Uninoculated Mice Research Articles

POSSIBLE TRANSMISSIBILITY OF HUMAN MYELOMATOSIS IN IMMUNOLOGICALLY DEFICIENT MICE

Bone-marrow cells from a patient with untreated myelomatosis have been inoculated intravenously into adolescent mice thymectomised before total-body irradiation. The inoculation of intact human cells and subsequent mouse passages of pooled intact cells, broken cells, and of non-irradiated broken-cell filtrates all yielded histological and serological features of malignancy largely indistinguishable from those seen in the human donor. Conversely, these changes were not present in uninoculated but comparable mice similarly prepared or in mice receiving broken-cell filtrate exposed to cobalt irradiation. These findings provide evidence of a filterable and viable transmissible agent for myelomatosis.

An Attempt to Determine Whether Maternal Transmission of Scrapie Occurs in Mice

SUMMARY Female mice inoculated with scrapie agent were housed with uninoculated male mice. A proportion of the litters that were born were observed for evidence of the disease but no cases of scrapie were seen. When the progeny were challenged with scrapie they reacted at the same time as control mice. There was no evidence for maternal transmission of scrapie, or that resistance was conferred to mice born of scrapie-affected dams.

The Occurrence of Nerve Fibre Degeneration in Brains of Mice Inoculated with Scrapie

SUMMARY Mice of 3 inbred strains were inoculated intracerebrally with a standard scrapie agent. At weekly intervals, from about halfway through the incubation period, groups of each strain were killed and their brains examined histologically. A silver impregnation method teas used to demonstrate degenerating nerve fibres selectively. Un-inoculated mice of the same 3 strains were treated similarly. A number of mice of other strains inoculated both intracerebrally and intraperitonealy were similarly examined. During the development of the disease and at the clinical stage, when nerve fibre degeneration became apparent, this was much more severe in the scrapie inoculated mice than in the controls.

The absence of glucose in ehrlich ascites tumor cells and fluid

Microdetermination of sugar in Ehrlich ascites tumor cells and fluid was carried out by the fluorimetric method with 5-hydroxy-1-tetralone. In the ascitic fluid from the 4th to 12th day after inoculation, sugar concentration was practically constant regardless of the day after inoculation, and no glucose was found. However, from the 14th to 16th days after inoculation this constancy of sugar concentration was not observable in teh ascitic fluid and a small amount of glucose was detectable in the cell-free fluid. By paper chromatographic analysis the main sugar component in cell-free ascitic fluid was suggested to be a neutral and reducing oligosaccharide, and sugar in normal peritoneal fluid from uninoculated mice was found to be mostly glucose.

Duration of Immunity to Tuberculosis in Mice Vaccinated Intravenously with Oil-Treated Cell Walls of Mycobacterium Bovis Strain Bcg

Summary Resistance of mice to aerosol infection by Mycobacterium tuberculosis H37Rv engendered by intravenous (i.v.) administration of BCG cell walls treated with Drakeol 6-VR or viable BCG has been studied by determining the number of virulent organisms and the presence of tuberculous lesions in 1) lungs of vaccinated and uninoculated control mice 1 month after challenge infection at various intervals up to 28 weeks after immunization and in 2) lungs of mice challenged 1 month after immunization and sacrificed at various intervals up to 231 days after challenge. Mice inoculated with the cell wall vaccine and challenged at various intervals consistently had fewer and smaller tuberculous lung lesions than did the BCG-vaccinated and control mice at all intervals tested, fewer organisms in the lungs than did the control mice at all intervals tested, and fewer organisms in the lungs than did the BCG-vaccinated mice at all times except at the longer intervals (21 to 28 weeks) when the numbers for both were about equal. Mice inoculated with the cell wall vaccine, challenged 1 month later and sacrificed at various intervals after challenge, had fewer and smaller lung lesions than did the BCG-vaccinated and control mice at all intervals up to 231 days after challenge, fewer virulent organisms in the lungs than did the control mice at all times, and fewer organisms in the lungs than did the BCG-vaccinated mice at all times except at the later intervals (180 to 231 days) when the numbers were nearly the same. Lung weights of mice inoculated with the cell wall vaccine were greater than those of the BCG-vaccinated and control mice at the time of challenge; resistance of the mice to challenge was correlated with lung weight, but it is not known whether this lung enlargement was directly related to immunity. These results indicate that the BCG cell wall vaccine, when administered i.v., confers to mice, for an extended period of time, resistance to aerosol infection superior or equal to that afforded by viable BCG.

Spread of scrapie from inoculated to uninoculated mice.

SummaryScrapie occured in 7 of 200 uninoculated control mice housed in the same room with, but caged separately from, successive groups of scrapie inoculated mice. Clinical evidence of the disease appeared in controls as early as 16 months and as late as 22 months after initial exposure to scrapie inoculated mice.

