scholarly journals FURTHER STUDIES CONCERNING THE FILTRABLE VIRUS PRESENT IN THE SUBMAXILLARY GLANDS OF GUINEA PIGS

1927 ◽  
Vol 46 (6) ◽  
pp. 935-956 ◽  
Author(s):  
Ann G. Kuttner

1. It has been shown that the guinea pig virus localizes in the submaxillary glands of young guinea pigs following subcutaneous, intraperitoneal, or intravenous injection of active material, and that the specific lesion is demonstrable in the glands in 12 to 15 days. When an active infection of the gland has been produced in this way, the guinea pigs are refractory to intracerebral inoculation of the virus. 2. No lesion develops in the submaxillary glands of young guinea pigs injected subcutaneously with guinea pig virus which has been inactivated by heat. Young guinea pigs which have received injections of heat-killed virus do not become refractory to intracerebral inoculation of the virus. 3. When young guinea pigs from which both submaxillary glands have been removed are injected subcutaneously with active virus, the virus localizes in the parotid gland, and the animals become refractory to intracerebral inoculation. 4. It has been impossible to demonstrate virucidal properties in the sera of adult guinea pigs which have become spontaneously infected with the virus, or in the sera of young guinea pigs which have been artificially rendered refractory to intracerebral inoculation. 5. It has been possible to transmit the virus from guinea pig to guinea pig continuously in series through seven animals by direct inoculation from submaxillary gland to submaxillary gland. 6. The fact that the virus regularly localizes in the submaxillary glands following subcutaneous inoculation has been utilized in passing the virus from guinea pig to guinea pig. 2 weeks after the subcutaneous inoculation of the virus into young guinea pigs, the active agent was present in the submaxillary glands. Emulsions of the submaxillary glands of these animals were then used for the subcutaneous injection of another group of young guinea pigs. In this way the virus was transmitted continuously from skin to submaxillary gland through a series of seven animals.

1934 ◽  
Vol 60 (6) ◽  
pp. 773-791 ◽  
Author(s):  
Ann G. Kuttner ◽  
Shao-Hsun Wang

1. Acidophilic intranuclear inclusion bodies occur in the salivary glands of Chinese infants dying from miscellaneous causes. The lesion is similar to that previously described in infants in Europe and America. 2. Attempts to prove that this lesion is due to an infectious agent by its production in animals have been unsuccessful. 3. Acidophilic intranuclear inclusion bodies have been found in the submaxillary glands of hamsters, white mice, and wild rats. 4. Evidence is presented to show that the lesion in hamsters, white mice, and wild rats is due to a virus, which is specific for each species, being transmissible to normal individuals of this breed, and which is very similar to the submaxillary gland virus of guinea pigs.


1922 ◽  
Vol 36 (6) ◽  
pp. 727-733 ◽  
Author(s):  
William A. Hagan

1. White mice are highly susceptible to infection by inoculation with Bacillus abortus. The susceptibility appears to be as great as that of the guinea pig, and this animal probably can be substituted satisfactorily for guinea pigs in diagnostic work. 2. Both mice and rats are very refractory to feeding infection with Bacillus aborlus. The failure to infect mice in this way was complete, but the feeding of large amounts of culture gave infection in rats. Subcutaneous inoculation resulted in infection of all the animals. The difficulty of infecting rats and mice with Bacillus abortus by feeding makes it very doubtful whether these animals can have any rôle in the propagation and spread of infectious abortion in cattle.


