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Biomedical subjects

C Benezra

Publications and source records attributed to C Benezra.

At least 37 records · Page 2Linked to original sources
PubMed1987

Stereospecificity in allergic contact dermatitis to simple substituted methylene lactone derivatives.

The enantiomers of beta,gamma-dimethyl- and beta-methyl-alpha-methylene-gamma-butyrolactones have been synthesized stereospecifically from glutamic acid and beta-hydroxy isobutyric acid, respectively. Guinea pigs have been sensitized (Freund complete adjuvant technique) and tested to them. Both enantiomers of beta-methyl lactone as well as (+)-beta,gamma-dimethyl lactone induced enantiospecific allergic contact dermatitis (ACD); in turn, (-)-beta,gamma-dimethyl lactone showed no specificity. An interpretation is proposed.

4-Butyrolactone↗
PubMed1987

Human epidermal Langerhans cells internalize by receptor-mediated endocytosis T6 (CD1 "NA1/34") surface antigen. Birbeck granules are involved in the intracellular traffic of the T6 antigen.

Using immunogold staining of a suspension of living human epidermal cells to identify the Langerhans cell membrane-associated antigen T6 (revealed by the monoclonal antibody BL6), we have observed internalization of T6 antigen in Langerhans cells. This phenomenon is at least partly due to receptor-mediated endocytosis involving coated pits, coated vesicles, endosomes, the smooth endoplasmic reticulum, and lysosomes. These ultrastructural results suggest that T6 antigen may be part of a receptor site. Following receptor-mediated endocytosis, the appearance in the cell center of the first labeled Birbeck granules suggests that Birbeck granules could represent T6 intracellular transport organelles carrying T6 from the central part of the cell to an unknown destination.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Contact dermatitis. A review.

In recent years, there has been a dramatic rise in our understanding of contact dermatitis. This paper is a review of our knowledge of the mechanisms involved in contact dermatitis and related phenomena, the investigation of these events and the emergence of significant new allergens during the last 5 years.

Allergens↗
PubMed1986

Saturated analogues of poison ivy allergens. Synthesis of trans,trans- and cis,trans-3-alkyl-1,2-cyclohexanediols and sensitizing properties in allergic contact dermatitis.

Saturated analogues of poison ivy and oak allergens (3-alkylcatechols), i.e. trans,trans-3-alkyl-1,2-cyclohexanediols (alkyl = CH3, n-C5H11, n-C10H21, n-C15H31), have been prepared and used to sensitize guinea pigs. Only long-chain derivatives (carbon chain length greater than C10) are contact sensitizers. The sensitized animals cross-react to PDC (i.e. pentadecylcatechol, one of the allergens of poison ivy), but the converse is not true (PDC-sensitized animals do not react to cyclohexanediols). cis,trans-3-n-Pentadecyl-1,2-cyclohexanediol has also been synthesized and shown to be a sensitizer. There is not cross-reaction between trans,trans- and cis,trans-3-n-pentadecylcyclohexanediols, excluding a common skin metabolite.

Allergens↗
PubMed1986

Allergenic alpha-methylene-gamma-butyrolactones. Study of the capacity of beta-acetoxy- and beta-hydroxy-alpha-methylene-gamma-butyrolactones to induce allergic contact dermatitis in guinea pigs.

(+/-)-Tulipalin B was prepared in six steps from phenyl sulfide and ethyl 2-bromopropionate. The sensitizing power in the skin of (+/-)-tulipalin A (1a) and B (1b) and of the beta-acetoxy derivatives (1c) was studied. All are able to induce allergic contact dermatitis (ACD) and give cross-reactions. gamma,gamma-Disubstituted analogues (with a -(CH2)5- chain in the gamma-position) were synthesized and used to induce ACD in guinea pigs: they all were sensitizers and cross-reacted. However no cross-reaction was demonstrated between gamma,gamma-unsubstituted and gamma,gamma-substituted compounds showing a great specificity of ACD.

4-Butyrolactone↗
PubMed1986

ATPase Langerhans cell staining: a technique allowing progression from light to electron microscope observation.

A technique which enables good visualization of the membranous ATPase activity of epidermal Langerhans cells is described. The method has the advantage of keeping intact most of the ultrastructural details. It may allow the observation, under pathologic conditions, of ultrastructural modifications in ATPase-negative Langerhans cells still recognizable by their Langerhans cell granules.

Adenosine Triphosphatases↗
PubMed1986

Induction of tolerance to poison ivy urushiol in the guinea pig by epicutaneous application of the structural analog 5-methyl-3-n-pentadecylcatechol.

Previous studies have established that epicutaneous application of 5-methyl-3-n-pentadecylcatechol (5-Me-PDC), a synthetic analog of a poison ivy urushiol component, leads to immune tolerance to 3-n-pentadecylcatechol (PDC) in mice. The induction of tolerance by 5-Me-PDC may be mediated by a protein conjugate formed via selective reaction of thiol nucleophiles present on the carrier macromolecule with the corresponding o-quinone derived from the parent catechol. In order to examine further the tolerogenic properties of 5-Me-PDC, we have extended our studies to the guinea pig, the generally accepted experimental species for the study of contact allergy. The results have established that specific immune tolerance to poison ivy urushiol is induced following 2 epicutaneous applications of the PDC analog. Furthermore, we were able to show that the treated animals remained tolerant for at least 6 weeks, a period of time comparable to that observed following the intravenous administration of the O,O-bis-acetyl derivative of PDC. The data point to the possibility of developing a therapeutically effective topical tolerogen for poison ivy contact dermatitis.

Administration, Topical↗
PubMed1986

Molecular recognition patterns of sesquiterpene lactones in costus-sensitive patients.