Viral leukemias in mice.

with gradual short­ ening of latency and increased incidence of leukemia (12). This passage G virus, when inoculated into newborn Ak mice, causes gener aliz ed leu­ kemia within two to three months in all of the animals; uninoculated Ak mice develop leukemia in a much lower percentage at nine months of age and later (13). Independently, Gross was first to demonstrate the viral etiology of mouse leukemia by using a different approach. He showed, in 1950 and 1951, that a leukemogenic agent can be transferred from high-leukemia Ak strain mice to low-leukemia C3H strain mice (especially to Bittner's sub­ line, less successfully to Andervont's, or NIH subl ines), if newborn C3H strain mice are inoculated with cell-free extracts or filtrates of Ak strain leukemic organs (14 to 17). The leukemia induced in C3H strain mice was of the generalized lymphatic type. It developed in 28 to 66 per cent 1 The survey of the literature pertaining to this review was concluded in January, 1962. • The author's appreciation is expressed to Dr. C. A. Evans for suggesting that this review be written, and for his comments on it; to Dr. V. Groupe for reading the manuscript and kindly commenting on it; to Drs. Charlotte Friend, J. B. Moloney, F. J. Rauscher, B. P. Maduros, and R. Pienta for discussions on this subject; and to those who kindly submitted unpublished information. The author is especialIy obliged to Dr. L. Dmochowski for mindful and very valuable corrections made throughout the entire manuscript.

Reduced activity of histaminase in rats sensitized by Bordetella pertussis.

SINCE Parfentjev and Goodline1 published their work on histamine hypersensitivity induced by inoculation of Bordetella pertussis (reviewed by Kind2) a number of papers on the subject have appeared; but little has been reported of the related biochemical changes in connexion with susceptibility to histamine. Inactivation of histamine by lung tissues from mice inoculated with B. pertussis was reported by Kind et al. 3 to decrease as compared with tissues from uninoculated mice. But this interesting result was not repeated by the same authors. More recently, Fishel4 has examined changes in amino-acids, histamine and glutathione contents in various organs from inoculated mice, revealing no specific changes referable to histamine hypersensitivity. The present communication deals with the results concerning reduced activities of histaminase in tissue of rats inoculated with B. pertussis.

Antagonism of cortisone to body temperature reducing effect of histamine.

Pertussis-inoculated mice are more sensitive to body temperature lowering effect of histamine than uninoculated animals. Cortisone reduces the temperature drop in both pertussis-inoculated and uninoculated mice.

Adrenal function tests in mice sensitized to histamine with Hemophilus pertussis vaccine.

An increase in liver glycogen occurred in both fasting uninoculated and fasting pertussis-inoculated mice when exposed to 1/2 atmosphere pressure for 24 hours. Exposure at 3/8 atmosphere for 24 hours killed 17 of 18 pertussis-inoculated mice and only 3 of 18 uninoculated animals.

The intracellular localization of poliomyelitis virus.

A study was made of the intracellular localization of Type 2 poliomyelitis virus, using the technique of Mirsky and Pollister (23) for cellular fractionation. After isotonic saline homogenization of central nervous system tissue from infected mice, and subsequent centrifugation of the suspension, the virus present in the supernatant fluid was held to be of cytoplasmic origin. Upon serial washings of the sediment with physiological saline, the resulting supernates contained progressively less virus until by the seventh washing, virtually none was present. At this point extraction of the washed sediment with molar NaCl, which lyses the nuclei, yielded substantial amounts of virus, and this was assumed to be from nuclear sources. The possibility has not been excluded however that the "nuclear" sediment was contaminated by cytoplasmic particles too large to remain in the supernate. Experiments on the increase of virus during the incubation and acute stages of infection have revealed that it was first detectable in the "cytoplasmic" fraction and subsequently in the "nuclear" fraction. Virus in the "nuclear" fraction from paralyzed mice sometimes reached titers almost as high as those found in the "cytoplasm." Adsorption experiments indicated that the "nuclear" fraction of CNS tissue from normal, uninoculated mice did not adsorb added Type 2 poliomyelitis virus, nor did such fractions adsorb virus procured from the "cytoplasm" or "nuclei" of infected cells. Although individual mice varied in their response after virus injection, the "cytoplasmic" fraction of paralytic mice was found to contain virus regularly, whereas little more than half of the non-paralytic mice yielded it. When virus was present in the "cytoplasm," it could be found in the "nuclear" fraction of paralytic mice with much greater regularity than in that of non-paralytic mice. A comparison between the lines of the MEF1 strain of poliomyelitis virus, "adapted" and "non-adapted" to newborn mice, and the Lansing strain, revealed no differences in their intracellular increase. In both infant and adult mice, the chief difference in the findings with non-paralyzed and paralyzed mice lay in the greater concentration of virus in the "nuclear" fractions of the latter group.

