The Journal of Experimental Medicine

Coburn, Alvin F.; Haninger, Joan

doi: 10.1084/jem.99.1.1pmid: 13118059

The passive Arthus arthritis in the guinea pig provides an experimental model for studying reactions comparable to those which occur in rheumatic fever. The joint swelling in the Arthus reaction is followed by tissue injury which is reflected 24 hours later by a rise in the DPA level. The height of this rise is determined by the degree of injury, which in turn is determined both by the strength of the antibody injected and also by the number of antigen depots created. The swelling reaction and the DPA rise can be suppressed by sodium salicylate, cortisone, or splenin A. The amount of drug required to block a DPA rise (DPA unit) is approximately tenfold the amount required to inhibit the joint swelling by 50 per cent (Arthus unit). Even when the Arthus arthritis has completed the swelling phase, treatment with appropriate amounts of these drugs suppress a rise in DPA. It was pointed out that the DPA rise appears to be associated with the tissue injury that follows joint swelling; that the degree of a DPA rise is determined by the severity of the inflammatory process; and that the amount of an anti-inflammatory agent required to suppress a DPA rise depends on the intensity of the reaction. Footnotes Submitted: 8 June 1953

Dalldorf, Gilbert; Gifford, Rebecca

doi: 10.1084/jem.99.1.21pmid: 13118060

Gravid mice become progressively more susceptible to infection with the pancreatic line of Group B-1 Coxsackie virus during the last week of pregnancy. A Group A-8 strain did not have such an effect. The young that survive despite the fact that their mothers are infected with a B-1 strain appear to be normal in the gross and microscopically, to grow at the usual rate, to be free of demonstrable virus, and to be susceptible on challenge with a homologous strain. Footnotes Submitted: 11 August 1953

Opie, Eugene L.

doi: 10.1084/jem.99.1.29pmid: 13118061

Depression of the melting point of liver tissue rapidly frozen by liquid nitrogen during life provides a means by which the molecular concentration within liver cells may be compared with that of solutions of sodium chloride or of blood or of blood serum. The rising temperature of frozen blood of guinea pig under the conditions of these experiments is retarded when melting occurs, pursues when plotted a prolonged linear course, and finally rises precipitously at –0.54°C. when melting is complete. With the melting of blood serum of guinea pig and of blood of cat and of rat, the temperature takes approximately the same course. The temperature changes are nearly the same as those of a frozen solution of sodium chloride isotonic with blood serum. The temperature changes of frozen liver assumes when plotted a linear course at about –1.1°C., increases at intervals with step-like progress and finally rises precipitiously at –0.76°C. The temperature changes in melting liver of cat and of rat are similar. The melting of liver begins at a level which approximates that of a solution of sodium chloride isotonic with it. The step-like course of temperature changes which occur during the melting of frozen liver are best explained by the assumption that the cells contain substances which successively and temporarily retard the rise of temperature. Footnotes Submitted: 27 September 1953

Fredrickson, Donald S.; Loud, Alden V.; Hinkelman, Beverly T.; Schneider, Henny S.; Frantz, Ivan D.

doi: 10.1084/jem.99.1.43pmid: 13118062

The effect on cholesterol synthesis of ligation of the common bile duct was studied in the rat. The bile ducts of rats were ligated; 24 to 48 hours later, estimates of the rate of cholesterol synthesis were made, either by injection of labelled water or acetate into the intact animal, or by incubation of slices or homogenates of the liver in the presence of 1-C 14 -acetate. These various criteria all indicated that cholesterol synthesis was increased following ligation of the bile duct. The average ratios of the rate of synthesis in the experimental animals to that in the controls were as follows: 1. Synthesis from C 14 -carboxyl-labelled acetate: ( a ) in the intact rat fed ad libitum , 19; ( b ) in liver slices from the fasted rat, 23; ( c ) in liver slices from the rat fed ad libitum , 4; ( d ) in cell-free homogenates from the fasted rat, >27; ( e ) in cell-free homogenates from the rat fed ad libitum , 17. 2. Synthesis from tritium-labelled water in the intact rat fed ad libitum , 4. Footnotes Submitted: 13 August 1953

Dubos, René J.; Hirsch, James G.

doi: 10.1084/jem.99.1.55pmid: 13118063

A stable, water-soluble substance which possesses potent antimycobacterial activity under certain conditions in vitro has been prepared from calf thymus. This substance has been tentatively named thymus peptide. In final concentrations of 1 to 10 µg. per ml. of an albumin medium it inhibits the growth of various strains of mammalian mycobacteria, but manifests only little or no inhibitory activity against a variety of other microbial species. The ability of thymus peptide to inhibit the multiplication of tubercle bacilli diminishes when the inoculum is large, or when the medium is acidic. It is also markedly antagonized by addition of enzymatic hydrolysate of casein or beef heart infusion broth to the culture medium. Thymus peptide does not exert a rapid bactericidal action on tubercle bacilli, but organisms exposed to this compound for longer than 2 weeks could not be made to multiply in ordinary culture media. Substances similar or identical to the thymus peptide preparation could be extracted from calf spleen, sheep thymus, beef lymph nodes, and calf pancreas, but not from calf lung or calf liver. Footnotes Submitted: 25 August 1953