1919 ◽  
Vol 29 (6) ◽  
pp. 585-596 ◽  
Author(s):  
Hideyo Noguchi

Studies are reported on the type of disease induced in guinea pigs, dogs, and monkeys by inoculating them (1) with the blood or organ emulsions of guinea pigs or other susceptible animals experimentally infected with Leptospira icteroides, and (2) with a pure culture of the organism. Particular attention has been given in these experiments to the clinical features of the experimental infection in the various animals and to the pathological changes resulting from the infection. The symptoms and pathological lesions induced in guinea pigs are much more pronounced than those observed in dogs or marmosets. The period of incubation is nearly the same in all three species, 72 to 96 hours with intraperitoneal or subcutaneous inoculation, and a day or more longer when the infection is induced percutaneously or per os. The febrile reaction in the guinea pig and marmoset is about the same; in the dog there is less fever. The amount of albumin, casts, and bile pigments in the urine is more abundant in the guinea pig and marmoset than in the dog, and these animals also appear on the whole to become more intensely icteric. The black or bilious vomit, however, though occurring frequently in dogs during life, is observed in the guinea pig and marmoset at autopsy. The hemorrhagic diathesis is most pronounced in guinea pigs, less so in marmosets, and least in dogs. In dogs) for example, subcutaneous hemorrhages almost never occur, and the lungs usually show only a few minute ecchymoses. The pleurse, pericardium, and other serous surfaces of the thorax and abdomen remain free from ecchymoses, which, however, with hyperemia, are very marked along the gastrointestinal tract. The symptoms and lesions observed in animals experimentally infected with Leptospira icteroides closely parallel those of human yellow fever. The pathological changes occurring in human cases of yellow fever are similar to those induced by inoculation in guinea pigs and marmosets and in respect to their intensity stand intermediate between those arising in the two animals mentioned.


1933 ◽  
Vol 57 (6) ◽  
pp. 925-931 ◽  
Author(s):  
Richard E. Shope

Pseudorabies virus, Iowa strain ("mad itch"), after passage through guinea pig brain, fails to produce infection in guinea pigs when injected subcutaneously unless enormous doses are employed. Such virus is still pathogenic for rabbits when given subcutaneously and for rabbits and guinea pigs intracerebrally. Comparison of the amounts of virus present in the brains of rabbits and guinea pigs following fatal cerebral infection shows that the latter contain, per gram, only approximately one-tenth the amount of virus in the former. Comparing the resistance of the two species to subcutaneously administered pseudorabies virus it has been found that rabbits are approximately 100 times more susceptible than guinea pigs. Over and above the working of these two factors, guinea pig passage appears to achieve some actual attenuation of virus when tested by subcutaneous inoculation into guinea pigs.


1933 ◽  
Vol 58 (6) ◽  
pp. 663-681 ◽  
Author(s):  
Erich Traub

Pseudorabies virus has been cultivated in series in rabbit testicle, guinea pig testicle, and chick embryo media, and its growth requirements have been studied. Intranuclear inclusions, similar to those produced by pseudorabies virus in vivo, have been found in rabbit testicle cultures. The virus has not changed its pathogenic properties for rabbits, guinea pigs, or mice during the course of cultivation.


1927 ◽  
Vol 45 (4) ◽  
pp. 673-683 ◽  
Author(s):  
Peter K. Olitsky ◽  
Louis Boëez

A strain of foot-and-mouth disease virus was recovered from a cow at the height of the disease, and was propagated through at least 261 passages in the guinea pig. Considerably over 2000 animals proved susceptible to the virus, and the virus could be transferred at will back to cattle and hogs, and then again returned to guinea pigs. No natural immunity was discovered in guinea pigs. Secondary lesions were easily and regularly induced, thus making this strain particularly favorable to experimental purposes. In general, the guinea pig may therefore be regarded as the animal of choice for laboratory studies. The guinea pig could be infected by different methods of injection in different sites, but constant and regular production of primary and secondary lesions—or generalization of the disease—followed intradermal "tunneling" in the manner described, combined with subcutaneous inoculation of the posterior hairless pads of full grown animals. As we have indicated, the virus was peculiarly epitheliotropic, which in turn gives support to the opinion that its portal of entry may be limited. The active agent could purify itself of chance concomitant bacteria in the first passages, in a susceptible animal—a character possessed by filter-passing viruses in general. The virus was active in dilutions of 1:10,000,000. This shows not only the minuteness of the active agent, but also the necessity for a change of technique from that employed with larger sized infectious agents. Apart from this, the dilution factor is important in interpreting mere preservation of the virus rather than multiplication, when only early successive subplants in culture experiments are positive. Furthermore, some samples of virus were not so active—a factor of twenty-five existed between the weakest and strongest samples among fifteen titrated. This indicates that comparative tests, as, for example, of survival in different media, should be made with the same specimen. In any case, the rate and energy of action of the virus were proportional to its concentration, thus differing from the behavior of certain enzymes. The incitant is not sedimented by centrifugation. Non-centrifugability, a property of some other filter-passing, infectious agents, is not an indication of the fluid character of the virus, as we have already explained. In view of the evidence presented and other tests to be reported later, failure of deposition is related to the minute size of the incitant. The method of centrifugation has also failed to remove "virucidal bodies" in the meaning of Frosch and Dahmen.