Inhibition of histamine death in pertussis-inoculated mice by cortisone and neoantergan

Cortisone inhibited the lethal effects of both histamine and H. pertussis vaccine in pertussis-inoculated mice. Cortisone also protected uninoculated mice from toxic death due to H. pertussis vaccine. The antihistamine, Neoantergan, protected pertussis-sensitized mice from the lethal effects of histamine but not from fatal amounts of H. pertussis vaccine. The advantages of using pertussis-inoculated, histamine-sensitive mice rather than guinea pigs in the screening of compounds which might be active against histamine are discussed.

A spontaneous epizootic of mouse encephalomyelitis.

SummaryA spontaneous epizootic of encephalomyelitis which killed 62%percnt; of 240 uninoculated mice is described. A virus was isolated which resembles GD VII virus in its properties, and which is ...

Oral administration of Coxsackie viruses to newborn and adult mice.

Summary(1) Newborn mice may be infected by oral administration of at least 5 different strains, representing 4 immunologically distinct Coxsackie, or C, viruses. Adult mice were resistant. (2) Newborn mice surviving oral administration may produce neutralizing antibodies. (3) Adult female mice fed C virus did not transmit neutralizing antibodies to their offspring, in contrast to females inoculated parenterally. (4) In a comparison of routes of inoculation of newborn mice it was found that higher titers may be reached by subcutaneous than by oral administration. The subcutaneous route proved to be about 10,000 times more sensitive than the oral route. (5) Direct contact between inoculated and uninoculated mice did not result in the transmission of infection.

THE EFFECT OF DIET ON THE SUSCEPTIBILITY OF THE MOUSE TO PNEUMONIA VIRUS OF MICE (PVM)

Young mice fed diets deficient in pyridoxine for 8 days or longer before the inoculation of PVM, as well as after inoculation, were more susceptible to infection than control mice fed complete diets. Young mice fed a pyridoxine-deficient diet gained weight as well as controls fed a complete diet for 5 weeks, but they lost weight in the 6th week. The ratio of thymus or spleen weight to body weight was less in mice fed a pyridoxine-deficient diet for 6 weeks than in controls fed a complete diet. Histologically the thymuses and spleens showed hypoplasia. No measurable difference in antibodies against PVM was found in the sera of uninoculated mice fed complete or pyridoxine-deficient diets for 6 weeks.

A FILTERABLE VIRUS CAUSING ENTERITIS AND PNEUMONIA IN CALVES

An infectious disease of calves has been described which is characterized by fever, diarrhea, and pneumonia, followed soon by recovery. On autopsy of animals killed at the height of the disease, there is found a catarrhal enteritis and a bronchopneumonia that is usually confined to the anterior lobes of the lungs. From this disease an agent has been secured by the serial inoculation of lung extracts that produces a pneumonia in white mice. Attempts to demonstrate by the same means a similar agent in uninoculated mice from the same stock have yielded negative results. Suspensions of the lungs of the mice with pneumonia, when inoculated intranasally or intratracheally into calves, cause a disease like the natural infection, characterized by fever, diarrhea, and pneumonia. In two experiments pen contact of normal calves with calves inoculated with the passed material resulted in the typical disease. Early in its course the causative agent is found only in the lungs and intestines, but at its height is generally distributed throughout the body. Calves that have recovered from the induced disease are resistant to subsequent infection and their blood serum will neutralize the causative agent as not previously. Sera from calves that have recovered from the natural disease also neutralize the agent. Cultures from the infected lungs of calves and mice as a rule show no growth, and material that has been passed through Berkefeld N filters produces the characteristic disease. It is therefore concluded that this disease of calves is caused by a filterable virus.

A Pneumonia Virus of Swiss Mice

A virus capable of inducing fatal pneumonia in Swiss mice has been isolated from normal mouse lungs, and its immunological characteristics are now being studied in detail.Twenty-one groups of normal Swiss mice were inoculated intra-nasally under ether anesthesia with 0.05 cc of lung-suspensions from uninoculated mice. Serial mouse-passage was carried on with each group, using 10% to 30% lung-suspensions. Passages were made at an average interval of 7 days; usually 6 mice were used in each group. The mice were obtained from 6 different breeders. Initially, passages were made without regard to the breeder from whom the mice had been obtained. Lately, however, passages have been made in mice from each individual breeder in order to determine the source of the virus. Definite areas of pulmonary consolidation were present in 43% of the groups in the third serial passage, and in 52% of the groups at the sixth passage. Death occurred as early as the fourth passage, and by the sixth passage deaths were recorded i...