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R Laub

Publications and source records attributed to R Laub.

35 records · Page 2Linked to original sources

Antibiotic susceptibility of Salmonella spp. at different pH values.

We have examined the effects of acidic pH, in the range of those prevailing within phagosomes and lysosomes, on the growth and the susceptibility to different antibiotics of several strains of Salmonella spp. The minimal inhibitory concentration and the minimal bactericidal concentration of several beta-lactams were increased considerably during culture at pH 5.2. The extent of the increase was a function of: (1) the beta-lactam structure and, more particularly, the hydrophobicity of the side-chain of the molecule; and (2) the bacterial serotype. This phenotypic resistance at acid pH was not due to beta-lactamase activity or to a lower growth rate. In contrast, rifamycin SV was more active at acidic pH than at neutral pH and chloramphenicol, another highly hydrophobic drug, was equally efficacious at both pH values. Membrane lipopolysaccharide mutants, but not porin mutants, cultivated at an acidic pH were inhibited by lower concentrations of the beta-lactams. This suggests that the increased resistance to beta-lactams, and the increased susceptibility to rifamycin SV, at acidic pH, could have resulted from modified permeability of the outer membrane to antibiotics.

Anti-Bacterial Agents↗

[Demonstration of epidermal Langerhans cells].

Langerhans Cells (LC) are centrally involved in the induction of skin-located immunological processes, including kontactallergical reactions. Because of the growing interest in LC functions, and dynamics, various possibilities for their detection reaching from histological staining up to immunohistochemical characterization by means of monoclonal antibodies, have been developed. The concern of this paper is to overview different visualization techniques.

Dermatitis, Contact↗

Cellular pharmacology of deferrioxamine B and derivatives in cultured rat hepatocytes in relation to iron mobilization.

Two radiolabelled derivatives of deferrioxamine B (DF) have been synthesized: methyl-DF and acetyl-DF. Both derivatives are non cytotoxic and stable in cell culture but they are degraded in human plasma and more extensively in rat plasma. Methyl-DF, acetyl-DF and DF mobilize radioiron to the same extent from hepatocytes loaded with 59Fe citrate in the same range of extracellular concentrations. The uptake and release of the 3H-labelled derivatives and their corresponding iron complexes have been measured and appear to represent a passive phenomenon resulting from the gradient of concentration between the cellular compartment and the extracellular medium. The results indicate that only a limited pool of cellular iron is accessible for chelation and that neither the permeability of the cellular membrane, nor the intracellular concentration of the chelators are the limiting factors for iron mobilization. On the basis of the subcellular distribution of the 3H-DF analogues, methylamine inhibition of iron chelation by siderophores in cell cultures and the positive effect of acidic pH and hydrolysis by lysosomal enzymes on in vitro iron mobilization from radiolabelled ferritin, we suggest that iron mobilization by DF and its derivatives occurs in lysosomes where they complex iron released from ferritin under the conjugate actions of acidic pH and lysosomal enzymes.

Animals↗

Degradation of collagen and proteoglycan by macrophages and fibroblasts. Individual potentialities of each cell type and cooperative effects through the activation of fibroblasts by macrophages.

Fibroblasts and macrophages of various sources (peritoneal, alveolar or bone marrow-derived), from either rabbit or mouse, were cultured, independently or together, at the surface of [3H]proteoglycan/[14C]collagen-coated plates to evaluate their capacities for proteoglycan and collagen degradation. The various macrophage populations differed widely in their potentialities for proteoglycan and particularly, for collagen degradation, native collagen being significantly degraded, in this model only by rabbit alveolar macrophages. Fibroblasts were as active in proteoglycan degradation as the most active macrophage preparations, but their potential for collagen degradation appeared much higher than that of macrophages. Moreover, all types of macrophages secreted a factor, a monokine, that activated collagen and proteoglycan degradation by fibroblasts. Thus, fibroblasts might well be a major effector cell, active in connective tissue degradations occurring under chronic inflammatory situations.

Animals↗

Immunological relatedness of ribosomes from mycobacteria, nocardiae and corynebacteria, and microorganisms in leprosy lesions.

Serological relatedness of ribosomes from microorganisms of the Mycobacterium, Nocardia, and Corynebacterium genera has been analyzed by the microplate immunodiffusion technique. Mycobacterium and Nocardia proved homogeneous and closely related taxa, whereas Corynebacterium was found to be a heterogeneous phylum connected by remote links to the others. The taxonomic position of "diphtheroid microorganisms" (non-acid-fast, gram-positive bacteria morphologically similar to corynebactria), which were found together with Mycobacterium leprae in human leprosy lesions, was also investigated. Ribosomes of diphtheroid bacteria strongly cross-reacted with antisera against several mycobacteria and nocardiae but not against corynebacteria. Moreover, ribosomes from independently isolated diphtheroid strains proved serologically related and yielded strong cross-reactions with antisera against M. leprae as well as with sera from leprosy patients. Hence, diphtheroid microorganisms represent a homogeneous group immunologically related to mycobacteria in general and more specifically to M. leprae.

Corynebacterium↗

Mapping of natural anti-factor VIII antibodies in plasma pools from healthy donors: use of rationally designed synthetic peptides.

Inhibitor antibodies of blood coagulation factor VIII (FVIII) impair FVIII replacement therapy, constituting a serious complication in haemophilic patients. anti-FVIII antibodies may also develop in a variety of disease-associated autoimmunity. Mapping of human FVIII inhibitors in haemophilia A or autoantibody origin have delineated three major clusters of B-cell inhibitory epitopes (domain A2, A3 and C2). Inhibitory and non-inhibitory FVIII antibodies have also been described in plasma of healthy donors and pools of immunoglobulins. The purpose of this study was to use synthetic FVIII-peptides to more closely define regions of the molecule targeted by natural anti-FVIII antibodies. Predictive algorithms were used for defining the positions of potential continuous epitopes. To investigate the presence of peptide-reactive antibodies in normal plasma pools of healthy donors, a plasma fraction (Cohn fraction II+III) containing all IgG subclasses was purified by affinity chromatography on peptide-Sepharose columns. The results of ELISAs and Western blotting experiments (with the selected peptides and well-defined recombinant FVIII thrombin fragments) confirmed the reaction specificities of the affinity-purified human antibodies. For each IgG preparation, the isotopic subclass was also determined. In the clotting assay, several IgG preparations showed neutralising activity in a dose-dependent manner. Our observations support the recent hypothesis that FVIII inhibitors in haemophilia A and autoimmune disease may originate from the proliferation of natural FVIII-specific B-cell clones.

Autoantibodies↗