Allergy and immunity in tuberculosis. I. Immunization and reinfection of guinea pigs with homologous variants of the human tubercle bacillus H37

1943 ◽  
Vol 14 (5) ◽  
pp. 434
1929 ◽  
Vol 50 (3) ◽  
pp. 365-370 ◽  
Author(s):  
Richard E. Shope ◽  
Paul A. Lewis

The experimental data collected during this study of a transmissible type of paralysis developing in tuberculous guinea pigs indicate the condition to be a true tuberculous meningitis. We have been able to rule out the possibility that it is due to a non-tuberculous infection of the central nervous system caused by Roemer's virus, or by an atypical herpes virus, or by some bacterium other than the tubercle bacillus. Roemer's virus and herpes could be eliminated from consideration when Berkefeld N filtrates of infectious brain emulsions proved incapable of reproducing the disease. Furthermore, rabbits could be infected as they cannot with Roemer's virus, and the disease elicited in rabbits bears no semblance to herpes encephalitis. No organism other than the tubercle bacillus could be obtained on culturing brain or brain emulsions from experimental cases, and no others were seen in examining fresh smear preparations from the central nervous system. In a modified Noguchi medium a tubercle bacillus possessing atypical staining properties was obtained. This organism was capable of producing the typical paralytic disease when injected intracerebrally into guinea pigs, and also generalized tuberculosis in animals inoculated subcutaneously with it. Typical tuberde bacilli were readily demonstrable in sections of the meninges from animals with the disease, and culture of pieces of brain on Dorset's egg medium usually yielded a growth of tubercle bacilli. Only in the first of the experimental passages, on the other hand, was it possible to demonstrate acid-fast organisms in fresh smear preparations from the central nervous system. This fact and the attributes of the atypically staining organisms encountered in the cultures in Noguchi media will be considered more fully in a subsequent publication. In view of the much discussed question of the filtrability of the tubercle bacillus our observations concerning the failure of this organism to pass a Berkefeld N filter are of interest. No animal in our series inoculated intracerebrally with brain emulsion from either a "spontaneous" or experimental case of tuberculous meningitis failed to develop meningitis, and that rather acutely, while no animal in our series injected with a Berkefeld filtrate of brain emulsion has developed tuberculous meningitis or any other form of tuberculosis. In connection with this observation it must be recalled that the organism was atypical in respect to its staining qualities at least.


1940 ◽  
Vol 40 (3) ◽  
pp. 365-376 ◽  
Author(s):  
A. Stanley Griffith

1. The types of tubercle bacilli have been determined in the sputum of 515 cases of pulmonary tuberculosis occurring in the middle and south of Scotland.2. Of the 515 cases 484 were human (476 eugonic and eight dysgonic) and thirty-one were bovine infections.3. With the exception of the strains from one case (case 28) all the bovine strains, seventy in number, were typical culturally and fully virulent for rabbits.4. The attenuated strains, two in number, from case 28 were slightly less virulent than typical bovine strains for rabbits and (one strain) for guinea-pigs.5. The percentage of bovine infections found in this series, including the Cumberland case, during the years 1931–9 was 6·0, but excluding that case it was 5·8.6. The percentage of bovine infections found by Munro during about the same period and covering the same regions was 5·0%.7. In Munro's series strains of bovine tubercle bacilli were obtained from fifty-eight out of 1165 persons (5·0%). Five of his cases yielded attenuated bovine strains and in one of these the pulmonary tuberculosis was preceded by tuberculosis of the thoracic spine.8. In my series the attenuated tubercle bacilli came from a case (case 28) of pulmonary tuberculosis which was preceded nearly 20 years previously by tuberculosis of the lower dorsal spine.Dr Munro and others have made post-mortem examinations on cases of phthisis pulmonalis due to bovine bacilli, but I wish to defer reference to these until we can review them altogether.In this series there are seven instances of cervical gland enlargement and one instance (case 28) of spinal tuberculosis occurring previous to the development of phthisis pulmonalis. These, I think, are examples of alimentary infection with the bovine tubercle bacillus. Thus, with the three autopsies previously mentioned, there are eleven cases, or about one-third, which are almost certainly alimentary in origin. As for the rest of the cases, 20 in number, no glandular enlargements in neck or abdomen were detected but the majority, if not all, were probably alimentary in origin, since all the persons drank a lot of raw milk and only five came into direct contact with cattle in their employment.


