The Journal of Experimental Medicine

Harford, Carl G.; Hara, Mary

doi: 10.1084/jem.91.3.245pmid: 19871702

Pulmonary edema is a component of the fully developed influenza viral lesion in the mouse. Mice with experimental pulmonary fluid have an increased susceptibility to inhaled pneumococci and under these circumstances the organisms grow in the lung and produce the lesion of bacterial pneumonia. The presence of pulmonary edema in the lesion due to the influenza virus in the lung of the mouse appears to account adequately for the previous observation that inhaled pneumococci grow in the influenza viral lesion. Mice dying of pneumococcal septicemia after inhaling fine droplets containing this organism do not have pneumonia. The delay in migration of polymorphonuclear leucocytes into the lung after injection of pneumococci suspended in serum is an important factor in susceptibility to infection since it allows ample time for pneumococci to grow in the pulmonary fluid. The slow phagocytic action of pulmonary macrophages likewise permits growth of pneumococci. Conditions in human beings that are known to be complicated by pulmonary edema are also known to be associated with increased susceptibility to secondary bacterial pneumonia. Footnotes Submitted: 11 November 1949

Dubos, René J.; Fenner, Frank

doi: 10.1084/jem.91.3.261pmid: 19871703

Diffuse, submerged growth of BCG bacilli has been obtained in liquid media containing 0.02 per cent Tween 80 and the soluble fraction of human serum heated under acid conditions (pH 2.5) at 65°C. In the absence of glucose or glycerine,—which had a detrimental effect on viability—these cultures consisted predominantly of cells that were living and that remained viable during prolonged storage at temperatures ranging from 4 to 37°C. Footnotes Submitted: 16 November 1949

Fenner, Frank; Dubos, René J.

doi: 10.1084/jem.91.3.269pmid: 19871704

Groups of guinea pigs were vaccinated by the intracutaneous route with cultures of BCG grown in a liquid medium containing Tween 80 and the soluble fraction of heated human serum. After the cultures had been stored at 4°C. for various periods of time, the antigenic response was compared with that of another group of guinea pigs receiving standard BCG vaccine prepared by the conventional technique. The local lesions occurring at the site of injection of cultures in Tween-serum filtrate medium were more severe than those produced by the standard vaccine. It was shown that this difference was probably due to the much larger number of viable bacilli in the former preparations. A marked degree of sensitization could be produced with culture dilutions containing as few as 10 viable units (single bacilli or small clumps). Slightly larger doses of BCG led to the highest degree of tuberculin allergy detectable by the technique employed. Further increases in the dose of vaccine failed to alter the level of sensibility when the animals were tested with tuberculin 5 weeks after vaccination. The same degree of sensitization was achieved by vaccination with 0.1 cc. of either the standard vaccine or any of the fresh or stored cultures in Tween-serum filtrate medium. It was shown that these doses contained numbers of living bacilli far greater than the minimal number required to induce maximal sensitization. Under the conditions used, the guinea pigs vaccinated with cultures of BCG (fresh or stored) grown in the Tween-serum filtrate medium exhibited a marked degree of resistance to subcutaneous infection with virulent tubercle bacilli. Footnotes Submitted: 16 November 1949

Opie, Eugene L.

doi: 10.1084/jem.91.3.285pmid: 19871705

As shown in a previous paper the cells of the liver and of the kidney maintain an osmotic pressure approximately twice that of blood and of erythrocytes, exceeding this slightly in the case of liver and being slightly less in that of kidney. When liver cells are injured by chloroform or by carbon tetrachloride the osmotic pressure they maintain falls to the level of the medium that surrounds them but is promptly restored when recovery from the injury, with some regeneration of liver cells, occurs. When nephrosis is caused by potassium chromate or by chloroform the osmotic pressure maintained by parenchymatous cells of the renal cortex falls to that of the medium about them but returns to its normal level with recovery from the injury. Footnotes Submitted: 29 November 1949

Rammelkamp, Charles H.; Hezebicks, Margaret M.; Dingle, John H.

doi: 10.1084/jem.91.3.295pmid: 19871706

Three staphylococcal coagulases termed I, II, and III were differentiated by measuring the antibody titer of human sera. Coagulases I and II are antigenically distinct; coagulase III appears to be related to both coagulases I and II. These results were confirmed by specific neutralization experiments. These observations emphasize the importance of employing the correct type of coagulase in studying the role of this substance in the pathogenesis of staphylococcal infections. Preliminary observations in animals indicate that specific anticoagulase develops following induced infections. The role of this antibody in the recovery mechanism remains to be determined. Footnotes Submitted: 17 November 1949