Hirsch, James G.; Dubos, René J.

doi: 10.1084/jem.99.1.65pmid: 13118064

A substance possessing antimycobacterial activity under certain conditions in vitro has been prepared from aqueous extracts of calf thymus. Chemical studies have demonstrated that the activity of this substance is due to a basic peptide or a mixture of basic peptides. Although this thymus fraction has been shown to be essentially free of compounds other than peptides, it has not been obtained in a homogeneous state. The thymus peptide preparation is soluble in water and in the lower alcohols. Its solubility is minimal between pH 10 and 11, suggesting that its isoelectric point may be in this vicinity. The microbiological activity of thymus peptide is destroyed by acid or alkaline hydrolysis and also by trypsin digestion, but is unaffected by pepsin digestion. Cellulose membranes are permeable to thymus peptide. The most noteworthy finding concerning the amino acid composition of thymus peptide is the preponderance of the basic amino acids lysine and arginine, which together account for about 40 per cent of the weight of this substance. No cystine, and only trace amounts of other amino acids containing sulfur, are present in the thymus peptide preparation. Footnotes Submitted: 25 August 1953

Hirsch, James G.

doi: 10.1084/jem.99.1.79pmid: 13118065

The antimycobacterial activity of thymus peptide under certain conditions in vitro can be partially neutralized by increasing the concentration of sulfate ions in the medium, and to a lesser extent by the addition of certain organic compounds which contain sulfur. It is suggested that thymus peptide suppresses the growth of tubercle bacilli by interfering with the normal sulfur metabolism of these microorganisms. Polylysine peptide and pituitary adrenocorticotropic hormone, other basic peptides derived from animal tissues, also inhibit the multiplication of tubercle bacilli in vitro , and their antimycobacterial activity is also antagonized by sulfate ions. Basic peptide hormones prepared from the posterior pituitary gland do not affect the growth of acid-fast bacteria under the conditions of the test. Footnotes Submitted: 25 August 1953

Kass, Edward H.; Lundgren, Marguerite M.; Finland, Maxwell

doi: 10.1084/jem.99.1.89pmid: 13118066

Cortisone acetate, hydrocortisone, and hydrocortisone acetate depress the resistance of mice to pneumococcal and influenza viral infections, although hydrocortisone acetate is somewhat less effective than the free alcohol, when given subcutaneously. Pituitary adrenocorticotropin, even in highly purified form and in oil and beeswax, does not significantly alter the resistance of mice to these experimental infections, even when given in doses which may cause profound eosinopenia, lymphopenia, and weight loss, and which are at the limit of tolerance of the animals. Corticosterone depresses resistance to pneumococcal infections significantly, but fails to alter resistance to influenza viral infections. The findings suggest that murine adrenals may produce one of the known adrenal steroids such as corticosterone along with another steroid, or may produce a steroid other than cortisone, hydrocortisone, or corticosterone. When resistance is decreased by adrenal steroids, survival time is invariably shortened, and the effect of the steroid hormones is frequently demonstrable within the 1st day after infection with pneumococci, making it unlikely that the depression of resistance that is seen is primarily due to depression of antibody formation. A single dose of 5 mg. of cortisone may cause depression of resistance and may decrease the survival time for 3 to 6 days afterward. Growth hormone (somatotropic hormone) in highly purified form, and in the doses used, did not overcome the weight loss induced by cortisone, but the animals treated with growth hormone and cortisone regained their lost weight more rapidly than those receiving cortisone alone. Growth hormone alone caused a slight increase in the rate of gain in weight over controls. Growth hormone alone did not increase resistance to infection, and did not increase the survival time, in mice infected with either pneumococci or influenza virus. Growth hormone in various dosages failed to overcome the effect of cortisone in depressing resistance to these infections. Cortisone, hydrocortisone, corticosterone, and corticotropin did not alter significantly the titers of influenza virus attained in the murine lungs during the first 2 days after infection, but cortisone and hydrocortisone markedly delayed the rate at which virus titers declined during the subsequent 6 days. Corticosterone and corticotropin delayed the rate at which the titers declined but slightly, and growth hormone had no apparent effect, as compared with controls. Growth hormone did not overcome the effect of cortisone and hydrocortisone on viral titers. No detectable antibody was found as late as 6 days after infection, in controls or in hormone-treated animals. Footnotes Submitted: 3 August 1953