The Journal of Experimental Medicine

Shwartzman, Gregory

doi: 10.1084/jem.54.1.1pmid: 19869894

It has proved possible to elicit passive immunity to B. typhosus reacting factors by means of normal and immune homologous neutralizing antibodies. The in vivo serum protection against these factors followed the law of multiple proportions. There was observed a considerable loss of antibodies from the blood stream. Passive immunity was best obtained when the immune serum was injected intravenously ½ hour before the intravenous injection of the reacting factors. It was possible to prevent the occurrence of the local skin reaction by an intravenous injection of serum after the intravenous injection of the reacting factors, provided the serum dose was very large and provided the serum injection was made immediately after the filtrate injection. A number of experiments clearly demonstrated the interesting fact that the greater the amount of antiserum injected intravenously, the more efficient was the in vivo neutralization, in a ratio distinctly greater than the quantitative increase of serum. It is suggested that there may be a practical value of the observation in relation to serum therapy. The results also demonstrated passive serum protection against the lethal effect of B. typhosus "agar washings" filtrates, in a ratio which seemed to suggest the law of multiple proportions. Footnotes Submitted: 26 March 1931

Zinsser, Hans; Castaneda, M. Ruiz

doi: 10.1084/jem.54.1.11pmid: 19869896

Mexican typhus virus can be passed through ticks by the method of rectal injection. The virus will remain alive in the ticks for at least 12 days. These studies, together with one of our preceding publications and the work of Dyer, demonstrate that there are at least three insects—bedbugs, fleas and ticks—which must be considered as possibilities in conveying typhus fever from an animal reservoir to man. Our work will be continued by a study of rats and mice caught in typhus regions such as Mexico City and its immediate vicinity, with a search for the virus in these rodents as well as an analysis of the insects found upon them or in the localities in which they are concentrated. Footnotes Submitted: 31 March 1931

Rake, Geoffrey; McEachern, Donald

doi: 10.1084/jem.54.1.23pmid: 19869899

A study has been made of the pathological changes in the hearts and other tissues of animals rendered hyperthyroid with thyroxine. Forty-four rabbits and seventeen guinea pigs were given intramuscular injections of thyroxine every other day and sacrificed at varying intervals. Tissues from a series of normal animals (twenty guinea pigs and forty-three rabbits) were examined as a control. The changes in the heart and other tissues of hyperthyroid animals were insignificant and varied but little from changes seen in normal control animals. Of eight thyrotoxic guinea pigs that developed coincidental infection ( bronchisepticus ) all showed myocardial lesions. Of nine thyrotoxic guinea pigs, free of infection, only one gave evidence of myocardial change. It is pointed out that hyperthyroidism, per se , cannot be held responsible for these lesions, which would appear to have been associated with the infection. It was noted that rigor mortis of the skeletal muscles occurred much sooner in the bodies of hyperthyroid animals than in normal animals. Footnotes Submitted: 10 March 1931

Olitsky, P. K.; Knutti, R. E.; Tyler, J. R.

doi: 10.1084/jem.54.1.31pmid: 19869900

1. Conjunctival tissue derived from alien and native American white persons in New York City, having trachoma in an advanced stage, has been used successfully to induce in Macacus rhesus monkeys characteristic granular conjunctivitis. The transfer of infection was effected either by a single subconjunctival injection, or by repeated swabbing with conjunctival secretions. 2. Pathogenic strains of Bacterium granulosis have been recovered from the trachomatous tissues of six out of eleven patients. In addition, the organisms have been isolated from the monkeys infected with human material. 3. Repeated swabbing with secretions obtained from monkeys having experimental trachoma has given rise to characteristic granular conjunctivitis in normal animals. In addition, repeated instillations of suspensions of conjunctival tissue fragments derived from affected monkeys have led to characteristic infection of the conjunctivae of normal monkeys. 4. Contact infection occurs in monkeys, as it has long been known to occur in human beings; animals with smooth conjunctivae developing the experimental disease when merely caged with infected monkeys. 5. Repeated instillation of cultures followed by rubbing the eyelids will lead to the disease in monkeys, a method of transfer which indicates one manner in which the affection may be transmitted from man to man. Yet another manner of producing the experimental condition is by repeated swabbing with cultures of Bacterium granulosis . Noguchi has already reported the successful outcome of the subconjunctival inoculation of cultures and the spread of the disease from an infected conjunctiva to the other eye of the same animal. 6. Tissues derived from cases of human trachoma or from monkeys having the experimental disease induce, on conjunctival inoculation of Macacus rhesus monkeys, the same clinical and pathological effects as do cultures of Bacterium granulosis . The conjunctival lesions closely resemble, in clinical appearance and in microscopic changes, those of the follicular stages of trachoma in man. Footnotes Submitted: 17 March 1931