Nelson, John B.

doi: 10.1084/jem.91.3.309pmid: 19871707

An outbreak of conjunctivitis, unaccompanied by involvement of the respiratory tract, is reported in a colony of white mice. A special strain of pleuropneumonia-like organisms was regularly isolated from the eyes and nasal passages of affected mice but not from the lungs or middle ears. Ocular carriage of these organisms in the absence of an inflammatory reaction occurred in at least 50 per cent of the adult mice. Transmission to the young was presumably initiated by parental contact, the organisms being recoverable after the eyes were open, and was continued after weaning by direct contact between cage mates. These organisms were repeatedly established on the conjunctiva of normal Swiss mice by direct contact with infected animals and subsequently maintained there for ten successive passages. Multiplication of the pleuropneumonia-like organisms, which was largely limited to the eye and its appendages, was accompanied by a low rate of conjunctivitis. The multiple conjunctival instillation of ocular washings from infected mice was the only additional method of implantation of the organisms which was successful. Footnotes Submitted: 6 December 1949

Blumenthal, Herman T.; Greiff, Donald; Pinkerton, Henry; DeWitt, Robert

doi: 10.1084/jem.91.3.321pmid: 19871708

Groups of embryonated eggs infected with the PR8 strain of influenza virus A were incubated at 34°, 37.5°, and 40°C. At frequent intervals, for periods ranging up to 96 hours, pooled allantoic fluids were tested simultaneously for infectivity and hemagglutination. After about 12 hours of virus growth, fluids often showed infectivity titres greater than 10 –5 , but were incapable of causing hemagglutination. At later time intervals, marked disagreement between the two tests for viral activity was noted at all temperatures, but most strikingly at 40°C. Hemagglutination titres were highest and best sustained in eggs incubated at 34°C., while incubation at 37.5°C. resulted in the highest and best sustained infectivity titres. Hemagglutination titre determinations do not reflect accurately the rate of influenza virus multiplication. Possible reasons for the lack of correspondence between hemagglutination and infectivity are discussed. Footnotes Submitted: 18 November 1949

Pinkerton, Henry; Greiff, Donald; Blumenthal, Herman T.; Hensley, Richard

doi: 10.1084/jem.91.3.331pmid: 19871709

In addition to the cycles of growth shown by the influenza A virus during the first 24 hours of its residence in the fertile egg, cycles separated by longer time intervals have been noted between the 24th and 96th hours. These longer cycles are best seen when the eggs are incubated at 40°C. Corresponding fairly accurately with these cycles of growth of the virus, wide cyclic variations in the rates of increase in oxygen consumption of the infected eggs have been found to occur. These variations are in striking contrast to the uniformity of increase noted in uninfected eggs. The variations in infectivity may be caused by periodic interference with virus multiplication by accumulated inactive virus particles. The variations in oxygen consumption probably are correlated with variations in the concentration of virus toxins. Footnotes Submitted: 18 November 1949

Greiff, Donald; Blumenthal, Herman T.; Pinkerton, Henry

doi: 10.1084/jem.91.3.335pmid: 19871710

Allantoic fluid from embryonated eggs infected with influenza A virus contains a toxic agent which can be demonstrated and quantitatively measured by its rapid effect on oxygen consumption when it is introduced in new series of fertile eggs. The effects were measured 90 minutes after the injection of the infected fluid, and were seen following both intra-allantoic injection and injection into the yolk sac. This toxin, in concentrations resulting from the injection of 0.5 cc. or less of the infected fluid, has no effect on oxygen consumption. The injection of 0.75 to 2.0 cc. of the fluid strikingly increases the oxygen consumption of the fertile eggs, while the injection of 3.0 cc. markedly depresses respiration. A similar reversal and eventual loss of the effect of the toxin on respiration were noted when the concentration of toxin was progressively diminished by heat inactivation. The toxic agent is slowly inactivated by heating at 56°C., but is effective long after infectivity and hemagglutinating ability have been destroyed. In this respect the agent differs from rickettsial and lymphogranuloma venereum virus toxins. The method described may be of value in studying the physiological effects of other toxic agents. Footnotes Submitted: 18 November 1949