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Biomedical subjects

R J DUBOS

Publications and source records attributed to R J DUBOS.

At least 37 records · Page 2Linked to original sources
PubMed1958

The effect of bacterial constituents on the resistance of mice to heterologous infection and on the activity of their reticulo-endothelial system.

Administration of small amounts of salmonella endotoxin (20 microg.) or of acetone-extracted BCG cells (100 microg.) increases the resistance of mice to infection with Myco. fortuitum as well as their ability to clear carbon particles from their blood stream. Whereas the increased resistance to infection persists for many weeks, the clearing power returns to a normal level within a few days. When normal mice are infected with Myco. fortuitum, there occurs during the first phase of the infectious process a rise in clearing power for carbon particles followed by a fall during the terminal phase of the disease. The rise occurs more rapidly and is more pronounced in animals previously treated with salmonella endotoxin or with killed BCG cells. This acceleration and intensification of the phagocytic response to infection can be detected even in animals which exhibit a normal phagocytic index when tested several weeks after administration of endotoxin or of BCG. Although increase in resistance to infection is correlated with activation of the so called reticulo-endothelial system, there is no evidence of any direct causal relationship between the two phenomena.

Animals↗
PubMed1957

Effects of cellular constituents of mycobacteria on the resistance of mice to heterologous infections I. Protective effects.

Vaccination with living attenuated tubercle bacilli (BCG) was found to increase the resistance of mice to infection with virulent staphylococci. An even more striking protective effect could be elicited by intraperitoneal or subcutaneous injection of small amounts (0.1 mg. or more) of killed BCG cells. The killed BCG cells retained most of their protective activity after prolonged heating at acid, neutral, or basic reactions-and after extraction with acetone, methanol, and NaOH (at pH 10.5). Some protective activity could be recovered in a fraction soluble in methanol at 55 degrees C. The protective effect against infection manifested itself in a prolongation of survival time following infection, and also in the fact that smaller numbers of staphylococci were recovered from the organs of infected mice. Both types of effects were still evident 10 weeks after vaccination. Injection by the intraperitoneal route of killed cells of BCG, or of methanol extracts of them, elicited in mice a high level of protection against intravenous injection of Myco. fortuitum. A protective effect quantitatively and qualitatively similar to that elicited by BCG, resulted from the intraperitoneal or subcutaneous injection of killed cells of Myco. fortuitum.

Animals↗
PubMed1957

Effects of cellular constituents of mycobacteria on the resistance of mice to heterologous infections. II. Enhancement of infection.

Injection of certain cellular constituents of mycobacteria into mice simultaneously with, or shortly after, infection with Staph. aureus or with Myco. fortuitum, markedly shortened the life of the infected animals. This infection-enhancing effect could be achieved by injecting the cellular constituents by either the intravenous, the intraperitoneal, or the subcutaneous route. Suspensions of killed mycobacteria were injected into mice which had been infected several months before with small doses of various bacterial pathogens and which still harbored small numbers of living organisms in their organs. Under these conditions, a marked increase in the numbers of living bacteria in the organs of the treated mice could be detected within a very few days after treatment with the mycobacterial products, and a certain percentage of the animals died rapidly. One of the first and most constant manifestations of the change in the infectious process from the chronic to the acute state was the appearance of a large microbial population in the liver. This happened even though Staph. aureus and Myco. fortuitum are rapidly cleared from the liver of normal mice. In addition to killed cells of BCG and of Myco. fortuitum, pertussis vaccine and the purified lipopolysaccharide (endotoxin) of Gram-negative bacilli also proved capable of converting chronic bacterial infections into acute infectious processes.

Animals↗
PubMed1957

Tice strain of BCG.

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Mycobacterium bovis↗
PubMed1956

Reversible changes in the susceptibility of mice to bacterial infections. I. Changes brought about by injection of pertussis vaccine or of bacterial endotoxins.

