T cells participate in bone remodeling during the rapid palatal expansion.

Palatal expansion has been widely used for the treatment of transverse discrepancy or maxillae hypoplasia, but the biological mechanism of bone formation during this procedure is largely unknown. Osteoclasts, which could be regulated by T cells and other components of the immune system, play a crucial role in force-induced bone remodeling. However, whether T cells participate in the palatal expansion process remains to be determined. In this study, we conducted the tooth borne rapid palatal expansion model on the mouse, and detect whether the helper T cells (Th) and regulatory T cells (Treg) could affect osteoclasts and further bone formation. After bonding open spring palatal expanders for 3-day, 5-day, 7-day, and retention for 28-day, micro-computed tomography scanning, histologic, and immunofluorescence staining were conducted to evaluate how osteoclasts were regulated by T cells during the bone remodeling process. We revealed that the increased osteoclast number was downregulated at the end of the early stage of rapid palatal expansion. Type 1 helper T (Th1) cells and Type 17 helper T (Th17) cells increased initially and promoted osteoclastogenesis. Thereafter, the regulatory T (Treg) cells emerged and maintained a relatively high level at the late stage of the experiment to downregulate the osteoclast number by inhibiting Th1 and Th17 cells, which governed the new bone formation. In conclusion, orchestrated T cells are able to regulate osteoclasts at the early stage of rapid palatal expansion and further facilitate bone formation during retention. This study identifies that T cells participate in the palatal expansion procedure by regulating osteoclasts and implies the potential possibility for clinically modulating T cells to improve the palatal expansion efficacy.

[The histomorphological changes in the mucosa of the edges of the cleft palate and their effect on surgical wound healing]. / Gistomorfologicheskie izmeneniia slizistoi obolochki kraev nesrashcheniia neba i ikh vliianie na zazhivlenie operatsionnoi rany.

The study has involved 30 children aged 4 to 6 with cleft lip and palate. Histomorphologic changes of soft tissues on cleft palate edges were detected; these inflammatory dystrophic changes are associated with reduction of the body nonspecific reactivity.

Primary nodular lymphocyte predominant Hodgkin lymphoma of the palate: a rare incidence which was also associated with progressive transformation of germinal centres of cervical lymph node.

Primary manifestation of nodular lymphocyte predominant Hodgkin lymphoma in oral cavity is very rare. We are describing such a case which was associated with progressive transformation of germinal centres in a cervical lymph node.

Paracetamol-induced fixed drug eruption at an unusual site.

BACKGROUND: Paracetamol (acetaminophen) is a widely used analgesic/antipyretic drug for which hypersensitivity reactions appear to be increasingly frequent. OBJECTIVE: We report the case of a woman who experienced several delayed selective reactions induced by paracetamol: fixed drug eruptions (FDEs) with typical features but an unusual distribution (hard palate and a maculopapular rash. METHODS: Skin tests: prick, intradermal and patch tests as well as a single-blind oral challenge test (OCT) were performed. RESULTS: Skin tests were negative. The OCT was necessary to confirm the diagnosis. Interestingly, the challenge test elicited an FDE-type lesion instead of a maculopapular rash. CONCLUSIONS: Our findings could reflect 2 different clinical patterns of delayed allergic reactions, or, more probably, the initial phase of a unique clinical entity that was stopped by the corticosteroids prescribed during the challenge. However, we were unable to confirm these hypotheses. The uncommon anatomical site of the lesions (hard palate) is noteworthy. Some relevant patents are also summarized in this paper.

Mice that lack activity of alphavbeta6- and alphavbeta8-integrins reproduce the abnormalities of Tgfb1- and Tgfb3-null mice.

The arginine-glycine-aspartate (RGD)-binding integrins alphavbeta6 and alphavbeta8 activate latent TGFbeta1 and TGFbeta3 in vivo, but it is uncertain whether other RGD-binding integrins such as integrins alphavbeta5 and alphavbeta3 activate these TGFbeta isoforms. To define the combined role of alphavbeta6- and alphavbeta8-integrin in TGFbeta activation, we analyzed mice lacking function of both integrins by means of gene deletion and/or pharmacologic inhibition. Most Itgb6-/-;Itgb8-/- embryos die at mid-gestation; those that survive develop cleft palate-as observed in Tgfb3-/- mice. Itgb8-/- mice treated with an anti-alphavbeta6-integrin antibody develop severe autoimmunity and lack Langerhans cells-similar to Tgfb1-null mice. These results support a model in which TGFbeta3-mediated palate fusion and TGFbeta1-mediated suppression of autoimmunity and generation of Langerhans cells require integrins alphavbeta6 and alphavbeta8 but not other RGD-binding integrins as TGFbeta activators.

