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Chemotherapy of gonococcal infection has advanced markedly during the last decade. Sulfonamides appear to be less effective now, however, than when first introduced for the treatment of the disease. Two factors may be responsible for this evident decreased effi-*

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Serologically active substances have been isolated from the gonococcus as well as from the broth in which the organism has been grown, but as yet not all of them have been chemically defined. Several investigators (DeChristmas, 1897;Herrold, 1927;Clark, Ferry and Steele, 1931; and Wolifenstein and Pieper, 1931) have reported that broth in which the gonococcus has been grown elicits a typical dermal reaction in patients with gonococcal infection but not in persons without evidence of the disease. These findings have been interpreted as evidence that the gonococcus elaborates an immunologically active substance during growth in a broth medium. Recently, Rossett (1939), working with gonococcal bouillon filtrates, separated a fraction which possessed antigenic properties similar to those noted by previous workers. He considered this material to be a carbohydrate, a conclusion which was not supported by quantitative chemical proof.By fractionation procedures similar in a number of respects to those employed by Rossett, we have isolated a fraction from gonococcal broth supernatants which was antigenic and toxic for laboratory animals. The present report describes the isolation and properties of this fraction, which is proteic in nature. No evidence was found to indicate that we were dealing primarily with a carbohydrate.MATERIALS AND METHODS Preparation offraction Seven strains of Neisseria gonorrhoeae, which had been under artificial cultivation for from 1 month to 34 years, were selected for the study. The organisms were grown in 300-ml. flasks containing 100 ml. of Douglas's broth to which 0.5 per cent each of sodium phosphate and sodium nitrate had been added. After 3 days of incubation at 37°C. the cells were removed by centrifugation. The broth supernatants were concentrated ten-fold in vacuo at temperatures not exceeding 20°C., and the broth constituents of low molecular weight were then separated by dialysis in the cold. Small amounts of nucleoprotein were removed from the broth concentrate by precipitation at pH 4.5. The resulting supernatant, when brought to neutrality and dialyzed against 25-per cent alcohol I These studies were supported by a grant from the John andMary R. Markle Foundation. 2 This paper was presented in preliminary form at the 43rd Annual Meeting of the Society of American Bacteriologists,

This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under § 54 of the German Copyright Law where copies are made for other than private use, a fee is payable to the publlsher, the amount of the fee to be determined by agreement with the publisher. © by Springer-Verlag Berlin· Heidelberg 1975. Softcover reprint of the hardcover ist edition 1975 Library of Congress Cataloging in Publication Data (Revised) Main entry under title: Concepts in biochemical pharmacology. Handbuch der experlmentellen Pharmakologie. Handbook of experimental pharmacology. New series, v. XXVIII, 1, etc. Includes bibliographies. I. Drug metabolism-Collected works.!. Argy, W. P. II. Brodie, B. B., ed. III. Gillette, James R., 1928-ed. IV. Ackerman, Helen S., ed. V. Series: Handbuch der experimentellen Pharmakologle, v. XXVIII, 1 QP905.H3 Bd. 28, t. 1, etc. [RM301] 615'. 7 79-135957 ISBN 0-387-05134-1. The use of general descriptive names, trade names, trade marks, etc. in this pUblication, even if the former are not especially Identified, is not to be taken as a sign that such names, as understood by the Trade Marks and Merchandise Marks Act, may accordlngiy be used freely by anyone. PrefacePart 3 of the Handbook of Experimental Pharmacology (Concepts in Biochemical Pharmacology) applies the principles enunciated in Parts 1 and 2 to clinical pharmacology and toxicology. The major objective is to elucidate the many factors that determine the relationships between pharmacokinetic aspects of the disposition and metabolism of drugs and their therapeutic or toxic actions in man.Because of the more restricted information obtainable in human studies, this volume reflects the editors' bias that an understanding of pharmacokinetics is fundamental for assessing pharmacologic or toxicologic effects of drugs in humans. The first chapter is a unique primer on when to apply and how to use pharmacokinetic tools in human pharmacology. The second chapter explains the general assumptions underlying pharmacokinetic approaches both in simple terms for the novice and in mathematical form for the more sophisticated reader.Several chapters on determinants of drug concentration and activity discuss drug absorption, drug latentiation, drugs acting through metabolites, enterohepatic drug circulation, influence of route of drug administration on response, genetic variations in drug disposition and response, age differences in absorption, distribution and excretion of drugs, and pathologic and physiologic factors affecting absorption, distribution and excretion of drugs and drug response. The focus of these chapters is data obtained in human, rather than animal, studies. Most of the chapters contain new material never summarized previously.The section on drug interactions opens with a chapter in which all drug interactions are viewed as result...