MICE WERE INJECTED INTRAPERITONEALLY WITH ONE OF THE FOLLOWING BACTERIAL PRODUCTS HAVING ENDOTOXIN ACTIVITY: pertussis vaccine, a suspension of heat-killed cells of Klebsiella pneumoniae (type C), or a purified lipopolysaccharide prepared from cultures of Salmonella typhosa. Following treatment with either one of these materials, the animals were infected intravenously with virulent cultures of coagulase-positive staphylococci, with bovine tubercle bacilli, or Friedländer bacilli. The effect of treatment with endotoxin materials on resistance to Friedländer bacilli, staphylococci, or tubercle bacilli was estimated by observing the mortality rates in infected animals, and by determining quantitatively the numbers of living bacteria in the organs at different periods of time after infection. It was found that mice receiving the infective dose of virulent culture a few hours after treatment with the endotoxin material, were usually more susceptible to infection than were untreated animals. In contrast, mice infected at a later period proved far more resistant to infection than did untreated animals. The duration of the negative and of the positive phase of resistance was affected by the amount of endotoxin injected. Marked increase in resistance of mice to infection with staphylococci or tubercle bacilli was still evident several weeks after treatment with pertussis vaccine or with purified lipopolysaccharide extracted from typhoid bacilli.

Animals↗
PubMed1956

Reversible changes in the susceptibility of mice to bacterial infections. II. Changes brought about by nutritional disturbances.

A study has been made of the time variations in the susceptibility of albino mice to experimental infections with Klebsiella pneumoniae, Staphylococcus aureus, and Mycobacterium tuberculosis. Susceptibility to infection was determined by two criteria: (a) mortality rates following intravenous injection of a known infective dose; (b) numbers of bacterial colonies that could be recovered from the tissues of the infected animals at various times after infection. When measured in terms of either one of these two criteria, susceptibility was consistently modified by temporary deprivation of food, and by various changes in the composition of the diet. Increase in susceptibility to infection could be detected within a few hours to a few days depending upon the nature and intensity of the nutritional disturbance imposed upon the animal. Under the proper conditions, return to a normal state of resistance could also occur within a very short time. There was commonly observed an explosive bacterial multiplication in mice receiving the infective dose shortly after being subjected to nutritional disturbances. In the case of infection with Klebsiella pneumoniae, however, this phase of increased susceptibility was often followed a few hours later by one during which the numbers of living bacteria that could be recovered from the various organs fell to a very low level. Many of the animals which had exhibited severe but transient bacteriemia recovered rapidly and survived the infection. Mice rendered more susceptible to infection by being fed deficient diets progressively recovered their normal resistance while being kept on the same inadequate regimens. This adaptation occurred even though the weight of the animals on these regimens remained much lower than the weight of the animals fed a complete diet ad lib. The weight of the animal at the time of infection appeared to have little bearing on susceptibility. However, susceptibility consistently increased during the periods while the animals were losing weight-whatever the cause of the weight loss. The facts disclosed in the present study, as well as findings reported by other investigators, make clear that profound changes in susceptibility to infection can be brought about by varied non-specific procedures. These changes can occur within very short periods of time and are often rapidly reversible.

Animals↗
PubMed1956

The effect of nutritional disturbances on the susceptibility of mice to staphylococcal infections.

The susceptibility of mice to intravenous injection of coagulase-positive hemolytic staphylococci was estimated by (a) observing the extent and time of mortality of infected animals; (b) determining the number of colonies of cocci that could be recovered from the liver and spleen at various intervals of time after infection. Complete deprival of food for 36 to 48 hours immediately before infection was found to increase susceptibility. This infection-enhancing effect was further increased by allowing the animals to drink a 5 per cent glucose solution instead of water or saline during the fasting period. In contrast, sodium lactate partially corrected the effect of fasting. The infection-enhancing effect of fasting was reversible. Mice prevented from gaining weight for several weeks either by restricting their daily food intake, or by feeding them ad lib. an inadequate diet, appeared just as resistant to staphylococcal infection as did mice that gained weight rapidly on an unrestricted, complete diet.

Animals↗
PubMed1956

The effect of dinitrophenol and thyroxin on the susceptibility of mice to staphylococcal infections.

Mice were given daily per os amounts of dinitrophenol or of thyroid extract sufficient to prevent or retard the normal weight gain of uninfected animals, but not large enough to cause their death. When mice maintained on these regimens for 1 or 2 weeks were infected with staphylococci, most of them died within 12 days-much more rapidly than did mice fed a normal diet. Deaths occurred even when the organism injected was a non-virulent staphylococcus, unable to cause fatal disease in mice fed a normal diet. There was some suggestion that thyroid treatment interfered with the bactericidal mechanism in the liver, spleen, and kidneys of mice during the initial phase of infection. In contrast there was no clear evidence at any time thereafter that either thyroid extract or dinitrophenol caused the staphylococci to multiply more rapidly in the various organs.

