scholarly journals STUDIES ON BACILLUS TYPHOSUS TOXIC SUBSTANCES

1929 ◽  
Vol 50 (4) ◽  
pp. 513-520 ◽  
Author(s):  
Gregory Shwartzman

It has been demonstrated that many multiples of minimal doses of Bacillus typhosus reacting factors can be neutralized by specific immune sera. The potency of a given serum can be conveniently titrated against increasing amounts of reacting factors. If the immune serum is diluted or if the amount of the reacting factors is too large for a given amount of serum, there is obtained neutralization but only irregularly. Normal and heterologous sera (therapeutic meningococcus and erysipelas horse sera) free of normal agglutinins or possessing normal agglutinins of a low titer (1:16) for Bacillus typhosus are not able to neutralize the reacting factors. There is obtained questionable neutralization with a serum possessing normal Bacillus typhosus agglutinins in dilution 1:64. The titer of the neutralizing antibodies increases in the course of immunization. Immune sera exercise a definite protection against the mortality induced by intravenous injection of Bacillus typhosus culture filtrates.

1929 ◽  
Vol 50 (4) ◽  
pp. 521-531 ◽  
Author(s):  
Walther F. Goebel ◽  
Oswald T. Avery

It has been demonstrated that many multiples of minimal doses of Bacillus typhosus reacting factors can be neutralized by specific immune sera. The potency of a given serum can be conveniently titrated against increasing amounts of reacting factors. If the immune serum is diluted or if the amount of the reacting factors is too large for a given amount of serum, there is obtained neutralization but only irregularly. Normal and heterologous sera (therapeutic meningococcus and erysipelas horse sera) free of normal agglutinins or possessing normal agglutinins of a low titer (1:16) for Bacillus typhosus are not able to neutralize the reacting factors. There is obtained questionable neutralization with a serum possessing normal Bacillus typhosus agglutinins in dilution 1:64. The titer of the neutralizing antibodies increases in the course of immunization. Immune sera exercise a definite protection against the mortality induced by intravenous injection of Bacillus typhosus culture filtrates.


1931 ◽  
Vol 54 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Gregory Shwartzman

It has proved possible to elicit passive immunity to B. typhosus reacting factors by means of normal and immune homologous neutralizing antibodies. The in vivo serum protection against these factors followed the law of multiple proportions. There was observed a considerable loss of antibodies from the blood stream. Passive immunity was best obtained when the immune serum was injected intravenously ½ hour before the intravenous injection of the reacting factors. It was possible to prevent the occurrence of the local skin reaction by an intravenous injection of serum after the intravenous injection of the reacting factors, provided the serum dose was very large and provided the serum injection was made immediately after the filtrate injection. A number of experiments clearly demonstrated the interesting fact that the greater the amount of antiserum injected intravenously, the more efficient was the in vivo neutralization, in a ratio distinctly greater than the quantitative increase of serum. It is suggested that there may be a practical value of the observation in relation to serum therapy. The results also demonstrated passive serum protection against the lethal effect of B. typhosus "agar washings" filtrates, in a ratio which seemed to suggest the law of multiple proportions.


