Lesions of meningoencephalitis were found in 55 per cent of 372 rabbits comprising the laboratory stock regarded as healthy, others with snuffles or dying from different affections while being kept under observation, and still others which were employed for experimental purposes, such as tumor transplantation and Treponema pallidum inoculation. None was injected intracerebrally. The lesions consist in the main of infiltration with mononuclear cells occurring around the blood vessels, in the meninges, in the cortex, and under the ependyma of the lateral ventricles, together with particular focal necrotic areas in the cortex. The incidence of these histopathological changes varies in different series of animals; in those supposedly normal and in rabbits inoculated with a transplantable tumor or with Treponema pallidum material, the percentage of positives was from 40 to 60; in those suffering from miscellaneous diseases, such as pneumonia, septicemia, etc., the percentage was 70, and in rabbits ill with snuffles, as many as 76 per cent were affected. Marked lesions were observed in 47.5 per cent of the total. The histopathological picture observed in these rabbits corresponds to those offered by a number of investigators as evidence of the transmission of certain nervous diseases of man to this animal. The accidental cerebral lesions in the rabbit, of a wide variety, and of frequent occurrence, are to be regarded as existing before any experimental procedure is begun. Their recognition is of the utmost importance in the interpretation of experimental results based on the presence of similar changes in this animal.

In 1920, Olitsky and Kligler separated the poison of Bacillus dysenterit Shiga into two physically and biologically distinct toxins. One, a true, soluble, exotoxin, an early product of the growth of this microorganism in vitro, is relatively heat-labile and yields an antiexotoxic immune serum. The other, an endotoxin, a product of the autolysis, or disintegration, of the bacillus with the resultant liberation of intracellular components, is heat-stable and is not neutralized by antiexotoxic serum. The exotoxin has a specific affinity for the central nervous system in the rabbit; the endotoxin, on the other hand, affects only the intestinal tract.Since the exotoxin arises in the early period of growth, and since the endotoxin results from bacterial disintegration-a factor difficult to control in growing cultures-there is great technical difficulty in preparing pure endotoxin or exotoxin directly from the Shiga bacillus. Olitsky and Kligler have indicated methods for their separation. In this paper we shall describe an additional method which we believe to be more simple and effective. In this way the previous dbservation that the toxins of this microorganism are distinct has been confirmed.It is relatively more simple to obtain pure neurotoxic exotoxin. Merely the filtrate of the early growths of Shiga bacilli, before bacterial disintegration occurs, suffices. Hence young, vigorously growing, well oxygenated cultures, incubated at 37 0 C. for from 1 to 3 or even to 5 or 7 days, depending on the rate of autolysis, or disintegration, when filtered through Berkefeld V or N candles, yield pure exotoxin in the bacteria-free ftiltrate. ' This is not the case, however, with 'Olitsky, P. K., and Kligler, I. J., J. Exp. Med., 1920, xxxi, 19. 767 onMay 9, 2018 jem.rupress.org Downloaded from http://doi.org/10.1084/jem.37.6.767 Published Online: 1 June, 1923 | Supp Info:TOXINS OF BACILLUS DYSENTERIE SHIGA endotoxin. The endotoxin which arises later as a result of bacterial dissolution is always admixed with the exotoxin which is first produced in the medium, and therefore the toxins require mechanical separation for purification. Suppression of Exotoxin by Anaerobiosis.If the exotoxic function of Shiga bacilli could be suppressed, the problem of producing pure endotoxin directly from disintegrated bacilli would be simplified. In seeking for a method for this suppression, use was made of the underlying principle of rapid and increased exotoxic production-oxygenation. Roux and Yersin, 2 by passing a stream of oxygen through the cultures or employing thin layers of culture fluid, determined the requirements for the prompt and effective production of diphtheritic soluble toxin-a method subsequently yielding successful results in the hands of Park and Williams 3 and accepted generally as a standard, not only for the diphtheritic exotoxin but also for that of other bacteria, including the Shiga bacillus. 4 If the converse held, that is, if Shiga bacilli were grown in an oxygenfree atmosphere and in a deep layered medium, t...

The experimental studies on the incitant of common colds in man to be reported in this paper were begun shortly after the investigations on influenza by Olitsky and Gates t~ were undertaken. They were initiated by the desire to check or control the latter studies and to determine, if possible, any causative agent in the nasopharyngeal secretions derived from persons suffering from common colds. This work has now extended over 4 years, and, while still incomplete, our purpose is to state only the results which we regard as established experimentally.

The typhus virus contained in the blood of guinea pigs at the height of the experimental disease remains infective for 31 days in collodion sacs placed within the abdominal cavity of guinea pigs.

is so definite and exact that I felt when he read this paper that a brief outline of his method of examination was of great importance. We all realize what pus infections will do in the accessory sinuses, but I feel confident that many of us do not realize the importance of a definite method of examination.Dr. C. A. Broaddus, Salt Lake City : I have not had very