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Biomedical subjects

R J DUBOS

Publications and source records attributed to R J DUBOS.

At least 55 records · Page 3Linked to original sources
PubMed1955

A fraction of tubercle bacilli possessing primary toxicity.

Tubercle bacilli separated from young cultures were thoroughly extracted with monochlorobenzene at temperatures never exceeding 50 degrees C. From the soluble material, a fraction corresponding to approximately 1 per cent of the total bacillary weight was separated by fractional precipitation with petrolic ether at temperatures of 0 degrees or 4 degrees C.-depending upon the strain of bacilli. The monochlorobenzene-soluble-ether-insoluble material (fraction 7) prepared from BCG-P was found to contain 0.14 per cent nitrogen and 0.4 per cent phosphorus. Some of its other chemical characteristics are described. Fraction 7 proved unable to elicit tuberculin allergy in guinea pigs, but injection of 5 microg. of it into the skin produced severe local reactions. In albino mice, a single intraperitoneal injection of 20 microg. caused loss of muscular tone and of weight followed by death within 9 days. The only tissue reaction observed was a slight degree of peritonitis. In mice of the C57 BL strain, a single injection of 40 microg. also caused death in the same time, but with pulmonary hemorrhages-usually massive. Material similar to fraction 7 was obtained from one virulent, two attenuated, and one avirulent strain of mammalian tubercle bacilli (bovine and human). The fractions obtained from the various strains differed somewhat in solubility and toxicity. The more virulent the culture, the more toxic was the fraction obtained from it; but it is possible that this relation was the result of differences in the effectiveness of the extraction procedures, rather than of characteristics inherent to the cultures. Evidence is presented that the toxicity of fraction 7 accounts for much of the primary toxicity of tubercle bacilli.

Animals↗
PubMed1955

Antituberculous immunity induced in mice by vaccination with killed tubercle bacilli or with a soluble bacillary extract.

It proved possible to increase the resistance of mice to tuberculous infection by vaccinating them with a suspension of avirulent tubercle bacilli killed by exposure to 2 per cent phenol. This increase in resistance was demonstrated by two different techniques: (a) observation of survival time of vaccinated animals following challenge infection with a large dose of virulent bacilli, and (b) determination of numbers of virulent bacilli in the spleens of animals 2 weeks after injection of a small infective dose. The minimum protective dose of vaccine corresponded to approximately one-tenth the acutely toxic dose. Addition of an adjuvant to the bacillary suspension markedly increased both the protective effectiveness of the vaccine and the duration of the immunity. It enhanced also the toxicity of the vaccine in approximately the same proportion. However, other lines of evidence suggested that toxicity and protective activity were independent one from the other and were the manifestations of different bacillary constituents. Extraction with absolute methanol released from the bacillary bodies a crude soluble fraction possessing low, if any, toxicity, yet capable of eliciting in mice a state of increased resistance to virulent infection. The protective activity of this methanol-soluble fraction was low; it accounted for only a small part of the total protective activity of the original material.

Adjuvants, Immunologic↗
PubMed1955

Effect of metabolic factors on the susceptibility of albino mice to experimental tuberculosis.

Mice maintained on various types of diets were found to become more susceptible to tuberculosis when deprived of food for periods of 30 hours shortly after infection. In contrast, the susceptibility of the animals to the disease was unaffected by undernutrition resulting from limitation of food intake to a low but constant daily level. The resistance of mice to tuberculosis appeared to be independent-within wide limits-of the protein content of the diet. It is true that mice fed a diet very low in protein and high in carbohydrate proved highly susceptible, but resistance was normal if part of the carbohydrate was replaced by fat (peanut oil)-without any change in the protein content of the food. Resistance to tuberculosis could be consistently and markedly decreased by adding sodium citrate (or glutarate) to a variety of diets. The survival time following infection was greatly shortened if dinitrophenol or thyroxine were administered per os in amounts sufficient to limit the weight gains of non-infected controls. There was usually a lag period of several days before the infection-enhancing effect of these metabolic stimulants became manifest. The procedures which increased the susceptibility of mice to infection with virulent tubercle bacilli also made it possible to establish in these animals a fatal infection with BCG. There was no constant relation between weight gains of uninfected mice on the various regimens, and the effect of the latter on susceptibility to tuberculosis. These findings appear compatible with, but do not prove, the hypothesis that a decrease in resistance to infection can be brought about by metabolic disturbances which cause either a depletion of the glycogen reserves of the body, or a reduction in the glycolytic activity of inflammatory cells, or an increase in the concentration of certain polycarboxylic acids and ketones in the tissues.

Animals↗
PubMed1954

The antimycobacterial activity of a peptide preparation derived from calf thymus.

A stable, water-soluble substance which possesses potent antimycobacterial activity under certain conditions in vitro has been prepared from calf thymus. This substance has been tentatively named thymus peptide. In final concentrations of 1 to 10 microg. per ml. of an albumin medium it inhibits the growth of various strains of mammalian mycobacteria, but manifests only little or no inhibitory activity against a variety of other microbial species. The ability of thymus peptide to inhibit the multiplication of tubercle bacilli diminishes when the inoculum is large, or when the medium is acidic. It is also markedly antagonized by addition of enzymatic hydrolysate of casein or beef heart infusion broth to the culture medium. Thymus peptide does not exert a rapid bactericidal action on tubercle bacilli, but organisms exposed to this compound for longer than 2 weeks could not be made to multiply in ordinary culture media. Substances similar or identical to the thymus peptide preparation could be extracted from calf spleen, sheep thymus, beef lymph nodes, and calf pancreas, but not from calf lung or calf liver.

Animals↗
PubMed1954

Chemical studies on a basic peptide preparation derived from calf thymus.

A substance possessing antimycobacterial activity under certain conditions in vitro has been prepared from aqueous extracts of calf thymus. Chemical studies have demonstrated that the activity of this substance is due to a basic peptide or a mixture of basic peptides. Although this thymus fraction has been shown to be essentially free of compounds other than peptides, it has not been obtained in a homogeneous state. The thymus peptide preparation is soluble in water and in the lower alcohols. Its solubility is minimal between pH 10 and 11, suggesting that its isoelectric point may be in this vicinity. The microbiological activity of thymus peptide is destroyed by acid or alkaline hydrolysis and also by trypsin digestion, but is unaffected by pepsin digestion. Cellulose membranes are permeable to thymus peptide. The most noteworthy finding concerning the amino acid composition of thymus peptide is the preponderance of the basic amino acids lysine and arginine, which together account for about 40 per cent of the weight of this substance. No cystine, and only trace amounts of other amino acids containing sulfur, are present in the thymus peptide preparation.

Amino Acids↗