PubMed Health⌕ Search

Biomedical subjects

C Benezra

Publications and source records attributed to C Benezra.

At least 19 recordsLinked to original sources
PubMed1994

Optimization of the mouse ear swelling test for in vivo and in vitro studies of weak contact sensitizers.

Murine models for the assessment of the contact sensitizing properties of chemicals rely on mouse ear swelling tests (Mest), which are not sensitive enough to detect weak sensitizers. The aim of the present study was to develop in mice an adjuvant-free Mest appropriate for in vivo detection of any type of sensitizer (weak to strong), and useful for in vitro assessment of contact sensitivity (CS). 3 haptens were tested: dinitrochlorobenzene (DNCB), para-phenylenediamine (pPD) and isoeugenol. We compared various protocols for induction of the CS reaction, differing by the site of induction, the number of applications and the concentrations of the 3 haptens. Comparison of the induction site for optimal CS reaction showed that, in Balb/c mice, the back was a better site of induction than the abdomen. Detection of the sensitizing properties of weak sensitizers (pPD, isoeugenol) was possible using an adjuvant-free protocol, provided that the induction phase comprised hapten applications on 3 consecutive days on the backs of animals. For DNCB, one application was sufficient to obtain optimal CS reaction. For all 3 haptens, a secondary response in vitro was obtained using semi-purified lymph node T cells from animals sensitized 5 days before with the optimized Mest. These results demonstrate that the Mest could be a useful experimental model for the study of all types of contact sensitizers.

Animals↗
PubMed1993

Synthesis and interaction studies of 13C labeled lactone derivatives with a model protein using 13C NMR.

Two molecules 9 and 14, representatives of two series of electrophilic lactone derivatives, have been synthesized, and labeled with carbon 13 at their reactive sites. The mechanism and the products of the reaction of these two molecules with human serum albumin (HSA) under various reaction conditions have been studied by 13C NMR using DEPT 135 sequences. Results using the protein dissolved in aqueous medium or butylamine (a model nucleophile) dissolved in organic solvent were very similar. These results are entirely consistent with the in vivo allergising activity of these molecules. The validity of the Relative Alkylation Index (RAI) as a predicative model in contact allergy is discussed.

Alkylation↗
PubMed1993

Quantitative structure-activity relationships for skin sensitization potential of urushiol analogues.

The relative alkylation index (RAI), a theoretically derived parameter intended to quantify the relative extent of carrier haptenation resulting from a given dose of a given sensitizer, has previously been successfully applied to the analysis of relative sensitization potential and dose-response data for a variety of contact allergens which are directly electrophilic. Here the RAI concept is applied to analysis of data on compounds related to urushiol (i.e., 3-substituted catechols), the naturally occurring mixture of allergens responsible for contact allergy to poison ivy and poison oak. These allergens are believed to act as pro-electrophiles, being oxidized to electrophilic orthoquinones in vivo. It is found that the various types of urushiol derivatives fit the same sort of RAI-sensitization relationships as expected theoretically and as found previously with direct acting electrophiles. There is evidence that in many cases, the test conditions were such that overload effects, whereby the degree of sensitization induced decreases with increasing carrier haptenation, applied. It is also concluded that the question as to the relative sensitization potencies of the naturally occurring urushiols remains open. The commonly held view that with these materials, sensitization potential increases with increasing unsaturation in the 3-hydrocarbyl chain of the 3-hydrocarbyl catechols, is based on evidence that is capable of alternative interpretation.

Alkylation↗
PubMed1992

A murine in vitro model of allergic contact dermatitis to sesquiterpene alpha-methylene-gamma-butyrolactones.

The use of a lymphocyte transformation test (LTT) to provide evidence of allergic contact dermatitis was investigated. The haptens studied were alantolactone and isoalantolactone, two moderate allergens from Inula helenium L., a decorative and medicinal plant. Only alantolactone showed a significant response in vivo and in vitro in mice sensitized epicutaneously, without using Freund's complete adjuvant. Isoalantolactone did not show any sensitizing capacity in the murine model studied. The comparison of in vitro lymphocyte proliferation and in vivo allergenic capacity showed a good correlation and clearly demonstrates that, of the two sesquiterpene lactones, alantolactone is the better sensitizer.

Animals↗
PubMed1991

Allergic contact dermatitis caused by naturally occurring quinones.

Quinones play a major role in allergic contact dermatitis caused by plants. The principal allergens are benzoquinones or naphthoquinones but also compounds, such as catechols and other phenolic or flavonoid compounds, which are bioconverted into ortho-quinones or para-quinones. The high electrophilic reactivity of these compounds toward nucleophilic residues of proteins associated with lipophilic properties may explain that they are strong sensitizers. The more important allergens are reported and their structure-activity relationship is discussed.

