A Novel Antigen-Sampling Cell in the Teleost Gill Epithelium With the Potential for Direct Antigen Presentation in Mucosal Tissue.

In mammals, M cells can take up antigens through mucosal surfaces of the gut and the respiratory tract. Since M cells are deficient of lysosomes and phagosomes, the antigens are directly delivered to the mucosa-associated lymphoid tissue (MALT) without degradation. In teleost fish, the entire body surface (gills, skin, and intestinal system) is covered by mucus; however, specific antigen-sampling cells have not yet been identified in their mucosal tissues. Here, we show that two phenotypes of antigen-sampling cells take up antigens through epithelial surfaces of the rainbow trout gill. One phenotype of antigen-sampling cells has features of monocyte/macrophage/dendritic cell-type cells; they have large vacuoles in the cytoplasm and express PTPRC (CD45), CD83, IL-1ß, and IL-12p40b. The second phenotype exhibits similar characteristics to mammalian M cells; the corresponding cells bind the lectin UEA-1 but not WGA and show expression of M cell marker gene Anxa5. In contrast to mammalian M cells, teleost M-type cells were found to exhibit small vacuoles in their cytoplasm and to express almost all genes related to the "phagosome", "lysosome," and "antigen processing and presentation" pathways. Furthermore, MHC class II was constitutively expressed on a fraction of M-type cells, and this expression was significantly increased after antigen uptake, suggesting that the MHC class II is inducible by antigen stimulation. Here, we suggest that teleost M-type cells play a role in the phylogenetically primitive teleost immune system, similar to bona-fide M cells. In addition, the presence of MHC class II expression suggests an additional role in antigen presentation in the gills, which are an organ with high T cell abundance, especially in interbranchial lymphoid tissue. The present results suggest an unconventional antigen presentation mechanism in the primitive mucosal immune system of teleosts, which generally lack highly organized lymphoid tissues. Moreover, the results of this work may be valuable for the development of mucosal vaccines that specifically target M-type cells; mucosal vaccines significantly reduce working costs and the stress that is usually induced by vaccination via injection of individual fish.

Dentomaxillofacial characteristics of ectodermal dysplasia.

The aim of this retrospective hospital-based study was to elucidate the dentomaxillofacial characteristics of ectodermal dysplasia. Six Japanese individuals (one male and five female; age range, 12.7-27.2 years) underwent comprehensive examinations, including history recording, cephalometric analysis, panoramic radiography, and analysis of dental models. All the subjects had two or more major manifestations for clinical diagnosis of ectodermal dysplasia (e.g., defects of hair, teeth, nails, and sweat glands). They presented hypodontia (mean number of missing teeth, 9.5; range, 5-14), especially in the premolar region, and enamel dysplasia. Five subjects had bilateral molar occlusion, whereas one subject had unilateral molar occlusion. The common skeletal features were small facial height, maxillary hypoplasia, counterclockwise rotation of the mandible, and mandibular protrusion. Interestingly, the maxillary first molars were located in higher positions and the upper anterior facial height was smaller than the Japanese norm. The results suggest that vertical and anteroposterior maxillary growth retardation, rather than lack of occlusal support due to hypodontia, leads to reduced anterior facial height in individuals with ectodermal dysplasia.

Simulation of the toxicokinetics of trichloroethylene, methylene chloride, styrene and n-hexane by a toxicokinetics/toxicodynamics model using experimental data.

The toxicokinetics/toxicodynamics (TKTD) model simulates the toxicokinetics of a chemical based on physiological data such as blood flow, tissue partition coefficients and metabolism. In this study, Andersen and Clewell's TKTD model was used with seven compartments and ten differential equations for calculating chemical balances in the compartments (Andersen and Clewell 1996, Workshop on physiologically-based pharmacokinetic/pharmacodynamic modeling and risk assessment, Aug. 5-16 at Colorado State University, U.S.A) . Using this model, the authors attempted to simulate the behavior of four chemicals: trichloroethylene, methylene chloride, styrene and n-hexane, and the results were evaluated. Simulations of the behavior of trichloroethylene taken in via inhalation and oral exposure routes were also done. The differences between simulations and measurements are due to the differences between the absorption rates of the exposure routes. By changing the absorption rates, the simulation showed agreement with the measured values. The simulations of the other three chemicals showed good results. Thus, this model is useful for simulating the behavior of chemicals for preliminary toxicity assessment.

Prediction of systemic concentrations of sensitizing compound using TKTD simulation model.

To investigate the safe handling of an industrial product, phenyl vinyl sulfone (PVS), which has an extremely high potential for dermal sensitization at low concentrations and positive mutagenicity, the maximum no-effect concentration for dermal deposits was obtained from dermal sensitization experiments. The systemic concentrations in the liver, which is considered to be a target tissue of mutation, were monitored using the TKTD (Toxico Kinetics Toxico Dynamics) model by inputting the maximum no-effect concentration of sensitization. The predicted highest concentration in the liver was compared with the no-effect level of mutation in the same tissue, which was derived from an in vitro mutagenicity study. The results showed that when this product is handled at lower concentrations, which may not induce dermal sensitization, the systemic concentrations would be lower than those causing mutation in the liver. In workplaces, conditions that prevent dermal sensitization caused by PVS could also protect against the mutagenicity of this compound.