1954 ◽  
Vol 100 (5) ◽  
pp. 425-435 ◽  
Author(s):  
Alvin F. Coburn ◽  
Claire E. Graham ◽  
Joan Haninger

Whole egg yolk incorporated as a supplement in the diet of baby guinea pigs afforded protection against anaphylactic arthritis as determined: (a) by measurement of joint swelling; (b) by the rise in serum level of some substance which reacts with diphenylamine; (c) by histologic examination. The active material in egg yolk was shown to be in the alcohol-soluble fraction. Attempts to identify the active material with any known lipid have to date been unsuccessful. In the screening of lipid substances for protection against anaphylactic arthritis, it is shown that the weanling guinea pig is suitable, that a 3 week period is adequate, and that the test substance can be administered satisfactorily in the diet.


1935 ◽  
Vol 62 (6) ◽  
pp. 805-822 ◽  
Author(s):  
Ann G. Kuttner ◽  
T'sun T'ung

1. It has not been possible to increase the virulence of the submaxillary gland viruses of guinea pigs and rats, either by reducing the resistance of the animals by exposure to X-ray, or by the addition of testicular extract (Duran-Reynals factor). 2. In guinea pigs and wild rats with spontaneously infected submaxillary glands, the kidney has been found to contain the virus in the absence of demonstrable pathological changes. 3. Direct injection of these viruses into the kidney produces only mild, circumscribed lesions. 4. The viruses, following subcutaneous injection into white rats and guinea pigs, are widely distributed 2 weeks after injection. They are present in the submaxillary glands, cervical lymph nodes, kidney, and lung. They were not demonstrable at this time in the blood, liver, or spleen. 5. By the intratracheal injection of large doses of virus in guinea pigs and rats, an interstitial bronchopneumonia with thickening of the alveolar and bronchial walls and the presence of acidophilic inclusion bodies, can be produced. 6. No evidence was obtained to indicate that the multiplication of bacteria in the lung is greatly enhanced by the injection of these viruses.


1932 ◽  
Vol 55 (3) ◽  
pp. 405-415 ◽  
Author(s):  
N. Paul Hudson ◽  
Floyd S. Markham

The submaxillary gland virus of guinea pigs was serially transmitted from brain to brain in young guinea pigs. The source of virus was the submaxillary glands of six groups of stock animals. Brain to brain transfer was effected in two series, in one to the second generation and in the other to the third. The transmission was evidenced by the presence of nervous symptoms and death and by a typical microscopic pathology of the brain. Only certain attempts were successful, ten of twenty-three brain to brain injections being fatal with the specific histopathology present in five. A few observations suggest that the virus may be present spontaneously in the gland and experimentally in the brain without cellular changes being demonstrable, or before they are evident. While we were able to transmit the virus from brain to brain with fatal results by single injections of small doses, this was not readily accomplished and the transmission failed after two or three passages. We were unable to show any perceptible increase in virulence or adaptation of the virus to the brain tissue of the natural host. The histopathology was that of a meningoencephalitis. The inflammatory reaction irregularly involved the meninges, the underlying brain substance, and the perivascular tissue of the meninges and upper cortical layer. These structures were infiltrated with mononuclear cells, many of which contained a typical acidophilic inclusion. Congestion of cerebral capillaries uniformly occurred and various degrees of recent hemorrhage were frequently found. Necrosis was noted only when associated with an occasional area of extensive hemorrhage. Similar changes were observed in sections of the spinal cord. When sufficient time (15 days or more) elapsed between cerebral inoculation and death, typical cellular inclusions were seen in the salivary glands, whereas none was found in animals that died earlier (7 to 9 days). Under the first mentioned conditions, inclusions were demonstrated in the parotid and mucous portion of the submaxillary glands, although in spontaneously infected animals, we failed to find the mucous portion involved and other workers report that the parotid is spared. About one-third of the stock guinea pigs examined showed cellular inclusions in both the nucleus and cytoplasm of epithelial duct cells of the serous part of the submaxillary gland. From an analysis of the results of brain to brain inoculations, it was evident that spontaneous infection and resistance to cerebral inoculation increased with age. The 3rd week of life is the period of choice for such experimentation.


