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R Dubos

Publications and source records attributed to R Dubos.

At least 37 records · Page 2Linked to original sources

The spaceship earth.

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Adaptation, Physiological↗

Human ecology.

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Adaptation, Biological↗

Lasting biological effects of early environmental influence. 3. Metabolic responses of mice to neonatal infection with a filterable weight-depressing agent.

A lasting depression of body weight was consistently produced in SPF mice by infecting them orally 2 days after birth with a nonlethal, bacteria-free filtrate, prepared from the intestine of young SPF mice previously infected with an unidentified agent. Neonatal infection caused a decrease of muscle DNA and of muscle and brain protein in the adults. No other effect was detected in the chemical composition of various organs. Incorporation of (14)C-amino acid into the acid precipitable fractions of liver, kidney, muscle, and brain was lower in infected than in control animals. No difference in incorporation was recognized in the thymus and spleen. The free amino acid pool of adults, measured as blood levels of free amino nitrogen, was decreased by neonatal infection. Surprisingly, the food intake of young animals infected neonatally was higher than that of the controls, measured on the basis of body weight. Their fecal excretion of nitrogen was also higher. The comparative responses of infected and control adults to a stressful situation was measured by giving them intravenously the antituberculous vaccine BCG. Under these conditions, the mice infected neonatally excreted some 20% more nitrogen in their urine and 40% more in their feces than did the controls. The mechanisms through which neonatal infection caused a lasting weight depression are discussed in the light of these metabolic findings.

Amino Acids↗

Alterations in the mouse cecum and its flora produced by antibacterial drugs.

Addition of penicillin, Terramycin, or kanamycin to the drinking water of adult mice rapidly induced in them an enlargement of the cecum. In all animals, this occurred within 12 hr after the beginning of drug administration-the effect being most pronounced with penicillin. The cecums remained enlarged and generally continued to increase in size as long as the antibacterial drugs were administered. The increase in wet weight of the cecums was due primarily to an accumulation of water in the lumens during the first 24-48 hr of drug administration. At that time, there were no detectable histological changes in any case, but the bacteriological picture differed from drug to drug. The cecums were free of bacteria in animals receiving penicillin, fusiform-shaped bacteria and bacteroides were present in those receiving Terramycin, and lactobacilli and bacteroides in those receiving kanamycin. After the initial 48 hr, an abundant and complex secondary microflora developed in all treated animals, its composition being characteristic for each type of antibacterial drug. When penicillin was administered for 2 wk, the cecal weights and microbial populations did not return to normal levels for over 14 days after discontinuance of the drug. This recovery period could be shortened to 10 days by giving the mice food contaminated with cecal homogenates prepared from normal animals. A period of 7 or 8 days was required for the cecal weights and microflora to reach normal levels when the administration of penicillin lasted only 24 hr; this period could not be shortened by giving the animals contaminated food. The effects of drugs on the size and bacterial contents of the cecum have been discussed in the light of earlier findings concerning the characteristics of the huge cecums uniformly found in germfree mice. Taken together, these observations support the hypothesis that certain elements of the intestinal microflora-not yet completely identified-play an essential role in maintaining the integrity of the water-transport mechanism in the intestinal epithelium.

Animals↗

Lasting biological effects of early environmental influences. I. Conditioning of adult size by prenatal and postnatal nutrition.

Newborn specific-pathogen-free mice (SPF) were separated from their mothers shortly after birth and immediately reallocated at random to foster mothers, each of which received eight young. Under these conditions, the growth rate and adult size of the young were profoundly and lastingly conditioned by some unidentified influence exerted by the foster mother. In SPF mice nursed by their own mothers, the diet of the latter during gestation and lactation, or during lactation alone, conditioned the weight of the young at weaning time, and throughout their whole life span. Lasting depression of growth has been achieved by minor alterations of the dam's diet, for example by lowering its content in magnesium, or in lysine and threonine. The growth-depressing effect so achieved persisted throughout the whole life-span of the young, even though they were given at weaning time and constantly thereafter unlimited amounts of an optimum diet. In contrast, the weight-depressing effect of a diet deficient in lysine and threonine administered to adult animals was completely and rapidly reversible when a complete diet was later substituted for the deficient one. Depression of growth resulting from nutritional experiences during gestation or lactation did not seem to affect adversely the health of the young, or to decrease their longevity. In fact, the results of two experiments in which the animals nursed by mothers on different diets, were kept undisturbed and on optimum diets throughout their whole life span, suggest that the smaller animals had a greater average life expectancy than the larger ones.

Animals↗

Lasting biological effects of early environmental influences. II. Lasting depression of weight caused by neonatal contamination.

