Biomedical subjects

J Ezendam

Publications and source records attributed to J Ezendam.

4 recordsLinked to original sources

PubMed2003

Chemical-specific properties co-determine the type of adverse immune response.

Many drugs but also environmental pollutants may cause adverse reactions in susceptible individuals that are reminiscent of autoimmune syndromes. Apart from a number of predisposing often inherent, idiosyncratic determinants, chemical-specific properties might be involved as well. Notably, reactive chemicals or metabolites may provoke formation or release of immunosensitizing neo-antigens (a.o. hapten-carrier complexes or cryptic epitopes). In addition reactive chemicals but also certain inert chemicals may trigger macrophages and other inflammatory cells to release proinflammatory products that, via elicitation of costimulatory help, support hapten- or neo-antigen-specific T cell activation. In addition, chemicals may influence immunoregulatory processes and modulate for instance the balance between type 1 and type 2 responses. Here, we review data showing that chemically induced upregulation of second or costimulatory signals co-determines not only whether, but also what type of an adverse immune response (type 1 or type 2) is triggered.

Adjuvants, Immunologic↗

PubMed2002

Predictive testing for autoimmunity.

Many chemicals, in particular drugs, cause systemic allergy or autoimmune-like disorders. Due to complex pathogenesis and strong dependence on genetic make-up, these immunotoxicological effects are usually missed in standard toxicity testing. Besides, animal studies that demonstrate chemically induced systemic allergy or autoimmune-like disorders are scarce. Here, animal models are presented that would fit into a predictive two-tiered strategy, designed to allow screening for immunostimulatory potential in the first tier, and more elaborate testing for allergenic or autoimmunogenic potential of selected chemicals in the second tier. The popliteal lymph node assay (PLNA), with or without reporter antigens, would fit in the first tier, and relevant route of exposure protocols with selected strains of mice or rats may be further developed to compose the second tier. To date, the relevant route of exposure models mentioned here (with 'normal' inbred mice and/or Brown Norway rats) has been tested with only a few chemicals, and the PLNA, although tested with over 100 chemicals, is not validated as yet. Conceivably, a major challenge in immunotoxicology is to incorporate the present knowledge on chemical-induced systemic allergy and autoimmunity in further development and validation of predictive models and strategies.

Animals↗

PubMed2000

DR2 antigens are associated with severity of disease in toxic oil syndrome (TOS).

Toxic oil syndrome (TOS) was an epidemic which broke out in Spain in 1981, caused by the ingestion of rapeseed oil denatured with 2% aniline and sold illegally as edible oil. More than 20,000 people were affected and mortality rate was 8.4%. Genetic susceptibility appears to be involved in the pathology of this disease. Several reports have described association between the chronic stage of the disease and DR-DQ antigens (DR3, DR4, DR2 and DQ8). In the present work, we have reassessed the HLA class II antigens in a well-designed case-control study. Triplets of subjects (n=265) composed by chronic patients (n=117), non-affected family members (n=71) and non-related controls (n=77) were studied. Also, HLA class II antigens were analyzed in patients who had died from TOS (n= 34) and in TOS control patients who died from other non-TOS related causes (n=13). Regarding surviving patients no significant association was found between HLA and disease. In contrast, an increase in phenotypic frequency of DR2 antigen, was found in patients who had died from TOS (73.5%) compared with the whole study group: TOS-affected alive patients (25.6%, corrected P<0.001), non-affected family members (28.5%, corrected P<0.001), non-related controls (23.9%, corrected P<0.001) and dead controls (38.4%, P=0.03).

Aniline Compounds↗

PubMed1998

Epidermal cell kinetics by combining in situ hybridization and immunohistochemistry.

Double labelling can serve as a useful tool for providing information about cell kinetics in normal and hyperproliferative tissues in general, and skin in particular. We have developed a double-labelling method that combines immunohistochemistry using the monoclonal antibody MIB1 and non-isotopic in situ hybridization using either a digoxigenin-labelled RNA probe specific for histone 3 mRNA sequences or a Fluorescein-labelled oligonucleotide probe specific for histone 2b, 3, 4 mRNA sequences. Double labelling was performed on normal, tape-stripped normal skin and psoriatic skin. The three proliferation markers were also examined by single labelling. The ratio of cells in the S-phase (Ns) and the growth fraction (Ncy) was determined. In normal skin, psoriatic skin and tape-stripped normal skin after 24 h and after 48 h, we calculated that 15%, 16%, 3% and 12% of growth fraction consisted of cells in the S-phase respectively. The S-phase lasts approximately 10 h, so the cell cycle time in normal and psoriatic skin is approximately 62.5 h. At present, the MIB1/H3 digoxigenin or MIB1/H2b-H3-H4 Fluorescein double-labelling technique cannot be used routinely. Therefore, in order to understand the cell kinetic processes better, experiments are recommended to optimize these methods. From a practical point of view and for reasons of specificity and sensitivity, we prefer the Fluorescein-labelled oligonucleotide probe method.

Cell Division↗