Animals↗
PubMed1956

Antituberculous immunity induced by methanol extracts of tubercle bacilli; its enhancement by adjuvants.

It is possible to prepare from tubercle bacilli a fraction soluble in methanol which is capable of eliciting in mice a marked degree of resistance against virulent tuberculous infection. The immunity was evident whether the infective dose was large and caused a disease with a rapid course, or was very small and caused a disease of many months duration. Active material has been obtained by extraction with methanol at 55 degrees C. of bacterial cells killed with 2 per cent phenol, and washed with acetone. The methanol extracts used in the present study have been prepared from the phenol-killed cells of a culture of BCG, and of the avirulent culture H37Ra. Vaccination of mice bas been carried out by the intraperitoneal route, and the challenge infection (with a highly virulent bovine culture), by the intravenous route. Weight for weight, the protective activity of the methanol extract is smaller than that of the bacterial cells from which it is extracted, but its primary toxicity for mice is also considerably lower. The protective activity can be increased, and the immunity prolonged, by using certain adjuvants as vehicle for injection of the vaccine. An oil adjuvant mixture, and small amounts of a highly purified preparation of the somatic antigen of typhoid bacilli, have been found capable of enhancing and prolonging the antituberculous immunity induced by the methanol extract. Under appropriate conditions the resistance resulting from intraperitoneal injection of the methanol extract is of the same order as that which follows vaccination with whole killed tubercle bacilli or with living BCG.

Adjuvants, Immunologic↗
PubMed1956

The behavior of virulent and avirulent staphylococci in the tissues of normal mice.

The fate of hemolytic staphylococci injected intravenousiy into albino mice was followed by determining quantitatively the numbers of living organisms present in the various tissues at different intervals of time after infection. Irrespective of the strain of staphylococcus used, most of the organisms disappeared rapidly from the blood, liver, spleen, and kidneys. This was true even when the infective dose consisted of large numbers of virulent, coagulase-positive staphylococci, capable of producing a fatal disease in a high percentage of the infected mice. The initial rate of removal or destruction of staphylococci was particularly high in the lungs and kidneys. In all cases on the other hand, a few living staphylococci persisted in the various organs for several weeks after infection, even when the organisms were non-virulent and coagulase-negative. Although virulent as well as avirulent staphylococci were eliminated extremely rapidly and efficiently from the kidneys during the initial stage of infection, the microorganisms soon began to multiply in this organ, causing abscesses first detected in the cortex. Death of the animals infected with virulent cultures appeared to be due to the destruction of renal tissue by these abscesses. The abscesses caused by the avirulent strains eventually became sterile, and healed. No convincing difference could be recognized amongst seven strains in their resistance to the bactericidal power of the mouse tissues during the initial phase of the infection. In contrast, marked quantitative differences came to light in their subsequent behavior in the kidneys. The multiplication of the coagulase-negative staphylococci in this organ soon came to an end in all animals and never proceeded far enough to result in fatal disease. The staphylococci of a weakly coagulase-positive strain multiplied somewhat more extensively in the kidneys than did the coagulase-negative, but never sufficiently to cause the death of any animal within the period of observation of 1 month. The three coagulase-positive strains tested yielded the largest bacterial population in the kidneys and caused the death of many of the infected animals. These three virulent strains differed quantitatively amongst themselves with regard to both the rapidity and extent of their multiplication in the kidneys and the lethal power of a given infective dose. Taken together, the findings indicate that the hemolytic strains of staphylococci can be arranged in a continuous spectrum according to their ability to cause disease in albino mice. Although virulence for these animals appeared to be correlated with the production of coagulase, it did not seem to depend upon the ability of this substance to interfere with the bactericidal mechanisms of the mouse organs during the early phase of the infection. Virulence manifested itself chiefly by the production in the kidneys of progressive abscesses originating from the few staphylococci which were not destroyed during the initial bactericidal reaction.

Animals↗