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Biomedical subjects

M Parant

Publications and source records attributed to M Parant.

At least 55 records · Page 3Linked to original sources
PubMed1977

Immunological defect and its correction in the osteopetrotic mutant rat.

Congenital osteopetrosis in the mutant rat "op" is accompanied by early atrophy of the thymus gland. The response of thymocytes to concanavalin A and phytohemagglutinin P was greatly diminished at age 28 days, even before pronounced thymic atrophy could be detected. The response of spleen cells to mitogens that stimulate thymus-derived (T) and bone-marrow-derived (B) cells was diminished as early as 35 days of age. A single injection of a suspension of normal bone marrow, which cures osteopetrosis, increased thymus weight and restored the normal responses of both thymus and spleen to various mitogens. These results add further support to the hypothesis that the thymus is involved in the pathogenesis of osteopetrosis.

Age Factors↗
PubMed1977

Enhancement of nonspecific immunity to Klebsiella pneumoniae infection by a synthetic immunoadjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine) and several analogs.

N-Acetylmuramyl-L-alanyl-D-isoglutamine and four other synthetic adjuvants that are structural analogs of part of the mycobacterial peptidoglycan monomer are shown to enhance the nonspecific immunity of mice infected by Klebsiella pneumoniae. These compounds are active by various routes, including oral administration; they are also effective when administered after challenge. Of the seventeen other analogs tested, none is able to increase significantly resistance to infection, although seven of these molecules are adjuvant-active in saline. Previous results have shown that in contrast to lipopolysaccharides, these synthetic adjuvants are devoid of immunogenicity, mitogenicity, and toxicity in normal or adrenalectomized mice.

Adjuvants, Immunologic↗
PubMed1977

Enhancement of nonspecific immunity to bacterial infection by cord factor (6,6'-trehalose dimycolate).

The capacity of mycobacteria to enhance the nonspecific resistance of mice to bacterial infections was related to the presence of cord factor. After enzymatic digestion and delipidation, cell walls lost their immunopotentiating activity, which was restored, however, by the addition of cord factor. Cord factor administered alone protected mice effectively against virulent organisms unrelated to mycobacteria. Moreover, although this glycolipid is usually injected as a solution in mineral oil, our data show its effectiveness when administered in metabolizable peanut oil or even as a suspension in water. Since cord factor is a chemically well-defined molecule (6,6'-trehalose dimycolate), this glycolipid should constitute a new and useful tool for the investigation of nonspecific immunity to infection.

Animals↗
PubMed1977

Inheritance of lipopolysaccharide-enhanced nonspecific resistance to infection and of susceptibility to endotoxic shock in lipopolysaccharide low-responder mice.

In a previous study, we demonstrated that lipopolysaccharide (LPS) and other bacterial immunostimulants, in contrast to their activity in a closely related high-responder subline, failed to elicit nonspecific resistance in LPS low-responder mice against Klebsiella pneumoniae infection. To investigate the type of inheritance controlling the LPS-induced nonspecific resistance to infection, the present study was performed in low- and high-responder C3H sublines and in F1 and F2 hybrids. In addition, F1 mice were backcrossed to each parental type. Inheritance of susceptibility to endotoxin was also tested in both sublines and their hybrids and backcross progeny. For these latter assays, mice were previously adrenalectomized because removal of this gland considerably enhances their sensitivity. Our present findings are consistent with the hypothesis that LPS enhances nonspecific resistance to infection and that susceptibility to endotoxin shock in the absence of corticoids may be determined by a single autosomal dominant gene.

Adrenalectomy↗
PubMed1976

Role of B-lymphocytes in nonspecific resistance to Klebsiella pneumoniae infection of endotoxin-treated mice.

Lipopolysaccharides (LPS) of gram-negative bacilli are known to protect mice against unrelated bacterial infections and to be nonspecific mitogens of murine bone marrow-derived (B-) lymphocytes. For assessment of the role of these cells in the mechanism of LPS-induced resistance to infection with Klebsielia, various nontoxic mitogens were assayed. In contrast to LPS or lipid A, the nontoxic mitogens did not protect mice. Experiments were also performed with LPS in nude mice and in mice treated with immunosuppressants. Stimulation by LPS was decreased after administration of hydrocortisone or cyclophosphamide under conditions that inhibited the in vitro activation of lymphocytes by mitogens. Moreover, nude mice and mice treated with 6-mercaptopurine were more resistant to Klebsiella than were control mice.