1912 ◽  
Vol 16 (1) ◽  
pp. 78-102 ◽  
Author(s):  
Augustus B. Wadsworth

From the results of this study of the action of immune sera on pneumococcus infection it is evident that immune sera vary greatly in their curative value. Immune sera possess protective action, but protective action is not necessarily indicative of curative action. Treatment with the serum of normal rabbits may prolong the course of pneumococcus infection in the rabbit. This action, however, is slight and not always manifest. Sera from animals immunized with dead pneumococcus cells which had been washed free from their products, failed to exert materially greater curative action than normal sera. Sera from animals immunized with culture filtrates free from pneumococcus cells possessed, in some instances, a slight curative value, but often this curative action was not apparent. In animals actively immunized, however, the presence of an immunity to culture filtrates was readily demonstrated. In the immunity produced by injections of dead culture material the strength was not sufficiently exalted for the sera to possess a practical curative value. It was only after immunization with virulent living cultures that the blood serum acquired marked curative action. After pneumococcus infection in the rabbit had become established, treatment with this serum induced crisis and cured the animals. From the results of the study of the mechanism of recovery it is evident that, despite the fact that virulent pneumococci are singularly insusceptible to the action of immune sera in the test-tube, pneumococcus infection nevertheless conforms to the general law of infection. Diphtheria and tetanus organisms give rise to powerful toxins, but the parasitism of these organisms is slight and their development is localized. Diseases produced by these organisms are toxemias and neutralization of their toxins by antitoxin puts an end to the disease. The pneumococcus gives rise to toxic substances which are less active or are active only in the body tissues, but the parasitism of this organism is marked and its development is rarely localized. Nevertheless, the manifestations of the disease arise from the action of the bacterial poisons on the tissues. The neutralization of the pneumococcus poisons by immune serum puts an end to the symptoms of the disease, but the pneumococci survive as harmless parasites until destroyed by lysis or phagocytosis. The neutralization of the pneumococcus poison may take place suddenly and completely as in crises; or, it may be incomplete with exacerbations of infection, as in lysis. Crisis, as it occurs in the lobar pneumonia of man and in the bacteriemia of the rabbit, is simply one phase of recovery, and recovery does not differ fundamentally, whether it is sudden and complete as in crisis, or incomplete and prolonged as in lysis, or whether the pneumococci are destroyed by lysis extracellularly as in the rabbit, or intracellularly as in the phagocytosis of the dog and man. Since the recovery of animals from pneumococcus infection differs in no essential from that of man, since the unaided protective mechanism of man as compared with that of susceptible animals is exceptionally efficient, and since it is possible by treatment with sera from animals highly immunized with living cultures of virulent pneumococci to cure pneumococcus infection in the most susceptible animals, it is difficult to conceive of the infection in man failing to yield similarly to the administration of such sera.


1935 ◽  
Vol 61 (3) ◽  
pp. 369-382 ◽  
Author(s):  
Gregory Shwartzman

New toxic substances in certain tuberculin, O.T., and B. typhosus culture filtrates are described. These substances are capable of eliciting the hemorrhagic necrosis characteristic of the phenomenon of local skin reactivity provided heterologous bacterial filtrates of high potency are used either for the intradermal or the intravenous injection. The toxic substances apparently have no relationship to the tuberculin substances proper. The experiments with inactive preparations also demonstrate in rabbits a state of hypersensitiveness to tuberculin, O.T., and bacteria-free culture filtrates in the absence of tuberculous foci. The reactions are elicited provided the tissues are rendered vulnerable through contact with certain soluble bacterial factors capable of eliciting the phenomenon of local skin reactivity to bacterial filtrates, and provided the tuberculin or the tuberculous culture filtrates are injected intravenously into immunized rabbits.


2007 ◽  
Vol 82 (3) ◽  
pp. 1332-1338 ◽  
Author(s):  
Jay W. Hooper ◽  
Anthony M. Ferro ◽  
Victoria Wahl-Jensen