Expression of interleukin-8 and its receptor IL-8RA in chronic hyperplastic candidosis.

INTRODUCTION: Neutrophils are the main opponents of Candida albicans in chronic hyperplastic candidosis. They migrate from the circulation to the epithelium where they form microabscesses. We therefore hypothesized that the neutrophil chemokine interleukin-8 (IL-8) might play a role in the neutrophil-Candida interaction. METHODS: Biopsies from patients with chronic hyperplastic candidosis (n = 10) were stained using the avidin-biotin-peroxidase complex protocol for IL-8 and IL-8 receptor A and were compared to healthy control mucosa (n = 3). A set of C. albicans agar sections was similarly analysed. RESULTS: In chronic hyperplastic candidosis lesions IL-8 was strongly expressed in both vascular endothelium and mucosal epithelium. Many resident and immigrant inflammatory cells, including intraepithelial neutrophils, were IL-8 receptor A positive. In addition, IL-8 (or an analogue) was found in the candidal mother cell in chronic hyperplastic candidosis and in agar, whereas the tips of the hyphae expressed IL-8 receptor A (or an analogue). CONCLUSION: IL-8 may play a role in the recruitment of neutrophils from the vascular compartment to the epithelial microabscesses. C. albicans may have developed an ability to sense IL-8. The IL-8 ligand-receptor interaction may help to direct the growth of the IL-8-receptor-containing tips of the hyphae away from the IL-8-producing candidal cell body (a centrifugal growth pattern to facilitate host tissue penetration). Later, this ability might help to keep the vulnerable hyphal tips away from areas with high concentrations of host IL-8 and candidacidal neutrophils. We suggest that this phenomenon, in contrast to chemotropism, is named chemophobia.

Nasal response to allergen and hyperosmolar challenge.

Rhinitis causes both clinical and social discomfort to patients, and in clinical practice is often underdiagnosed. We have examined a simple method for the assessment of a positive nasal provocation test to help in the diagnosis of rhinitis. In patients with histories suggestive of house dust mite (HDM) sensitivity and positive skin-prick tests or specific IgE to Dermatophagoides pteronyssinus, there was a fall in nasal inspiratory peak flow (NIPF) following nasal challenge with allergen. This was not seen in control subjects or in pollen-sensitive patients when challenged with house dust mite. Frequency of sneezing and degree of rhinorrhoea increased in these patients following challenge, and based on these findings we propose a simplified scoring system for the diagnosis of allergic rhinitis. We examined non-specific nasal reactivity using hyperosmolar solutions as a challenge system and found that allergic subjects responded with a fall in NIPF, although the clinical response was not identical to that seen with allergen. Control subjects did not respond to hyperosmolar challenge.

[Appearance of entodermal antigen in the mouth mucosa of dogs in recurrent spontaneous stomatitis]. / Poiavlenie entodermal'nogo antigena v slizistoi obolochke polosti rta sobak pri retsidiviruiushchem spontannom stomatite.

An additional component absent in the same areas of the mouth under normal conditions appeared in dogs with spontaneous stomatitis in the ectodermal derivatives (mucosa of the cheeks, tongue and the hard palate). This component proved to be fully identical to the antigens of the mucosa of the soft palate, esophagus, stomach, small and large intestine, which were entodermal derivatives. No entodermal antigen was revealed in the other organs and tissues under study.

Subepithelial B cells in the human palatine tonsil. I. Morphologic, cytochemical and phenotypic characterization.