1924 ◽  
Vol 23 (3) ◽  
pp. 260-267 ◽  
Author(s):  
C. C. Twort

IN 1913, Fraenkel and Much1 inoculated monkeys, guinea-pigs, rabbits and dogs intraperitoneally with large quantities of material obtained from two cases of Lymphadenoma, no accompanying tubercular disease being demonstrable. The material was broken down with antiformin, and as a result of the injections, the guinea-pigs died within three months. The authors state that besides finding extensive tubercular disease, there were hard, white nodules, the size of a cherry stone, on the serous coverings of the stomach and mesentery. Also, in addition to genuine tubercular disease of the lymphatic glands, they found giant cells, not of Langhans' type, as well as a stroma rich in fibriles, similar to what is found in Lymphadenoma. The nodules on the serous surfaces showed a picture corresponding to the terminal fibrous stage of a lymphadenomatous focus, with a scarcity of cellular elements.


1949 ◽  
Vol 90 (1) ◽  
pp. 53-72 ◽  
Author(s):  
Sidney Raffel ◽  
Louis E. Arnaud ◽  
C. Dean Dukes ◽  
Jwo S. Huang

Guinea pigs sensitized with egg albumin along with the purified wax fraction of the human tubercle bacillus respond with delayed hypersensitive reactivity to the protein antigen. Previous publications have reported a similar activity of the wax with respect to tuberculoprotein and picryl chloride. The effect is not referable to an ordinary adjuvant activity of the bacillary wax, since antibody titers are not increased in animals which receive it, and since a known adjuvant, water-in-oil emulsion, has no effect with respect to the induction of delayed hypersensitivity. This report further extends the rôle of the tubercle bacillary wax in the induction of delayed hypersensitive states.


1930 ◽  
Vol 2 (6) ◽  
pp. 406-408 ◽  
Author(s):  
Chas. A. Mitchell ◽  
R. C. Duthie

Tubercle bacillus, isolated from an avian source, the common crow, remained alive in the udder tissue of a cow 210 days after intravenous inoculation without producing demonstrable macroscopic lesion; reinoculated from the udder tissues into laboratory animals it proved virulent, and caused progressive lesions in chickens and rabbits but not in guinea pigs.


1944 ◽  
Vol 22e (5) ◽  
pp. 95-121 ◽  
Author(s):  
K. I. Melville ◽  
R. L. Stehle

Seventy-nine compounds comprising 22 p-aminobenzene derivatives, 10 o-aminobenzene derivatives, 11 m-aminobenzene derivatives, 8 p-N-ethyl-aminobenzene derivatives, 10 isomeric hydroxychloroanilines, 3 diaminodiphenylsulphones and 15 miscellaneous agents, have been compared for their effects upon the course of experimental tuberculosis in guinea pigs inoculated intraperitoneally with virulent human tubercle bacillus (Strain H 37 R. V.). Sixty-five of these compounds gave entirely negative results. On the other hand, 14 of the agents tested, namely, p-aminophenol, p-ethylaniline, p-chloroaniline, p-aminophenyl hexyl ether, ethyl-p-aminobenzoate, 2,4-dichloroaniline, p-N-ethylaminophenol, 3-chloro-4-hydroxyaniline, 2-chloro-4-hydroxyaniline, 2-chloro-5-hydroxyaniline, 2-hydroxy-3-chloroaniline, promin, rodilone, and sulphathiazole led, in a number of different experiments, to varying degrees of prolongation of the survival time of some of the animals treated with them, in comparison with both untreated controls and animals treated with other agents. The average survival times of all the animals treated with these agents were also prolonged in several different series of experiments in which each of these agents was tested. None of the latter agents led to a curative effect and all animals both treated and untreated, however long they survived, showed at autopsy gross evidence of tuberculosis involving spleen, liver, lungs, and glands. Finally, it must be emphasized that none of these compounds offer any promise as a cure for tuberculosis, but the results described would suggest that further investigation of chemical agents related to these substances might be worthwhile.