ABSTRACT Hantavirus pulmonary syndrome (HPS) is a highly pathogenic disease (40% case fatality rate) carried by rodents chronically infected with certain viruses within the genus Hantavirus of the family Bunyaviridae. The primary mode of transmission to humans is thought to be inhalation of excreta from infected rodents; however, ingestion of contaminated material and rodent bites are also possible modes of transmission. Person-to-person transmission of HPS caused by one species of hantavirus, Andes virus (ANDV), has been reported. Previously, we reported that ANDV injected intramuscularly causes a disease in Syrian hamsters that closely resembles HPS in humans. Here we tested whether ANDV was lethal in hamsters when it was administered by routes that more accurately model the most common routes of human infection, i.e., the subcutaneous, intranasal, and intragastric routes. We discovered that ANDV was lethal by all three routes. Remarkably, even at very low doses, ANDV was highly pathogenic when it was introduced by the mucosal routes (50% lethal dose [LD50], ∼100 PFU). We performed passive transfer experiments to test the capacity of neutralizing antibodies to protect against lethal intranasal challenge. The neutralizing antibodies used in these experiments were produced in rabbits vaccinated by electroporation with a previously described ANDV M gene-based DNA vaccine, pWRG/AND-M. Hamsters that were administered immune serum on days −1 and +5 relative to challenge were protected against intranasal challenge (21 LD50). These findings demonstrate the utility of using the ANDV hamster model to study transmission across mucosal barriers and provide evidence that neutralizing antibodies produced by DNA vaccine technology can be used to protect against challenge by the respiratory route.


1926 ◽  
Vol 43 (6) ◽  
pp. 785-795 ◽  
Author(s):  
E. E. Ecker ◽  
A. Rademaekers

Following intravenous injection, filtrates of young cultures of B. paratyphosus B often produce marked diarrhea in rabbits. A study was made of the effect of these toxic filtrates on the motility of the small intestines of the rabbit. The observations were made on a segment of the small intestines in situ, and in the living animal. It was found that an immediate slight rise of tone of the longitudinal muscles occurred following intravenous injection of sterile broth. The same rise was noted after the injection of the toxic filtrate; but with these it was followed later (10 minutes elapsing at least) by a very strong but gradual rise of the diastolic and systolic tone, i.e., by spasmodic contraction of the intestinal muscle, which persisted at times for as long as 2 hours. In order to record simultaneously the effect on the longitudinal and circular muscles, and the propulsive efficiency of the segment the Sollmann and Rademaekers modification of Baur's technique was employed. This arrangement showed that the stimulation of the longitudinal muscles is accompanied by a similarly strong stimulation of the circular muscles, by peristalsis, and therefore by a greatly increased propulsion of intestinal contents which was sufficient to overcome the inhibition that usually occurs after preparation of the animal. With this arrangement an instance of peristaltic spasm was also noted. Broth alone failed to produce the phenomenon. Isotonic magnesium chloride or sulfate added to the bath relaxed the muscles again. Animals under deep urethane anesthesia did not show the diarrhea occurring in the intact controls, but sometimes exhibited it after the effect of the anesthetic had disappeared. So far no effects have been observed on the isolated strip (Magnus method), and further studies are being made to localize the effect, to neutralize it with a specific antiserum, and to observe the effect of filtrates of other members of the bacterial group including the dysentery bacilli.


1985 ◽  
Vol 31 (12) ◽  
pp. 1152-1156
Author(s):  
Thomas Fitzgerald

The in vitro effects of antibodies, complement, and (or) macrophages on Treponema pallidum have been previously characterized using relatively simple systems of organisms incubated with the immune components. In vivo, the more complex environment may alter immune reactivity. Experiments were performed to determine whether immobilizing and neutralizing antibodies retained their effectiveness in a more complex environment involving cultured mammalian cells. Two different protocols were used. In protocol A treponemes and normal or immune serum were mixed and added immediately to the cultured cells. In protocol B treponemes were preincubated for 18 h with cultured cells to maximize treponemal attachment; then normal or immune serum was added. With both protocols, attachment of organisms resulted in less effecient immobilization and neutralization. In further experiments, cultured cells were disrupted with Triton X, leaving cytoskeletal remnants on the vessel surface. Identical immobilization and neutralization experiments were performed in the presence of these remnants. In contrast to the findings with viable cultured cells, treponemal attachment to these nonviable remnants did not effect either antibody reaction. Attached organisms were immobilized or neutralized just as efficiently as unattached organisms. Results are discussed in terms of the altered immune reactivity in more complex in vitro environments.