This study describes the purification of a subset of tonsillar B cells which share phenotypic, morphologic and cytochemical features with subepithelial (SE) B cells. These cells, which represented the 5-10% of the total tonsillar B cells, were found in the Percoll gradient fraction of highest density, together with resting follicular mantle (FM) B cells. The latter B cells, however, expressed surface CD5 and could be removed by an immune rosetting procedure. The remaining small CD5- B cells had a surface phenotype (IgM+, IgD+, CD23-, CD38+/-, CD10-, CD44+) that was different from that of FM (IgM+, IgD+, CD23+, CD39+, CD38-, CD10-, CD44+2) and of germinal center (GC) (CD23-, CD39-, CD38+, CD10+, CD44+/-, IgG+) B cells isolated from the same cell suspensions. Furthermore, the absence of surface activation markers (CD71 and CD69) and of surface IgG allowed us to distinguish small CD5- B cells from activated and memory cells migrating within Percoll fractions of lower density. In situ immunohistochemical studies revealed that B cells with an identical phenotype as that of small CD5- B cells could be detected predominantly in the SE region (lamina propria) of the tonsil, and also within the epithelium lining the cryptae. This area was also comprised of a relatively minor proportion of activated B cells, not found in the small CD5- B cell fraction owing to the separation procedure used. Consistent with the notion that the SE area could be a site of B cell activation was also the presence of activated macrophages and of plasma cells. Thirty to forty percent of small CD5- B cells isolated in suspension were positive for the endogeneous alkaline phosphatase (ALP) activity. In contrast, only a few FM B cells were ALP+, while GC cells were consistently ALP-. In situ studies also demonstrated a prevalent expression of ALP activity by the B cells in the SE area. At the ultrastructural level, small CD5- B cells were clearly different from both FM and GC B cells. They displayed a cytoplasm more extended than that of FM B cells with abundant endosomes and plasma membrane projections, and a speckled pattern of nuclear heterochromatin distribution. When fixed tissue sections were examined, cells with identical ultrastructural features could be demonstrated in the tonsillar lamina propria. Collectively, the above data demonstrate an identity of features between the small CD5- B cells isolated in suspension and SE B cells analyzed in situ. Since tonsillar SE B cells are generally thought to represent the homolog of the extrafollicular B cells (including those of the splenic marginal zone), these studies may provide new opportunities for functional studies on this so far incompletely characterized B cell subset.

Localization of H-2Kk in developing mouse palates using monoclonal antibody.

Using monoclonal antibodies to H-2Kk antigen, we sought to develop a reproduceable method of in situ localization in embryonic tissue and to determine whether there are specific patterns of H-2 localization in time and space in the developing palatal tissues of B10.A(H-2a) embryonic mice, with and without corticosteroid pretreatment at 12 days gestation. Our procedure employs ethanol-glacial acetic acid fixation, paraplast embedding, and enzymatic predigestion with purified hyaluronidase and neuraminidase. H-2 antigens were detected in palatal mesenchyme as well as basement membranes but not in oral or nasal epithelium. The pattern of distribution in mesenchyme of untreated embryos changed with progressive shelf development vertical leads to horizontal leads to epithelial fusion leads to epithelial seam degeneration leads to mesenchymal confluence. Although the palatal shelves of treated embryos remained vertical, corticosteroid treatment does not appear to alter the detectable spatiotemporal distribution of H-2 antigens in developing palates of embryonic B10.A mice.

Monoclonal antibodies recognising stage and region specific epitopes in embryonic mouse palatal epithelial cells.

Four monoclonal antibodies raised against murine embryonic palatal epithelium were used to stain frontal cryosections of embryonic mouse heads (d 11-15). One antibody (6A11) recognised the nasal epithelium at the angle of the palate prior to shelf elevation (embryonic d 11-d 13) and the epithelia at the tips of the approximated shelves (embryonic d 14.5). Two further antibodies (2H6 and 3H2) recognised epitopes on the entire palatal epithelium until shelf elevation (embryonic d 14.5) when their expression ceased. The epitope recognised by antibody 6D3 was absent from the palatal epithelium until embryonic d 13 when it displayed region specific expression, being present on the nasal aspect in the midpalate and the tip of the palate posteriorly. On embryonic d 14.5 staining of the medial edge epithelia was present in all regions. Whilst the nasal palatal epithelium stained in the anterior and mid regions, only patchy staining of the oral epithelium was detected. By embryonic d 15 staining was present throughout the palatal epithelia. These antibodies are directed against intracellular epitopes, possibly keratins. Indeed, immunoblotting assays revealed that antibody 2H6 recognised keratin 18. The developmental regulation of the epitopes recognised by the antibodies corresponds with differentiative events occurring during murine palatogenesis.

Immunocytochemical localization of serotonin-like immunoreactivities in the ciliated epithelium of the frog palatine mucosa.