1926 ◽  
Vol 44 (6) ◽  
pp. 855-873 ◽  
Author(s):  
Rufus Cole ◽  
Ann G. Kuttner

In the lesions of herpes simplex and similar conditions due to filterable viruses, cells are present which show characteristic alterations, particularly in the nucleus. The nucleus of these cells contains a mass which stains with acid dyes. Surrounding this mass is a clear space or halo, within which there are large granules staining with basic stains. These cells are little if at all enlarged. In a few human cases, especially in infants, enlarged cells have been found which contain nuclei showing changes similar to those seen in the abnormal cells of herpes simplex. In the ducts of the submaxillary glands of guinea pigs, Jackson observed structures which she considered to be protozoan parasites. Our own studies indicate, however, that these structures are greatly swollen epithelial cells with nuclei having the same characters as the nuclei of the atypical cells in the lesions of herpes simplex. These cells are usually surrounded by a mononuclear cellular reaction. They were found in 84 per cent of the full grown guinea pigs examined but they were present in only three of forty-three young guinea pigs less than 1 month old. The resemblance of these cells, except as regards size, to the atypical cells present in lesions due to filterable viruses suggested that they also may be the result of an infection with a similar agent. That they are usually not present in guinea pigs less than 1 month old indicates that natural infection usually occurs after this period. Experiments were therefore undertaken to determine whether or not an infective agent is concerned in this condition and if so to learn something of its nature. When an emulsion of the submaxillary glands of full grown guinea pigs is injected into the brains of young guinea pigs the animals have fever and exhibit symptoms of cerebral irritation. They usually die in 5 to 7 days and in sections of the brain a diffuse subacute meningitis is found. In the exudate there are large numbers of cells having all the characteristics of the abnormal cells of herpes simplex. Similar cells are present in the lesions resulting from the injection of the same emulsion into the testicle, lung, tongue, and submaxillary glands of young guinea pigs. In none of these lesions, however, are the cells greatly enlarged as they are in the lesions in old guinea pigs. These results support the view that the lesion in the submaxillary gland of old guinea pigs is due to an infective agent. Attempts were therefore made to transmit this agent through a series of young guinea pigs. When the injections were all made into the same organ all the experiments but one gave negative results, but when the site of injection was changed at each transfer it was possible in a number of instances to reproduce the lesions through two animals in series and in one experiment through three animals in series. By modifying the technique, efforts were made to transmit the infection indefinitely but these attempts were unsuccessful. No explanation can be offered for this failure. Studies made to determine some of the properties of the infective agent have shown that it is destroyed by heating at 54° for 1 hour, and that it is not injured by preservation in 50 per cent glycerol for as long as 11 days. After the material had remained in 50 per cent glycerol for 28 days, however, it was found to be no longer infective. The infective agent was not held back by a Berkefeld N filter which was impermeable to bacteria. It seems probable therefore that the infective agent belongs in the group of filterable viruses, though further work will be necessary to learn more of its exact nature. These observations present additional evidence that the presence of cells with nuclear inclusions in any lesion indicates that the injury is probably due to an infective agent belonging in the group of filterable viruses.


Sign in / Sign up

Export Citation Format

Share Document