1934 ◽  
Vol 59 (1) ◽  
pp. 83-95 ◽  
Author(s):  
Julia T. Weld

1. A method is described whereby toxic substances may be extracted from hemolytic streptococci with inactivated serum. 2. Such extracts contain large amounts of hemotoxin and leucocidin. 3. Their intravenous injection into mice causes marked hemoglobinuria, anemia, and death. 4. There is evidence that this anemia is not the only cause of death of these animals. 5. Incomplete work seems to indicate that the hemotoxin and the lethal poisons are not antigenic. 6. Certain biological properties of the extract are described.


1914 ◽  
Vol 20 (2) ◽  
pp. 169-179 ◽  
Author(s):  
Moyer S. Fleisher ◽  
Leo Loeb

Through the intravenous injection of various substances differing very much in character, multiple necrosis can be produced in the liver of the guinea pig. In the mouse the effect of these substances is absent or much less marked. Different substances seem to differ, however, in their power to produce necrosis. In control animals necrosis in the liver is much more rare. It is found especially in animals subjected to various injurious influences. The necrotic areas are usually situated between the portal and central areas of the liver acini. Their development is not due to thromboses interfering with the circulation in certain areas of the liver. They are probably due to a weakening of the circulation in the liver or to interference with the metabolism of the cells as a result of the injection of foreign substances. Mechanical factors (pressure on the liver cells) may have an additional effect. This necrosis may be compared etiologically to the acute gastric ulcers which can be produced through a great variety of toxic substances in the guinea pig.


1950 ◽  
Vol 92 (5) ◽  
pp. 463-482 ◽  
Author(s):  
Joseph L. Melnick ◽  
Nada Ledinko

The neutralization test is a reliable and useful procedure for following immunological reactions of the Coxsackie viruses (C virus). The standard procedure has been an incubation period of 1 hour at room temperature followed by subcutaneous inoculation into newborn mice. However, this time and temperature are not critical, for the virus in neutralized within 10 minutes of mixing with immune serum and remains neutralized for long periods. During the variable incubation periods used, the control virus remained active, even in dilute suspensions. The neutralization test is not affected by the presence or absence of complement. Neutralizing antibody is stable at 65°C. for 30 minutes, and immune serum has to be heated to 80°C. for 30 minutes before the antibody is no longer detectable. As the quantity of virus is increased, the quantity of serum required for neutralization likewise increases, but not in a regular or predictable fashion. Neutralized mixtures of the virus can be made infective again by simple dilution before inoculation. The neutralization test is a satisfactory means for typing Coxsackie viruses. At least seven antigenic types have been identified. Similar antigenic types have been found to be scattered over wide areas. Thus the Conn.-5 type was present in 1948 in Massachusetts, Connecticut, New York, and North Carolina. The Texas-1 type was present in 1943 in Connecticut and in 1948 in North Carolina and Texas. Further information on the specificity of the neutralizing antibody response has been obtained from a study of the occurrence and development of antibodies in 6 patients who contracted infections with one or another of the C viruses while working with them in the laboratory. From each patient a virus was isolated during the illness. No patient had detectable antibodies to his strain before his illness, but each soon thereafter developed antibodies to his own strain and to the prototype strain to which it was related. By means of the neutralization test, it has been shown that a family epidemic may include two different immunological types of virus. Neutralizing antibodies appear at the time of or soon after onset of illness, increase rapidly to titers of about 1:1000 which are maintained during the period of 1 to 3 months following infection, and are still present 2 years later, although at lower levels. Neutralizing antibodies are present in the normal population. In North Carolina, over 80 per cent of the children have antibodies at birth. The level falls rapidly to a minimum of 14 per cent at the age of 1, and then it quickly rises to reach the adult level at the age of 7. Gamma globulin collected in various parts of the United States between 1944 and 1949 and in Denmark in 1949 neutralizes at least four antigenically different Coxsackie viruses.


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