Rhoads, C. P.; Goodner, Kenneth

doi: 10.1084/jem.54.1.41pmid: 19869901

1. The pathology of the experimental dermal pneumococcic infection in the rabbit is described in detail and the findings are compared with the histological alterations seen in the human pneumonic lung. There would appear to be a basic similarity of the lesions in both tissues. 2. A copious production of edema fluid is the outstanding characteristic of the early lesion. It occurs prior to any significant cellular change. In the spreading lesion an infiltration of the tissues with fluid precedes any other sign of reaction between tissue and microorganism. It seems likely that the advancing fluid carries with it the infecting organisms and inoculates all tissues which it reaches. The resulting infection seems not to take place by an active invasion of microorganisms but by a progressive inoculation from an infected fluid. Footnotes Submitted: 30 March 1931

Dubos, René; Avery, Oswald T.

doi: 10.1084/jem.54.1.51pmid: 19869902

1. An organism has been isolated from peat soil which decomposes the specific capsular polysaccharide of Type III Pneumococcus. 2. The isolation has been made possible by the use of a synthetic mineral medium containing the specific polysaccharide as sole source of carbon. By repeated transfers in this medium the potential capacity of the organism to decompose the specific substance has been progressively increased. 3. The organism is a pleomorphic bacillus, motile and spore-bearing, exhibiting metachromatic granules; its reaction to the Gram stain varies according to the medium on which it is grown. It is strictly aerobic and grows well in plain broth and peptone solutions; it does not produce gas in any media and it forms small amounts of acid only on dextrin, galactose, lactose, salicin, and trehalose; its growth is inhibited by glucose. 4. The organism decomposes the capsular polysaccharide of Type III Pneumococcus aerobically, between pH 6.2 and 7.8, at room temperature and at 37.5°C., but not at 54°C. The decomposition of the specific substance is inhibited by the presence in the medium of other nutrients, such as peptones, which act as a more readily available source of energy. The action of the organism is specific; it does not attack the soluble specific substance of Type I or Type II Pneumococcus, nor any of the other bacterial polysaccharides thus far tested. 5. The organism possesses an endocellular enzyme. This enzyme has been extracted by autolysis of the bacterial cells; in sterile solution it exhibits the same specific action as do the organisms from which it is derived, decomposing only the capsular polysaccharide of Type III Pneumococcus. 6. This enzyme decomposes the Type III specific polysaccharide under anaerobic as well as under aerobic conditions; it is inactivated at 60–65°C.; the rate of decomposition of the specific substance is not affected by the presence of normal serum. 7. There exists a quantitative relationship between the total amount of specific substance decomposed and the amount of enzyme preparation used; the existence of this relation makes it possible to express the activity of a given enzyme preparation in terms of the minimal amount required for the complete decomposition of a given amount of specific substance. 8. The specific decomposition of the capsular polysaccharide of Type III Pneumococcus, by the organism as well as by the enzyme it produces, illustrates once more the specificity of the types of Pneumococcus and confirms the fact that the capsular polysaccharides, and not some impurities carried along with them, are responsible for type specificity. Footnotes Submitted: 25 March 1931

