Peter K. Olitsky

Simple method for enhancing development of acute disseminated encephalomyelitis in mice.

Conclusion By manipulations here described it was possible to induce acute disseminated encephalomyelitis in mice in a shorter time than heretofore, with fewer inoculations and with uniform response. The improved method consists of the intraperitoneal injection of H. pertussis vaccine followed by 2 spaced intracutaneous injections of proteolipide A + B prepared in a Freund-type adjuvant.

Acute disseminated encephalomyelitis produced in mice by brain proteolipide (Folch-Lees).

Conclusion Proteolipide A and B of Folch and Lees, a new group of lipoproteins, are capable of bringing about in mice acute disseminated encephalomyelitis indistinguishable from the affection induced by inoculation of whole brain tissue. The substance contains practically all of the encephalitogenic agent present in brain.

A Complement-Fixation Test for Poliomyelitis Virus.

Summary The results of experiments here reported show that the MEFl, a Lansing type of poliomyelitis virus, can be adapted to infant mice in which the virus develops an LD50 titer in excess of that found, as a rule, in adult mice. In the medium of newborn mouse brain, and in such an increased titer, the virus now lends itself to the preparation of a suitable antigen for specific and reproducible complement fixation.

Relative Susceptibility of various Stocks of Mice to Experimental Disseminated Encephalomyelitis.

Summary 1. The stock from which the host is taken is apparently important for the outcome of attempts to induce in mice experimental disseminated encephalomyelitis, for certain stocks of albino mice are susceptible and others, even though of related lines, are relatively resistant. 2. In 19% of the mice which reacted to homologous brain tissue-Freund type adjuvant mixtures, lesions characteristic of disseminated encephalomyelitis can be found in the central nervous system in the absence of any demonstrable objective symptoms of illness. 3. A diagnosis of the experimental encephalomyelitis should there-fore be based on the results of histological examination of the nervous system as well as on typical symptomatology. The question is discussed whether reactors might not have been overlooked among animals of other species hitherto employed, when the basis for the diagnosis of the encephalomyelitis was only the presence of outward signs of illness.

Certain affections of the liver that arise spontaneously in so-called normal stock albino mice.

Conclusion Certain pathological states which arise spontaneously in the livers of so-called normal stock mice, especially with increasing age, have been described. Of particular interest are the hepatic lesions of (a) infiltration and necrosis, and (b) of intranuclear inclusion bodies-both occurring in Rockefeller Institute and Swiss strains of albino mice. The relation of the two types of changes is still to be studied as well as their etiology.

Role of Heredity in Experimental Disseminated Encephalomyelitis in Mice

Conclusions An examination of 4 lines of inbred mice for susceptibility to experimental acute disseminated encephalomyelitis revealed a resistant line, BRVR, and a susceptible line, BSVS. The simplest explanation of the data here presented is that the 2 appear to differ by two resistance-conferring genetic factors either of which is adequate to bring about resistance.

Further Studies of the Agent in Intestines of Normal Mice Which Induces Encephalomyelitis

Conclusions Certain additional characteristics have been described of the active agent which is present in the intestines of normal mice and which can induce encephalomyelitis indistinguishable from that of the spontaneous Theilers disease. Among other findings, it was ascertained that, irrespective of whether mothers harbor virus (by means of artificial, cerebral inoculation or naturally in their intestinal contents), the incitant is not detectable in the intestines of their young from the fetal stage to 12 days of age, but it is demonstrable at the age of 20 days or older. Moreover, at 30 days of age, practically every mouse that has come under observation has yielded specifically active intestinal contents. By some mechanism not as yet understood, old mice harbor less of the agent than do young adults. Finally, in the latter age-group, while the mice carry regularly the active substance in their intestines, it is not at all recoverable from their brains.

Variations in Pathways by Which Equine Encephalomyelitic Viruses Invade the GNS of Mice and Guinea-pigs

Eastern equine encephalomyelitic (E.E.E.) virus, injected into the leg muscles of 15- to 21-day-old mice, invades the central nervous system (CNS) along the local peripheral nerves in only about 5% of the animals, while in most of the others it appears to be eliminated from the blood onto the olfactory mucosa, invading the CNS by the olfactory pathway, and when that pathway is blocked by preliminary chemical treatment of the nasal mucosa most, but not all, of the animals escape CNS involvement. 1 Further study by the method of partial serial sections of the entire CNS 2 revealed that when mice, given the virus intranasally, succumb in spite of the chemical treatment, the lesions are still distributed along the olfactory pathways and connections, showing that the treatment did not provide a complete barrier. When, however, mice receiving the virus intramuscularly succumb in spite of chemical blockade of the olfactory pathway, the localization of lesions indicates that the CNS was invaded by other pathways, the following types having been encountered: (a) lesions limited to the spinal cord and medulla, indicative of spread via the nerves supplying the inoculated muscle; (b) lesions involving chiefly the cochlear ganglion of one side and the inferior colliculus and medial geniculate body of the opposite side (i.e., a unilateral involvement of the auditory pathway and its central connections); and (c) lesions limited to a focus in the vicinity of the medullary nucleus of the 7th nerve. Hence, these and other pathways may occasionally be utilized by virus injected into the leg muscles (and also intraäbdominally) of normal mice as well as of those with chemical blockade of the olfactory pathway. In one normal young mouse injected intraäbdominally with E.E.E. virus both the auditory and vestibular pathways appeared to be involved. It is remarkable, however, that in these mice the localization of lesions practically always corresponded to some definite pathway, suggesting that the virus was set free in one focus from which it spread along the nervous pathways connected with it (excepting the olfactory pathway, there is as yet no evidence to indicate whether that focus is within or outside the CNS) rather than liberated indiscriminately throughout the CNS.

The Chemical Nature of Encephalitogenic Proteolipide A and B.

Conclusions Of 4 fractions prepared by chloroform-methanol extraction of mouse brain, only one, proteolipide A and B, is encephalitogenic in mice. Its desiccation which brings about a split in the bond between its protein and lipid constituents results in a loss of its encephalitogenic power and the separated protein and lipid fractions are also inactive.

Tests for Hepatic Dysfunction of Mice.

Summary Six tests for the study of hepatic dysfunction and damage were applied to Swiss mice. Insufficiently sensitive to detect hepatic lesions were the thymolturbidity test, plasma-coagulation time and vaginal-smear cytology. Cephalin-cholesterol flocculation was not applicable owing to the fact that normal mouse sera reacted positively. Blood-bilirubin determinations indicated hepatic lesions induced by carbon tetrachloride or phosphorus. The increase in bilirubin in the blood, however, even in cases of extensive damage, was not high; 0.3 mg per 100 cc of plasma in control mice as an average, as compared with 0.6 mg per 100 cc in those with carbon tetrachloride lesions. Retention of bromsulphalein was the most useful and accurate of all the tests described herein. A base line was established for control mice; i.e., less than 1 mg of dye retained per 100 cc of plasma could be regarded as normal. In mice with hepatic lesions, tested at a proper time and within the limitations mentioned, values 10 or 20 times higher than the normal were not unusual. Since retention of this dye was increased by diverse methods such as chemical poisoning, bacterial infection, starvation, and injection of autolyzed tissue, its use may be of value in the study of experimental problems connected with hepatic injury of mice.