Animals↗
PubMed1991

Refinement of the relative alkylation index (RAI) model for skin sensitization and application to mouse and guinea-pig test data for alkyl alkanesulphonates.

A derivation, more rigorous than hitherto, of the Relative Alkylation Index (RAI) as a quantifier of carrier protein haptenation in skin sensitization tests is presented. It is shown that the RAI, which is a composite parameter made up of dose, reactivity and lipophilicity terms, is likely to require a higher weighting for the reactivity term in the case of non-adjuvant tests than in the case of Freund's adjuvant-based tests. Methyl alkane-sulphonates, RSO3Me with R ranging from n-C6H13 to n-C16H33, were found to be skin sensitizers in a mouse ear swelling test, in agreement with published findings in a guinea-pig adjuvant model. A structure-activity relationship consistent with the published RAI model was observed whereby, in tests at fixed molar induction (0.1 mM) and challenge concentrations (0.025 mM), the level of sensitization response at first increased with increasing chain length of R, then showed a reversal of this trend at the highest chain length (R = n-C16H33). That this is a genuine 'over-load effect', as reported for several other series of compounds examined in guinea-pig adjuvant models, is indicated by the finding that on reducing the induction concentration for the R = n-C16H33 compound the sensitization response was increased. Alkyl and alkenyl methane-sulphonates, MeSO3R (R = n-C12H25, n-C18H37 and R = oleyl) did not give significant sensitization in the mouse ear test. Although they are chemically less reactive than methyl alkanesulphonates, these compounds are reported to be strong sensitizers in guinea-pig adjuvant tests and to fit a common quantitative sensitization-structure-dose relationship with the methyl alkanesulphonates.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkanesulfonates↗
PubMed1991

Perfluorinated analogues of poison ivy allergens. Synthesis and skin tolerogenic activity in mice.

3-(Tridecafluoroundecyl)catechol (8) and 3-(nonafluoropentadecyl)catechol (9), perfluorinated analogues of pentadecylcatechol (PDC), a constituent of poison ivy, have been synthesized. These compounds were nonsensitizers in mice. Compounds 8 and 9, however, were elicitors of allergic contact dermatitis in PDC-sensitized animals. Moreover, compound 9 exhibited tolerogenic properties to sensitization by poison ivy allergens, i.e. mice pretreated with perfluorinated compounds could not be sensitized to PDC.

Allergens↗
PubMed1991

A successful murine model for contact sensitization to a sesquiterpene-alpha-methylene-gamma-butyrolactone: sensitization to alantolactone in four strains of mice.

Induction of allergic contact hypersensitivity to a sesquiterpene lactone, alantolactone, was studied in four strains of mice: C3H/He, DBA/2, Balb/b, and Balb/c. The last three were successfully sensitized. A significant dose/response was demonstrated in these species, as well as an experimental "overload effect" in Balb/c and Balb/b strains. Histologic studies confirmed the allergic nature of the reaction. From the overall results, alantolactone can be considered a moderate sensitizer in mouse as well as in guinea pig. This study shows that the murine model can be used for experimental contact sensitization with moderate allergens, without the use of Freund's adjuvant for induction.

Animals↗
PubMed1990

Sensitizing capacity of three methyl alkanesulphonates: a murine in vivo and in vitro model of allergic contact dermatitis.

A murine model for in vivo and in vitro studies of contact sensitization to methyl alkanesulphonate derivatives has been developed. Contact sensitivity was quantified in vivo by measuring the ear thickness increase, and the influence of the alkyl chain length (hexyl, dodecyl, hexadecyl) was investigated. Long chain methyl alkanesulphonates (dodecyl and hexadecyl) are strong sensitizers, while the shorter alkyl chain, methyl hexanesulphonate, is a weak sensitizer. In vitro lymphocyte blastogenesis was measured by the 3H-thymidine uptake and exhibited a stimulation index between 2 and 8. The results nicely parallelled the in vivo sensitization measurements, except for methyl dodecanesulphonate. This could be explained by the cytotoxic activity of this compound, the most toxic of the three methyl alkanesulphonates tested. Thus, murine sensitization to methyl alkanesulphonates provides a good model system for preliminary investigations of delayed type hypersensitivity mechanisms.

Alkanesulfonates↗
PubMed1990

Cross-reaction in allergic contact dermatitis from alpha-methylene-gamma-butyrolactones: importance of the cis or trans ring junction.

Cross-reaction in allergic contact dermatitis (ACD) is a highly stereoselective process. The importance of the cis or trans ring junction in alpha-methylene-gamma-butyrolactones in cross-reactivity was investigated by reacting Helenin (mostly a mixture of natural allergenic sesquiterpene lactones alantolactone 1 and isoalantolactone 2, which present a cis ring junction) in guinea pigs sensitized to model allergenic alpha-methylene-gamma-butyrolactones: cis-bicyclic lactone 3 and trans-bicyclic lactone 4.