Animals↗
PubMed1976

Failure of endotoxin to increase nonspecific resistance to infection of lipopolysaccharide low-responder mice.

In vitro and in vivo responses to lipopolysaccharide (LPS) and various other bacterial immunostimulants were compared in c3H/He low-responder mice. The principal findings were as follows. (i) Their splenic lymphocytes were stimulated by various gram-negative mitogens such as an Escherichia coli peptidoglycan, a detoxified derivative of LPS, and even endotoxins extracted by trichloroacetic acid that are known to contain protein; spleen cells of these mice were also transformed by two other B-cell mitogens extracted from acid-fast organisms. (ii) Their macrophages were refractory to LPS and weakly responsive to a mycobacterial prepartion. (iii) LPS failed to elicit nonspecific resistance in these mice against Klebsiella pneumoniae infection. (iv) Endotoxin extracted by trichloroacetic acid and a mycobacterial preparation that could increase nonspecific resistance to infection in other strains did not protect C3H/He mice against a challenge by K. pneumoniae, although both prepartions could evoke nonspecific responses of B cells in this low-responder subline.

Animals↗
PubMed1975

Biological activities of endotoxins detoxified by alkylation.

It has been previously observed that lipopolysaccharides can be detoxified by alkylation and yet retain their adjuvant activity. Our present findings confirm these results and show, moreover, that these derivatives did not lose their capacity to protect mice against lethal irradiation and lost only partially their ability to interrupt pregnancy or to induce blast transformation of murine B-lymphocytes. However, in contrast with lipopolysaccharides, these alkylated preparations did not enhance the nonspecific resistance of mice to a bacterial infection. The various bilogical functions of endotoxins can therefore be separated and are not uniformly related to their toxicity.

Abortion, Spontaneous↗
PubMed1975

[Protective effects of bacterial immunostimulants in mice infected by "Klebsiella pneumoniae" resistant to antibiotics after mutation or by plasmid transfer].

A streptomycin-resistant strain of K. pneumoniae obtained after mutation in vitro was found to be less virulent than the sensitive strain in mice. However, a single injection of lipopolysaccharides (LPS) administered 24 hours before challenge increased the host's resistance to both strains. In contrast, the virulence was not changed in K. pneumoniae accepting R-factors for ampicillin, streptomycin, chloramphenicol, tetracycline and sulphonamide. The plasmids were transferred to K. pneumoniae from two strains of Escherichia coli possessing different R-factors with the same resistance pattern. As in the first case, mice pretreated by endotoxin were protected against a challenge by microorganisms carrying R-factors. The capacity of the stimulated host to destory resistant or sensitive organisms was of the same order. Klebsiella recovered 5 or 24 hours after infection from the blood, liver and spleen did not lost their antibiotic-resistance. In this study, BCG and Corynebacterium granulosum were also used. Like LPS, these two immunostimulants protected very effectively mice infected with K. pneumoniae rendered resistant to antibiotics by R-factor transfer.

Ampicillin↗
PubMed1973

Preparation and biological properties of water-soluble adjuvant fractions from delipidated cells of Mycobacterium smegmatis and Nocardia opaca.

Digestion by lysozyme of delipidated cells of Mycobacterium smegmatis liberates a water-soluble immunoadjuvant fraction which is chemically very similar to the water-soluble adjuvant (WSA) obtained previously from purified cell walls, but which contains somewhat more non-peptidoglycan amino acids. The yield of peptidoglycan-arabinogalactan complex is about 10 times greater starting from whole cells than from cell walls. The main biological properties of this "neo-WSA" are described: it increases circulating antibodies to ovalbumin in guinea pigs, it does not produce polyarthritis in rats or induce hypersensitivity to tuberculin, it does not increase susceptibility to histamine or hyperreactivity to endotoxin, and does not produce spleen and liver hypertrophy. Analogous immunostimulant fractions have also been obtained from delipidated cells of Nocardia opaca by lysozyme treatment.

Adjuvants, Immunologic↗
PubMed1972

Biological study of a nontoxic, water-soluble immunoadjuvant from mycobacterial cell walls.

Whole mycobacterial cells, which are used in Freund's complete adjuvant, besides inducing hypersensitivity to tuberculoprotein, also can elicit hyperreactivity to endotoxins, lymphoid hyperplasia, and allergic polyarthritis in rats. The data reported here demonstrate that a potent water-soluble adjuvant obtained from mycobacterial cell walls is also effective in increasing the immune response to viruses, and that it is free of the toxic effects observed with whole mycobacterial cells.

Adjuvants, Immunologic↗