver when injected into partially hepatectomized about as a result of my five years of service on the Council of rats.
    [Show full text]
  • Bloch Was Placed Upon the Permanent Records of the Faculty
    At a Meeting of the Faculty of Arts and Sciences on May 1, 2018, the following tribute to the life and service of the late Konrad Emil Bloch was placed upon the permanent records of the Faculty. KONRAD EMIL BLOCH Born: January 21, 1912 Died: October 15, 2000 Konrad Bloch was an outstanding leader among biochemists, who unraveled the pathways of intermediary metabolism in living cells. When he received the 1964 Nobel Prize for medicine or physiology jointly with Feodor Lynen, their achievements were hailed for rendering “an outline for the chemistry of life [. .] plainly visible,” and ranked among “the great accomplishments of science in the 20th century.” Bloch was chiefly cited for his elucidation of the complex biosynthesis of cholesterol. During a 25-year odyssey, researchers traced the origins of each of the 27 carbons in the cholesterol molecule to one of two carbon atoms in acetic acid. Laboratories worldwide studied the roughly 36 reaction steps involved in the transformation of acetic acid to cholesterol, gaining insights into regulating enzyme activity when catalyzing the biosynthesis of cholesterol. Such studies led to the development of statins, drugs now widely used to reduce the risk of heart disease and stroke. This monumental saga of cholesterol biosynthesis still inspires many kindred projects, including investigations into the origin of life on this planet. Konrad was born in 1912 in Neisse, Germany, (now Nysa, Poland), into a highly cultured, prosperous Jewish family. After graduating from the local gymnasium, Konrad enrolled at Munich’s Technische Hochschule, in 1930. There, he intended to pursue engineering and metallurgy; instead, in a course by Hans Fischer, he became fascinated with organic chemistry.
    [Show full text]
  • Yoshinori Ohsumi Tokyo Institute of Technology, Tokyo, Japan
    Molecular Mechanisms of Autophagy in Yeast Nobel Lecture, December 7, 2016 by Yoshinori Ohsumi Tokyo Institute of Technology, Tokyo, Japan. cience is a system of knowledge that is gradually accumulated over many S years by society, but it is also an inherently human activity. I believe that every scientist is a product of the era in which they live. So I’d like to start from a brief introduction of my life, and then give a historical overview of my scien- tic work. Early life I was born in Fukuoka, southern Japan, in 1945, half a year before the end of World War II. is was a very challenging time in Japan, and everyone had diculty getting basic daily necessities, including food. I myself suered from severe malnutrition and was a very sickly child. Around this time my mother got tuberculosis and spent a long period bed-bound, but she was miraculously able to recover thanks to a gi of just-developed antibiotics from a family friend in Hawaii. When I was about 8 years old, my mother was nally able to resume a normal life. My brother, Kazuo, who is 12 and a half years my senior, le home to enter the Faculty of Literature at the University of Tokyo as I began elemen- tary school. I was brought up through the eorts of my father and two sisters, Reiko and Junko, and many other people throughout what was a dicult time for our family. 277 278 The Nobel Prizes My childhood home was surrounded by nature, with rice paddies, streams, hills and the sea all nearby.
    [Show full text]