The early events of experimental Brucella infection in the mouse. Relationships of bacteria with phagocytic cells and lymphoid tissue responses.
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Biomedical subjects
Publications and source records attributed to J Roux.
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Brucellosis is an anthropozoonosis, transmissable between animals and from animals to man. There is no interhuman transmission. Practically all domestic and wild animals are sensitive to various species of Brucella which explains the world-wide occurrence of the disease. Animals transmit the disease to man by direct contact (giving rise most often to professional disease which accounts for approximately 2/3 of the cases in France), and by way of food consumption (milk, cheese). The discovery of host animals may guide the diagnosis of human cases but more often the diagnosis of a human case reveals the existence of a host animal. Among the serological tests which help to follow the course of the human disease, the importance of the card test and of the immunofluorescence reaction are especially emphasized. The incidence of the human disease is difficult to determine: from the number of cases notified, the number of cases actually diagnosed can be estimated (from 3 to 5 times greater in France); however the true number of cases is very difficult to estimate owing to the large number of asymptomatic or atypical cases.
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A peptidoglycan-containing fraction called fraction P.I. (phenol insoluble), extracted from Brucella melitensis and previously described by some of us, had immunogenic and protective properties and did not produce any allergic reactions. Since it is well known that bacterial peptidoglycans studied so far have immunoadjuvant properties, the isolation of the active factor(s) of Brucella was undertaken. By successive enzymatic and chemical treatments, a new, much more purified fraction, called "4A" (approximately 5% of fraction P.I.), is obtained, retaining the same properties as P.I. and giving better protection against infection by Brucella. Immunogenicity, immunoadjuvant activity, allergizing capacity, and specific and nonspecific protective effects of fractions P.I. and 4A are compared. Chemically, fraction 4A is constituted by a lipoprotein covalently linked to peptidoglycan and by a few (lipo)proteins that could be solubilized by hot sodium dodecyl sulfate. Intrinsic properties of peptidoglycan could not be studied, but it does not seem to be essential for the activity. In conclusion, fractions P.I. and 4A are not agglutinogenic and, since fraction 4A induces better protection against infection by Brucella, it could advantageously replace fraction P.I. as a vaccine for humans.
The different forms of chronic brucellosis have been improved and well stabilized in the proportion of 75% by repeated injections of a vaccine consisting of suspensions of heat-killed B. melitensis. The vaccine should be used in a series of 8 subcutaneous injections, in increasing doses, at the rate of 2 injections a week. To obtain good results it is necessary to give an average of 3 to 4 series of injections, with a two months' interval between each series. After the 2nd series a distinct decrease of the patient's reactions to retarded hypersensitivity tests are generally observed. The most favourable results are obtained in cases of common subjective syndrome with physical and psychical asthenia.
A complex phenol-insoluble fraction (fraction P.I.) extracted from Brucella melitensis presents immunizing properties already described by the authors. This fraction contains peptidoglycane whose immuno-adjuvant properties are known in numerous bacterial species. More precise fractionation was carried out to determine if the properties observed after injection of P.I. are in fact specific or on the contrary due to peptidoglycane action. By chemical and enzymatic treatments, 90% of the P.I. are eliminated, leaving a 4A fraction having the same properties as P.I. and having the advantage of providing better protection. This protection specific to genus Brucella and slow in appearing, is not due to peptidoglycane. The 4A fraction consists essentially of peptidoglycane linked covalently with a lipoprotein and proteins of weak molecular weight. All attempts at more precise fractionation have until now led to the loss of biological activity.
Two children presented with an acute mycoplasma infection associated with a significant increase of antistreptolysin level. A severe nephropathy occurred, rapidly resulting in renal failure with histologic lesions of membrano-proliferative glomerulonephritis. Both patients had persisting low complement levels with low C3 and normal C4. The relationship between mycoplasma and streptococcal infections and the abnormality of complement and the renal disease is discussed.
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