A molecular analysis of cross-reactions in costus-sensitive patients reveals that the most active sesquiterpene lactones are the ones with the lesser number of oxygenated substituents close to the alpha-methylene-gamma-butyrolactone ring. Cross-reactions with sesquiterpene lactones with different skeletons (germacranolide and guaianolide or pseudoguaianolide lactones) can probably be explained by concomitant multiple sensitization to two lactones present in costus, respectively costunolide and dehydrocostus lactone.

Dermatitis, Contact↗
PubMed1985

Induction of tolerance to urushiol by epicutaneous application of this hapten on dinitrofluorobenzene-treated skin.

The application of a sensitizing dose of urushiol on a dinitrofluorobenzene (DNFB)-treated skin area significantly diminished the intensity of the urushiol challenge test in guinea pigs. Furthermore, the animals which had been first exposed to urushiol through DNFB-treated skin failed to become sensitized in a second sensitization attempt even when painted on a previously untreated area. This tolerance is hapten-specific and may be reversed by treatment with cyclophosphamide (200 mg/kg) shortly before another contact sensitization attempt to urushiol. In a previous work, we have shown that most of the Langerhans cells present in the DNFB-treated skin area are ATPase-negative and that there exists a link between the membranous ATPase system and the formation of Langerhans cell granules. The latter seem to develop in the course of a mechanism of adsorptive pinocytosis during which ATPase activity "disappears." Thus we suggest that the "unavailability" of ATPase-negative Langerhans cells for adequate processing a second hapten may result from the incapacity of cells lacking their ATPase system to activate the intracellular events that depend on this system and that normally lead to sensitization.

Adenosine Triphosphatases↗
PubMed1985

ATPase and morphologic changes induced by UVB on Langerhans cells in guinea pigs.

We have devised, in guinea pigs, an improved ATPase technique which enables one to proceed from light to electron microscope study while preserving, on the ultrastructural level, the various membranous structures, in particular the Langerhans cell (LC) granules. Using this method, we have been able to confirm the action of acute, low-dose UVB on the surface enzymatic marker, ATPase. Moreover, this study has shown that the ATPase-negative LC contain abnormal LC granules or, more often, are deficient in LC granules. In a previous work, we have shown that, after epicutaneous application of a hapten, one successively observes an extensive adsorptive pinocytosis process, the disappearance of the membranous ATPase system, and the appearance of LC granules in the cytoplasm. Therefore we may suppose that, after UVB irradiation, the disappearance of the ATPase system and/or the possible alteration of the adsorptive pinocytosis process interrupts or alters the formation of LC granules. These successive events might play a vital role in the formation of the hapten--carrier protein-Ia antigen complex. In their absence in a large number of LC, following UV irradiation, epicutaneous application of a hapten would lead to the development of a state of immune tolerance.

Adenosine Triphosphatases↗
PubMed1985

A systematic search for structure-activity relationships of skin contact sensitizers: methodology.

A computerized resource for the systematic evaluation of the structure-activity relationships and other aspects of contact allergens is described. This resource consists of a data base of results of contact dermatitis tests and a structural classification scheme for contact allergens that is called a Structure-Activity (S/A) Tree. The data base now contains approximately 2200 test results extracted from the journal Contact Dermatitis (1975-1982) and is continually being expanded. The S/A Tree is being developed to provide an index to structure-activity relationships of contact allergens; 63 structural groups are currently indexed. Analyses of benzoquinones and gallic acid esters are presented as examples of the potential application of this resource to such problems as the identification of potential cross-reactants, appropriate test concentrations and vehicles, and the reliability of available test results.

Animals↗
PubMed1985

[Formation of Langerhans granules seems linked to membrane ATPase activity of epidermal Langerhans cells].

The epidermis contains a population of dendritic cells, Langerhans cells (LC), derived from cells originating from bone marrow, bearing receptors for the Fc fragment of IgG and for the C3 fraction of complement and expressing at their surface Ia antigens of the major histocompatibility system. These cells with multiple immunological functions are capable of presenting antigens to immunocompetent cells. The labeling of LC through revelation of their membranous ATPase activity constitutes one of the best available techniques for their visualization. Moreover, the presence of this ATPase activity appears to be a prerequisite for the induction of contact sensitivity, since in the absence of such activity, the epicutaneous application of a hapten induces a state of immunological tolerance. Applying, at a sensitizing dose, 2,4-dinitrofluorobenzene (DNFB) on an untreated guinea-pig skin surface results in a momentary drop in the number of ATPase positive LC in the application zone. Using an improved technique for ATPase labeling (Hanau et coll. submitted for publication, 1985)--which allows one to extend the study from optical to electron microscopy--we observed by electron microscopy the formation, within the LC, of numerous Langerhans granules, concurrent with the loss of ATPase membranous activity. These granules, first described by Birbeck et coll. and specific to LC in the epidermis, have a complex structure. On a section, they may display either a linear aspect (rod-like)--with sometimes a vesicular portion at one extremity (racket-like)--or a circular shape. Whatever their shape, they always show a central striation, which gives them a zipper-like appearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1984

Allergic contact dermatitis to laurel (Laurus nobilis L.): isolation and identification of haptens.

Two methods, using methylenelactone dimethylamino adducts, were used to remove selectively alpha-methylene gamma-butyrolactones from Laurus nobilis L. extracts. Isolated lactones were identified and "treated" extracts recovered. Two guinea-pig groups were sensitized to crude extracts and "treated" extracts, respectively, and tested with primary sensitizer and with different lactones. Only the first group showed strong skin reactions to crude extracts and to the lactones. Treated extracts were shown to be anallergic.

4-Butyrolactone↗