1921 ◽  
Vol 33 (6) ◽  
pp. 751-762 ◽  
Author(s):  
Frank A. McJunkin

1. When a guinea pig with well developed peritoneal tuberculosis is injected intraperitoneally with about 20 cc. of a heavy suspension of a virulent tubercle bacillus (Culture H37) death occurs within 24 hours or the animal becomes extremely toxic. Such a peritoneal tuberculosis develops in about 1 month after 1 cc. of. a very heavy suspension of Culture H37 has been introduced into the abdominal cavity. If the viscid fluid which is contained within the peritoneal cavity is mixed with saline solution and passed through a Berkefeld filter a bacillus-free filtrate is obtained which induces in normal guinea pigs a certain degree of cutaneous hypersensitiveness to tuberculin. 2. The abdominal organs and the parietal peritoneum, to which masses of leucocytes and tubercle bacilli are adherent, when crushed and extracted with saline solution yield a filtrate which likewise induces a cutaneous hypersensitiveness. 3. The cutaneous hypersensitiveness does not appear before the 7th or 8th day after the filtrate injection and is therefore considered to be the result of an active sensitization of the animal.


1926 ◽  
Vol 44 (5) ◽  
pp. 623-624 ◽  
Author(s):  
Richard E. Shope

Three suspensions of tubercle bacilli in physiological salt solution were still virulent for guinea pigs after 310, 325, and 330 days at refrigerator temperature. One of these cultures on which recent tests had been made had lost very little, if any, of its virulence for guinea pigs in 325 days.


1931 ◽  
Vol 54 (3) ◽  
pp. 387-397 ◽  
Author(s):  
Joseph D. Aronson

Tuberculin from the human and from the bovine type of tubercle bacilli inhibits the growth of cells from explants of bone marrow, spleen and testes of tuberculous guinea pigs, and is toxic for these cells, but has no effect on explants of the same tissues from non-tuberculous animals. "Tuberculin" from other acid-fast bacteria has no inhibitory or toxic action on explants of tissues from either tuberculous or non-tuberculous guinea pigs. Tuberculins from the avian, bovine and human types of tubercle bacillus as well as "tuberculin" prepared from the Duval and from the Kedrowsky strains of M. leprae inhibit the growth of the cells of explants of the spleen and bone marrow of tuberculous fowls and are toxic for these cells, but have no effect on the explants from tissues of non-tuberculous chickens. "Tuberculins" from other acid-fast bacteria have no effect on the growth of explants of tissues from tuberculous or from non-tuberculous fowls. Tissue culture methods indicate that the sensitivity of tuberculous tissues to tuberculin is inherent in the cell, and that it cannot be passively transferred.


1914 ◽  
Vol 14 (1) ◽  
pp. 52-71 ◽  
Author(s):  
Leonard S. Dudgeon

Experience gained from a previous enquiry on this subject in human tuberculosis led to the belief that much information might be derived from an investigation of the complement fixation reaction in animals experimentally infected with tubercle bacilli. Accurate dosage can be measured and the true path of infection is definitely known. Various enquiries were suggested and investigated by the detailed examination of rabbits and guinea-pigs; the latter class of rodents were used in batches of six to twelve in number, as otherwise the individual differences between animals in the same group of experiments are entirely overlooked. My cultures of the human tubercle bacillus were obtained by inoculating guinea-pigs with the sputum from typical cases of pulmonary tuberculosis at the Brompton Hospital Sanatorium at Frimley. Pure cultures of the bacillus were obtained from the infected guinea-pigs and cultivated on Dorset's egg medium, so that within a period varying from 14 to 21 days an abundant growth was obtained. The culture of the bovine bacillus was supplied to me by Professor Delépine who obtained it directly from the tissues of an infected cow, and subcultures were kept going on Dorset's egg medium. In every experiment without exception the animals were infected with definitely known quantities of the human or bovine bacillus. These were obtained by carefully scraping the growth off the surface of the egg medium and weighing it on sterile platinum foil, while in some cases (for comparison) a portion of the growth was dried in a desiccator before it was weighed. The untreated or dried bacilli were then shaken in a known quantity of sterile saline, so that a perfect emulsion free from clumps was obtained. The bacilli were kept in the dark in brown stoppered bottles and were always employed within a few days of their preparation.


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