Immunocytochemical localization of serotonin (5-HT)-like immunoreactivities was studies in the ciliated epithelium of the frog palatine mucosa by the peroxidase anti-peroxidase (PAP) method. 5-HT-like immunoreactivity was found only in the small granular vesicles (100-150 nm in diameter) and not in any mature large secretory granules or in other cell organellae in the goblet cells. No 5-HT-like immunoreactivities were found in any other epithelial and secretory cells in the palatine epithelium. It appears therefore that 5-HT-like immunoreactive granular vesicles have certain physiological effects on the ciliary movement of the ciliated cells or in the goblet cells.

Particularity of local immunity in the nasopharynx. Parallel study of surface receptors and cell-mediated immune responses in cells derived from palatine or pharyngeal tonsils and blood.

Immunological functions of the pharyngeal tonsil, palatine tonsils and blood leucocytes of children undergoing tonsillectomy were evaluated by determining T or B lymphocytes, the response to mitogens, and the cell-mediated immunological responses to tuberculin. In all the test systems used similar results were obtained with cells derived from either the palatine or pharyngeal tonsils. The mean percentage of T lymphocytes was significantly higher in the peripheral blood than in tonsils, but the reverse was true of B lymphocytes. The reaction to PHA was lower in tonsillar cell culture than in blood cell culture, but tonsillar cells reacted better to Con A than blood cells. In lymphocyte transformation tests tonsillar cells reacted to specific antigen (tuberculin) and this reaction was significantly higher than that of the parallelly tested blood lymphocytes. Further, in about 50% of the children tested, tuberculin caused migration inhibition of the mixture containing tonsillar cells and guinea pig peritoneal cells. Surprisingly, nearly identical results were obtained if migration inhibition test was performed with tonsillar cells alone. Consequently, poorly migrating tonsillar cells are nevertheless usable for direct migration inhibition testing.

[Sialadenitis at an unusual site in acute infectious mononucleosis]. / Sialadenitis ungewöhnlicher Lokalisation bei frischer Mononukleoseinfektion.

Infectious mononucleosis is found worldwide. The clinical manifestations vary widely. We report a case with impressive swelling of the hard and soft palate. Inflammation in the region of the efferent ducts of the palatinal glands resulted in congestion in the region of the mucinous salivary glands. The subsequent secretory stasis caused degeneration of the acini and rupture of a salivary retention cyst. The surrounding connective tissue was soaked with mucin, and unspecific chronic granular inflammation was found. Immunohistochemical examination with a monoclonal EBV antibody was necessary to show that the exceptional clinical picture was due to infectious mononucleosis.

Subepithelial B cells in the human palatine tonsil. II. Functional characterization.

This study investigates the main functional features of subepithelial (SE) B cells and compares them with those of purified germinal center (GC) and follicular mantle (FM) B cells isolated from the same tonsils. Unlike FM B cells, SE B cells failed to produce polyspecific antibodies in vitro; unlike GC B cells, SE B cells expressed high levels of Bcl-2 and failed to undergo spontaneous apoptosis in vitro. The most striking function of SE B cells was their ability to produce IgM antibodies to T cell-independent type-2 (TI-2) (but not to TI-1) antigens (Ag). These antibodies could not be detected when both FM and GC B cells were stimulated with TI-2 Ag in vitro. Moreover, B cells isolated from peripheral blood were unable to mount a response to TI-2 Ag. The latter finding is consistent with the observation that B cells with the phenotypic features of SE B cells were virtually absent in the peripheral blood and emphasizes the notion that SE B cells belong to a subset of non-recirculating B cells. SE B cells were by far superior to FM B cells in mixed lymphocyte reaction (MLR) stimulation of allogeneic T cells in vitro, although they were not as efficient as dendritic cells (DC). In order to stimulate T cells efficiently, SE B cells had to be exposed to anti-mu antibody, a treatment which induced expression of activation markers such as CD80, CD86, CD69 and CD39, usually absent in resting SE B cells. CD80 and CD86 molecules expressed by SE B cells participated in the chain of events required to promote the proliferation of allogeneic T cells as demonstrated by inhibition tests with the appropriate mAb. The expression of CD80 and CD86 by anti-mu-treated SE B cells was not, however, the sole explanation for their good antigen presenting capacities since the exposure of FM B cells to anti-mu antibody also induced expression of these surface structures. Nevertheless, these cells failed to become good MLR stimulators. Collectively, the above data contribute further to the characterization of a distinct subset of tonsillar B cells which resemble, both phenotypically and functionally, the B cells of the splenic marginal zone.