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No specific diagnostic test for rheumatic fever has been available to date (1). The tryptophannicotinic acid metabolic series was studied exhaustively in the present work. This investigation was based on a previous observation that the tetrahydrofurfuryl ester of nicotinic acid elicited a different response in the skin of patients suffering from active rheumatic fever than in the skin of nonrheumatic patients (2). The reaction was attributed to nicotinic acid, a member of the tryptophan metabolic series.The present report describes an abnormal product of tryptophan metabolism isolated from the urine of rheumatic subjects. MATERIALS AND METHODSStudies in human subjects. Three groups of subjects were used in this study. The first two consisted of both male and female children between 3 and 16 years of age.Group I consisted of inpatients at the National Children's Cardiac Hospital with inactive rheumatic heart disease,' inactive rheumatic fever,' or congenital heart disease, and group II, of young subjects from other places who had either active or inactive rheumatic heart disease, or rheumatic fever. These two groups were considered separately because any uniform dietary and environmental effects observable among group I subj ects were balanced by dietary and environmental differences among group II subjects. Studies requiring large quantities of urine necessarily excluded group II patients. Group III consisted of adult male patients at the Veterans Administration Hospital, Coral Gables, Florida, with Hodgkin's disease or mutiple myeloma.Normal control subjects were also studied. As controls for groups I and II, urines were collected from local children of comparable ages and sex with no known diseases; as controls for group III, urine weas obtained from adult males with no known diseases.In all subjects, 24-or 48-hour urine samples were collected with toluene as a preservative and were refrigerated as soon as possible after collection. Urine specimens were * Supported by grants from the Florida Heart Association and the Heart Association of Greater Miami, Fla. ' In this report, "rheumatic heart disease" and "rheumatic fever" are distinguished by the presence or absence of heart involvement, respectively. analyzed for products in the tryptophan-nicotinic acid metabolic series.In some instances, "tryptophan loading" tests w,ere done. Five g of L-tryptophan suspended in 200 ml of orange juice was administered orally. The urinary excretion of 5-hydroxyindoleacetic acid and related compounds was measured during the subsequent 24 hours and compared with the amounts excreted over the same interval on the previous day, when only orange juice was fed.Chemical analytical mtiethods. Tryptophan was determined by the p-dimethylaminobenzaldehyde method of Spies and Chambers (3). Indoxylsulfate and tryptamine were determined by use of a modified Ehrlich's reagent (4). Kynurenic acid and xanthurenic acid were measured by the fluorometric method of Satoh and Price (5). Kynurenine was converted to o-acetophenone, which wvas measu...

Dental caries is the most common disease affecting mankind today. Its economic toll in the United States alone amounts to several billion dollars. To this must be added its toll in pain, loss of working time, and psychological distress.Despite the prevalence of this affliction and the amount of investigation it has engendered, its etiology remains obscure. In the past, many different microbial organisms have been indicted as the causative factor of the pathologic state. Among these, lactobacilli and streptococci enjoy favored positions.'-'In 1955, Orland, Blayney, Harrison, Reyniers, Trexler, Ervin, Gordon, and Wagner6 produced experimental dental caries by monoinoculating germfree rats with a particular strain of streptococcus. Subsequently, Fitzgerald, Jordan, and Stanley7 confirmed these findings in germfree rats, and Fitzgerald and Keyes8 have established the etiologic role of streptococci in hamster caries. Of a variety of organisms tested, only the specific streptococci were cariogenic. Their findings also disclosed a host specificity in the organisms, i.e., the rat strains produced caries only in the rat and not in the hamster, and the hamster strains produced caries only in the hamster and not in the rat. This specificity for the host and not for the tissue prompted the present investigation of the characteristics and methods of identification of these organisms. These studies of animal strains may provide clues for investigation of the bacterial etiology of human caries.Materials and Methods STREPTOCOCCAL GROUPING.-Streptococci have been separated into groups based on the presence of an immunologically distinct carbohydrate in the cell wall of the organisms.9-12 Cariogenic and non-cariogenic streptococci (hamster and rat strains) were provided by Dr. Robert Fitzgerald of the National Institute of Dental Research. As a preliminary step in the identification of cariogenic organisms, their reactivity with appropriate streptococcal antisera was tested to determine whether they belonged to any of the known groups of streptococci. The organisms were grown in 40-ml. quantities of Todd-Hewitt broth, and acid extracts were prepared by the method of Lancefield.9 These extracts have been used in microprecipitin tests'3 with group-specific streptococcal antisera, Groups A through S * PREPARATION OF ANTISERA.-As a further step in establishing the identity of cariogenic streptococci and to determine whether they belonged to a homogeneous group, antisera were prepared using rat (FA) and hamster (HS) strains as vaccines. Each of the two strains of cariogenic streptococci was grown in one liter of ToddHewitt broth supplemented with 0.5 per cent lactalbumin hydrolysate. The cultures were heat-killed at 560 C. for one hour and then divided into three parts for the preparation of three different types of vaccine: 1. A vaccine was prepared from whole organisms suspended in physiological saline

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S have demonstrated that nutrient broth irradiated with ultra-violet light prior to inoculation of Staphylococcus aureus induces mutation in this organism. The rate of mutation of S. aureus to penicillin and streptomycin resistance and to inability to ferment mannitol can be increased by this method of indirect treatment of the bacterium with ultra-violet light.The discovery of the effect of irradiated medium upon bacteria has opened up a new avenue of attack upon the problem of induction of mutation and possibly mutation itself. It would be of some interest therefore, to extend this method of treatment to an organism other than Staphylococcus, preferably one in which a sexual cycle is easily demonstrated so that the mutations which are derived can be shown to fulfill the more conservative definitions of a mutation. The organism should also be one in which the gametes are easily exposed to a medium containing chemical compounds with a relatively short lifetime, and which lends itself to the analysis of mutation rates. Neurospora was chosen as the test organism because of its easily controlled sex cycle, and the fact that the gametic nuclei are easily exposed to treatment with chemicals just as are the cells of a bacterium.I n addition to testing the effects of irradiated medium on Neurospora, experiments were also performed using hydrogen peroxide and potassium cyanide. WYSS, have reported results which indicate that hydrogen peroxide may play an important role in the effect of the irradiated medium on the mutation rate. If this is so, then one might expect cyanide to be effective, since it is a known inhibitor of the hydrogen peroxide decomposing enzyme, catalase. Theoretically, poisoning the catalase should permit the peroxide concentration in the cell to build up to a higb enough level to have a mutagenic effect. GENERAL METHODS AND MATERIALSThe wild type strains of Neurospora crassa used in all of these experiments were derived from single ascospore cultures obtained from a cross between Emerson wild types 5297a and 5256A. All irradiation was done with a Hanovia double-U, SC-2537 ultra-violet mercury vapor lamp operating a t 120 milliamperes. The material was irradiated a t a distance of 15 cm from the lamp.Difco nutrient broth such as used in experiments described by STONE