Avery, Oswald T.; Dubos, René

doi: 10.1084/jem.54.1.73pmid: 19869903

The bacterial enzyme which decomposes the purified capsular polysaccharide of Type III Pneumococcus in vitro also destroys the capsules of the living organisms growing in media and in the animal body. Potent preparations of this same enzyme protect mice against infection with virulent Type III Pneumococcus. The protective action is type-specific. The protective activity of the specific enzyme is destroyed by heat (70°C. for 10 minutes). The enzyme remains in an effective concentration 24 to 48 hours after its injection into normal mice. The enzyme has been found to exert a favorable influence on the outcome of an infection already established at the time of treatment. A definite relationship has been found to exist between the activity of the enzyme in vitro and its protective power in the animal body. The mechanism of the protective action is discussed with special reference to the relation between the decapsulation of the bacteria by the enzyme and the phagocytic response of the host. Footnotes Submitted: 25 March 1931

Rivers, T. M.; Berry, G. P.; Sprunt, D. H.

doi: 10.1084/jem.54.1.91pmid: 19869904

1. The virus of psittacosis is present in the nasal secretions, feces, blood, spleen, and liver of an infected parrot. 2. Parrots are susceptible to intraoral, intranasal, or intramuscular inoculations of the virus. 3. The most constant pathological changes produced by psittacosis in parrots occur in the spleen and liver. The lesions exhibited in the latter organ consist of areas of necrotic liver cells and damage to bile ducts. In no instance, in our experience, were lesions observed in a parrot's lungs comparable to those found in the lungs of men. 4. "Minute bodies" similar to those described by Levinthal and others were found in many, but not in all of the infected birds. 5. Parrots that have recovered from one attack of psittacosis exhibit an active immunity against reinfection. Footnotes Submitted: 31 March 1931

Rivers, T. M.; Berry, G. P.

doi: 10.1084/jem.54.1.105pmid: 19869895

The work presented in this communication concerning psittacosis in mice confirms Krumwiede's observations that mice inoculated intraperitoneally with emulsified livers and spleens containing the virus develop the disease and that the malady can in this way be passed serially through a number of mice. Furthermore, it has been shown that mice are susceptible to the virus administered intracerebrally and that the active agent can be propagated indefinitely by means of brain to brain inoculations. Moreover, by the use of mice, the presence of the virus of psittacosis in the sputum of a patient with the disease has for the first time been demonstrated. It follows that the mouse is available for diagnostic purposes. The pathological findings in infected mice consist of enlarged fatty livers that frequently show areas of necrosis infiltrated with polymorphonuclear and mononuclear cells; enlarged spleens with areas of necrosis and cellular infiltrations involving the pulp and lymphoid follicles; and, finally, in intracerebrally infected animals, a meningoencephalitis. The "minute bodies" described by other observers were not found in all animals, but they were seen with sufficient frequency in smears of peritoneal and meningeal exudates and in smears and sections of livers and spleens to demand serious consideration as the possible etiological agent of the disease. Neutralizing and protective antibodies were not found in convalescent human sera when the mouse was used as the test animal. Footnotes Submitted: 31 March 1931

Rivers, T. M.; Berry, G. P.

doi: 10.1084/jem.54.1.119pmid: 19869897

1. Rabbits and guinea pigs are susceptible to psittacosis virus introduced intracerebrally. By means of brain to brain passages in these animals the active agent is capable of propagation indefinitely. 2. Serial passages of the virus through rabbits and guinea pigs do not cause the active agent to lose its pathogenicity for parrots and mice. 3. The chief clinical evidences of infection in rabbits and guinea pigs following intracranial inoculation of the virus are fever and loss of weight. The pathological changes are characterized by a mild meningo-encephalitis, and fatty degeneration, focal necrosis, and infarction of the liver. 4. Rabbits upon recovery from an attack of psittacosis are actively immune. 5. Two strains of virus, human and parrot, were found to be immunologically similar. 6. No evidence was obtained to show that human convalescent serum possesses an appreciable amount of neutralizing substances. Footnotes Submitted: 31 March 1931