Animals↗
PubMed1990

Patch testing with the "sesquiterpene lactone mix": a marker for contact allergy to Compositae and other sesquiterpene-lactone-containing plants. A multicentre study of the EECDRG.

6278 patients were patch tested with a sesquiterpene lactone mix (SL-mix) in 10 European clinics. 4011 patients were tested only with 0.1% SL-mix, 63 (approximately 1.5%) of whom were positive, with 26 (41%) of these cases being considered clinically relevant. There were no cases of active sensitization, though 5 cases of irritation were reported. 22 irritant reactions and 22 cases of active sensitization occurred when testing also with 1% and 0.33% concentrations of SL-mix. SL-mix 0.1% pet. is shown to be an important patch test and many relevant sensitizations will be missed without routine screening with such a mix. Most patients with SL-mix sensitivity presented with hand and/or face dermatitis, apparent photodermatitis or more generalised eczema.

Dermatitis, Contact↗
PubMed1989

Allergic contact dermatitis to Ginkgo biloba L.: relationship with urushiol.

A Ginkgo biloba L. fruit extract was prepared and purified. Three groups of guinea pigs were sensitized to the crude extract, anacardic acids 1, and cardanols 2 respectively, using the FCAT method, and the fourth group to urushiol using the epicutaneous route. Each group was tested for reaction to the primary sensitizer and to the different main aromatic compounds isolated from Ginkgo fruits. Anacardic acids were found to be good sensitizers, while cardanols failed to induce allergic contact dermatitis (ACD). No cross-reactions were observed among the compounds tested. Ginkgolic acids 1 seem to be the main allergens of Ginkgo biloba L. and the hypothesis of a biotransformation of 1 into catechol 4 is not supported by experiment.

Animals↗
PubMed1989

ATPase and morphologic changes in Langerhans cells induced by epicutaneous application of a sensitizing dose of DNFB.

We have previously described an ATPase Langerhans cell (LC) staining technique allowing progression from light to electron microscope observation. Using this technique we have studied, following epicutaneous application of a sensitizing dose of a hapten, 2,4-dinitro-1-fluorobenzene (DNFB), the fate of the epidermal LC located in the sensitization zone. We wanted to know, under the light microscope, if the density and/or morphology of the LC are modified by such a treatment and, under the electron microscope, what are the ultrastructural changes accompanying the possible light microscope modifications. Under the light microscope, the observation of LC during the 5 d necessary for the development of contact sensitivity to DNFB shows that their number drops in the course of the first 24 h to normalize again 3 d later. Under the electron microscope, observations over the first 24 h revealed that LC remained in the epidermis, but were ATPase-negative. The disappearance of the membrane ATPase activity took place while the LC presented an increased number of coated pits, coated vesicles, endosomes, and lysosome organelles which characterize, at the ultrastructural level, the process of receptor-mediated endocytosis (RME). Following RME, many Birbeck granules (BG) appeared in the cytoplasm. Thus, epicutaneous application of DNFB leads to an endocytic activation of LC. However, the ligand(s) and/or the cell-surface components, which probably internalize during the RME process, remain unknown.

Adenosine Triphosphatases↗
PubMed1988

Allergic contact dermatitis to tulips: an example of enantiospecificity.

Allergic contact dermatitis (ACD), an immunological reaction of the skin resulting from contact with reactive compounds occurring in plants was shown to the enantiospecific (animals sensitized to a compound do not react to its nonsuperimposable mirror image). Thus, when guinea pigs were experimentally sensitized to (+)-tulipalin B (a compound present in tulip bulbs) they did not react to its enantiomer, (-)-tulipalin B. This was also true for (+)- and (-)-beta-hydroxy-gamma-methyl-alpha-methylene-gamma-butyrolactones.

4-Butyrolactone↗
PubMed1987

Double-headed haptens with pyrocatechol (poison ivy like) and methylene lactone functional groups: a search for skin-tolerance inducers.

In order to develop new theories for desensitization, a potential skin sensitizer, 1, with two different haptenic ends, a pyrocatechol group and an alpha-methylene-gamma-butyrolactone moiety, separated by a straight nine-carbon-atom chain has been prepared and used to sensitize guinea pigs. A "monohapten" 8 containing an electrophylic alpha-methylene-gamma-butyrolactone, connected to a dimethoxybenzene group, has also been prepared. Both the "bihapten" 1 and the "monohapten" 8 were shown to be sensitizers. Bihapten 1 sensitized animals recognized only bihapten 1 (and not the lactone 8) while monohapten 8 sensitized guinea pigs reacted to both 8 and 1. Bihapten 1 treated animals were further sensitized to monohapten 8 and challenged to the latter: the skin intensity reaction was significantly lower than the test to 8 in 8-sensitized animals. Bihapten 1 seems therefore to "tolerize" against the alpha-methylene-gamma-butyrolactone end.

Animals↗