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E Gleichmann

Publications and source records attributed to E Gleichmann.

119 records · Page 7Linked to original sources
PubMed1970

Chronic allogeneic disease. II. Development of lymphomas.

The incidence of lymphomas in 371 CAF(1) mice injected with BALB/c spleen cells was compared with that in 324 control CAF(1) mice. A high incidence of lymphomas was found in the treated mice, but not in the control animals. The development of the neoplasms was a function of the number of parental cells administered. Analyses of the injected mice for the presence of donor cells indicated that the majority of the injected parental cells lost antihost activity, probably within 24 hr of their administration. The tumors were of host origin, as judged by transplantation tests and antigenic analysis of tumor cells.

Animals↗
PubMedDate not supplied

T cell-dependent immune reactions to reactive benzene metabolites in mice.

Using the popliteal lymph node (PLN) assay in mice, we studied the sensitizing potential of benzene and its metabolites. Whereas benzene and phenol failed to induce a PLN reaction, catechol and hydroquinone induced a moderate, and p-benzoquinone a vigorous response. Following a single injection of the reactive metabolite p-benzoquinone (100 nmol/mouse), cellularity in the draining PLN was increased > 15-fold, and reverted back to normal only after approximately 100 days. Although the PLN response was T cell-dependent, flow cytometric analysis revealed that the increased cellularity in the PLN after a single injection of p-benzoquinone was mainly due to an increase in B cells. Mice primed to p-benzoquinone and challenged with a small dose of p-benzoquinone (0.1 nmol/mouse) mounted a secondary PLN reaction, indicating hapten specificity of the reaction; this was confirmed by results obtained in the adoptive transfer PLN assay. An unexpected finding was the secondary PLN response to benzene (1 nmol/mouse) observed in mice primed to p-benzoquinone. This finding suggests that some of the benzene (at least 10%) was locally converted into p-benzoquinone, which then elicited the secondary response observed. In conclusion, the reactive intermediate metabolites hydroquinone and p-benzoquinone can act as haptens and sensitize; their precursors, benzene and phenol, may be considered as prohaptens.

Animals↗
PubMedDate not supplied

Increased frequencies of cytochrome P4501A1 polymorphisms in infertile men.

Genetic factors that could mediate the pathogenesis of male reproductive disorders are largely unclear. Polymorphisms of cytochrome P4501A1 (CYP1A1), a key enzyme in the extrahepatic metabolism of lipophilic xenobiotics, have been shown to influence susceptibility to xenobiotics. Here, CYP1A1 polymorphisms were investigated in 134 infertile Caucasian men. The frequencies of the Mspl polymorphism in the 3'-flanking region of the CYP1A1 gene and a mutation in exon 7 causing an isoleucine-valine exchange (IVE) in the heme-binding region of the enzyme were increased among infertile men when compared with those of unselected, healthy male controls (odds ratio (OR)) 1.4, Cl95 0.68-2.89 for Mspl polymorphism; OR 2.4, Cl95 0.83-6.95 for IVE). Patients with normozoospermia revealed the highest frequencies for both polymorphisms (n = 8; OR 4.5, Cl95 0.97-20.91 for Mspl polymorphism; OR 13.7, Cl95 2.53-74.13 for IVE). ORs for the IVE exceeded the values calculated for the Mspl polymorphism. These preliminary results suggest that genetic variation in the metabolism of xenobiotics may codetermine individual susceptibility to infertility.

Cytochrome P-450 CYP1A1↗
PubMedDate not supplied

[Gold antirheumatic drug: desired and adverse effects of Au(I) and Au(III) [corrected] on the immune system.

Three new findings are reviewed that help to understand the mechanisms of action of anti-rheumatic gold drugs, such as disodium aurothiomalate (Na2Au(I)TM): i) We found that Na2Au(I)TM selectively inhibits T-cell receptor-mediated antigen recognition by murine CD4+ T-cell hybridomas specific for antigenic peptides containing at least two cysteine residues. Presumably, Au(I) acts as a chelating agent forming linear complexes (Cys-Au(I)-Cys) which prevents correct antigen-processing and/or peptide recognition by the T-cell receptor, ii) We were able to show that Au(I) is oxidized to Au(III) in mononuclear phagocytes, such as macrophages. Because Au(III) rapidly oxidizes protein and itself is re-reduced to Au(I), this may introduce an Au(I)/Au(III) redox system into phagocytes which scavenges reactive oxygen species, such as hypochlorous acid (HOCl) and inactivates lysosomal enzymes, iii) Pretreatment with Au(III) of a model protein antigen, bovine ribonuclease A (RNase A), induced novel antigenic determinants recognized by CD4+ T lymphocytes. Analysis of the fine specificity of these "Au(III)-specific" T-cells revealed that they react to RNase peptides that are not presented to T-cells when the native protein, i.e., not treated with Au(III), is used as antigen. The T-cell recognition of these cryptic peptides did not require the presence of gold. This finding has important implications for understanding the pathogenesis of allergic and autoimmune responses induced by gold drugs. Taken together, our findings indicate that Au(I) and Au(III) each exert specific effects on several distinct functions of macrophages and the activation of T-cells. These effects may explain both the desired anti-inflammatory and the adverse effects of antirheumatic gold drugs.

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