Certain specific-pathogen-free (SPF) mice bred and maintained under semiprotected conditions have an intestinal flora which is qualitatively simpler (although not quantitatively smaller) than that of mice of the same genetic stock produced under ordinary conditions. They are also heavier at weaning time, grow at a faster rate, and reach a greater adult weight than ordinary mice. When SPF mice are contaminated per os shortly after birth with certain bacterial cultures isolated from the intestinal contents of adult ordinary mice, these bacteria multiply extensively throughout the gastrointestinal tract and persist at extremely high levels until weaning time. Such bacterial infections do not affect significantly either weaning weight, growth rate, or maximum adult weight. In contrast, weight depression could be consistently brought about by contaminating newborn SPF mice per os with bacteria-free filtrates of homogenates of intestines from ordinary mice. The weight-depressing agent passed through Millipore discs of 0.45 and 0.22 micro porosity, but was held back at 0.10 micro porosity. The depression of weight caused by either intestine homogenate or filtrates thereof could be detected within a few days after contamination (of 2 day old mice) and persisted throughout the adult life of the contaminated animals. When intestine homogenate of the SPF mice used in this study were introduced per os into newborn SPF mice, they did not affect their growth rate or adult weight. On several occasions, but not consistently, bacteria-free filtrates capable of depressing the weight curve of SPF mice produced alterations in the appearance of tissue cultures of BHK-21 and mouse embryo cells. When tissue cultures so infected were introduced into newborn SPF mice, the weight of these animals was depressed early and lastingly. An agent exhibiting weight-depressing activity has been transferred from mouse to mouse over many passages by contaminating newborn SPF animals per os. Weight depression was achieved with extremely small doses of material (10(-5) ml of intestine homogenate of 10(-4) of mouse embryo culture). Under these conditions, none of the animals showed obvious signs of disease except reduced weight. Only very young SPF mice (preferably less than 3 days old) proved susceptible to the weight-depressing effect of the filtrates of intestine homogenates or of infected tissue cultures prepared therefrom. After oral contamination, it took approximately 1 wk before the intestinal homogenate obtained from contaminated animals exhibited a high level of weight-depressing activity. The growth-depressing effect could be transmitted from one generation to the next by mating SPF mice that had been contaminated shortly after birth and that were consequently smaller than control SPF animals.

Animals↗

The gastrointestinal epithelium and its autochthonous bacterial flora.

Colonization of the gastrointestinal tract by bacteria of the normal flora was followed by bacteriological and special histological techniques in mice from several colonies. These histological techniques were designed to preserve the intimate associations that become established between particular strains of microorganisms and the epithelium of the mucosa of certain areas of the gut. The findings were as follows: 1. The various strains of bacteria of the normal flora became established in the different areas of the guts of infant mice according to a definite time sequence. 2. The first types of bacteria that could be cultured from the gut were lactobacilli and Group N streptococci. Within the first day after birth, these bacteria colonized the entire digestive tract and formed layers on the stratified squamous epithelium of the nonsecreting portion of the stomach and of the distal esophagus. 3. The bacterial types that appeared next were coliforms and enterococci. From about the 9th to the 18th day after birth, these bacteria could be cultured in extremely high numbers from the cecum and the colon. Histological sections of those organs taken during the first 2 or 3 days of that interval revealed microcolonies of Gram-positive cocci in pairs and tiny Gram-negative rods embedded in the mucous layer of the epithelium. The microcolonies were well separated from the mixture of digesta and bacteria that occupied the center of the lumen; they may have consisted of the coliforms and enterococci mentioned above; but this possibility remains to be proved. 4. Histological sections also revealed that, at about the 12th day after birth, long, thin Gram-variable rods with tapering ends were present, side by side, with the small Gram-negative rods and Gram-positive cocci in the mucous layer. By the 15th day after birth, the fusiform bacteria formed thick layers in the mucus, and seemed to be the only bacteria remaining in that location. It has not yet been possible to enumerate these tapered rods by culture methods, but as judged by visual appearances in the histological sections, they seemed to outnumber all other bacteria in the cecum and the colon by a factor of as much as 1000. It must be stressed that these bacterial layers are readily disrupted and even washed away by conventional histological techniques; their discovery was largely due to the use of the special histological techniques described in the text. The bacteriological and histological findings described here constitute further evidence for the hypothesis that symbiotic associations exist between microorganisms and animals, and that a very large percentage of the bacteria in the gastrointestinal tract constitutes a true autochthonous flora. The constant occurrence of several distinct associations of bacteria with the special histological structures of the animal host renders obsolete the notion that the intestine constitutes a chemostat in which the bacterial populations are randomly mixed. For a full understanding of the ecology of the normal microflora, it is necessary to think of body surfaces as distinct microenvironments in which virtually pure cultures of a few species of microorganisms interact with their host and the adjacent microbial populations. Experiments based on this hypothesis are admittedly difficult to design, but on the other hand studies based on the assumption that microorganisms exist as mixtures in the gastrointestinal tract will be only of limited value and may often be misleading.

Animals↗

Humanistic biology.

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Adaptation, Biological↗

Coliform bacteria in the intestine of mice.

Mice of the NCS and NCS-D colonies, bred at the Rockefeller University, harbored in their intestine an endemic strain of slow lactose-fermenting Escherichia coli 081+/-: :H21 serotype. In addition, NCS mice have recently acquired E. coli 0109+/-:K48:H14. Both strains persisted during the period of observation, whereas they were not encountered in the feces of mice from two other colonies. Other coliform strains encountered were more transient in their occurrence. Since strains of E. coli 081+/-: :H21 and 0109+/-:K48:H14 are extremely uncommon in human beings, it seems probable that they possess specificity for the mouse host.

Absorption↗

The influence of endotoxin administration on the nutritional requirements of mice.

Albino mice lose weight within 24 hours following administration of bacterial endotoxin. The initial weight loss is proportional to the dose of endotoxin injected only when this dose is very small. The loss during the 1st day reaches a maximum with 10 to 30 microg of endotoxin; larger doses increase the duration of the overall effect. The rate at which mice regain weight after administration of endotoxin is markedly influenced by the composition of the diet. Recovery was rapid and complete within a few days when the animals were fed commercial pellets or a semisynthetic diet containing casein. In contrast, recovery was slow and incomplete when wheat gluten was used instead of casein in the diet. The deleterious effect of the gluten diet was less marked in older than in younger animals, probably because the latter have less exacting nutritional requirements. It was postulated that the failure of endotoxin-treated mice to regain weight when fed the gluten diet was due to the fact that this protein is low in certain amino acids. In fact, rapid and complete recovery from the weight loss uniformly occurred when the gluten diet was supplemented with proper amounts of lysine and threonine. The composition of the diet did not influence the extent of the initial loss of weight caused by endotoxin, nor did it prevent the animals from developing tolerance to this substance.

Aging↗