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Recurrent or chronic oral pain is a great burden for patients. Recently, the links between epithelial barrier loss and disease were extended to include initiation and propagation. To explore the effects of pathohistological changes in oral epithelia on pain, we utilized labial mucosa samples in diagnostic labial gland biopsies from patients with suspected Sjögren's syndrome (SS), because they frequently experience pain and discomfort. In most labial mucosa samples from patients diagnosed with SS, disseminated epithelial cellular edema was prevalent as ballooning degeneration. The disrupted epithelia contained larger numbers of infiltrating macrophages in patients with oral pain than in patients without pain. Immunohistochemistry revealed that edematous areas were distinct from normal areas, with disarranged cell–cell adhesion molecules (filamentous actin, E-cadherin, β-catenin). Furthermore, edematous areas were devoid of immunostaining for transient receptor potential channel vanilloid 4 (TRPV4), a key molecule in adherens junctions. In an investigation on whether impaired TRPV4 affect cell–cell adhesion, calcium stimulation induced intimate cell–cell contacts among oral epithelial cells from wild-type mice, while intercellular spaces were apparent in cells from TRPV4-knockout mice. The present findings highlight the relationship between macrophages and epithelia in oral pain processing, and identify TRPV4-mediated cell–cell contacts as a possible target for pain treatment. [ABSTRACT FROM AUTHOR]

Objectives: Mikulicz’s disease (MD) was considered to be a subtype of Sjögren’s syndrome (SS), based on histopathological similarities. However, recent studies have indicated that patients with MD show high serum IgG4 concentration, and suggested that MD is one of “IgG4-related disease” and distinguishable from SS. Therefore, we clinically and histopathologically examined the disease states of MD and SS in detail. Materials and methods: Twenty patients with Mikulicz’s disease and 18 with SS were comparatively studied to determine clinical characteristics in MD patients. Results: Sialography in MD patients did not show the “apple-tree sign” typically seen in SS. Serologically, high serum IgG4 levels but not anti-SS-A or anti-SS-B antibodies were observed in MD. SS showed lymphocytic infiltration of various subsets with atrophy or severe destruction of the acini, while MD showed selective infiltration of IgG4+ plasma cells with hyperplastic germinal centers and mild acini destruction. Corticosteroid treatment of MD reduced IgG and IgG4 levels and improved salivary function. A negative correlation between disease duration and increasing rate of salivary flow was observed in MD. Conclusions: These results suggested that the pathogenesis of MD might be different from those of SS. Clinical Relevance: early diagnosis and treatment of MD is important for the improvement of salivary function. [ABSTRACT FROM AUTHOR]

The sporulation inhibitory gene spi in the pock-forming conjugative plasmid pSA1.1 of Streptomyces azureus was introduced into cells via a high or low copy number vector to examine the effect of gene dosage on the growth of Streptomyces lividans TK24 as a host. In transformants carrying a high spi copy number, nutrient mycelial growth was inhibited, as was morphological differentiation from substrate mycelium to aerial mycelium on solid media. The degree of inhibition depended on the spi gene dosage, but the presence of pSA1.1 imp genes, which encode negative repressor proteins for spi, relieved the inhibition. Confocal images of Spi tagged with enhanced green fluorescent protein in cells on solid media revealed that spi expression was initiated at the time of elongation of substrate mycelium, that its expression increased dramatically at septation in aerial hyphae, and that the expression was maximal during prespore formation. Expression of spi covered the whole of the hyphae, and the level of expression at the tip of the hyphae during prespore formation was about sixfold greater than during substrate mycelial growth and threefold greater than during aerial mycelial growth. Thus, localized expression of spi at particular times may inhibit sporulation until triggering imp expression to repress its inhibitory effects. [ABSTRACT FROM AUTHOR]

The article details a study which investigated if induction of systemic inflammation accelerates the development of Sjögren's syndrome (SS) in genetically susceptible mice. The study treated female mice with either Freund's incomplete adjuvant (IFA) or phosphate buffered saline (PBS). The mice were killed at different time points and underwent sialadenitis and salivary gland-infiltrating cells tests. It concluded that generalized inflammatory stimuli can accelerate the development of SS-like disease.

In the labial salivary glands (LSGs) of 16 primary and 18 secondary Sjögren's syndrome (SS) patients, infiltrating lymphocytes were histologically and immunohistochemically examined; also, the serum levels of rheumatoid factor, antinuclear antibodies, anti-DNA antibodies, anti-SS-A and anti-SS-B antibodies, and immunoglobulins (including IgG, IgM and IgA) were all assayed. An immunohistochemical analysis of the lymphocyte subsets in LSGs revealed that severe lymphocytic infiltration was frequently accompanied by marked B cell accumulation both in primary and secondary SS patients. Furthermore, local B cell accumulation was also closely associated with elevated levels of anti-SS-A and anti-SS-B antibodies and IgG, and this association was statistically significant in the group with primary SS but not in the group with secondary SS. Thus, local lymphocytic infiltration, especially B cell accumulation, in the salivary glands is suggested to be involved in serological abnormalities in primary SS, while complicated autoimmune diseases other than SS may also be involved in serological abnormalities in secondary SS. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinomas (SCC) are often infiltrated by a large number of T lymphocytes. To clarify the nature of the tumour-infiltrating lymphocytes (TIL), we examined T cell receptor (TCR) Vα and Vβ gene usage by TIL and peripheral blood mononuclear cells (PBMC) obtained from 10 patients with oral SCC. We obtained RNA from TIL and PBMC, synthesized complementary DNA, and used the polymerase chain reaction (PCR) method with a panel of primers specific for the V gene segment subfamily (Vα1 - 18/Vβ1 - 20). We thus found that TIL showed more restricted usage of Vβ gene families in contrast to PBMC of the same patients while two unique Vβ gene (Vβ6 and Vβ5.2) segment transcripts were overexpressed in the TIL of more than half of the patients. On the other hand, no major difference was observed in the Vα gene usage between the TIL and PBMC of most patients. To characterize these T cell subpopulations with unique Vβ gene segment transcripts further, we sequenced the complementarity-determining region 3 in Vβ6-Cβ and Vβ5.2-Cβ PCR products derived from TIL and PBMC of two selected patients in each case. Although no usage of the conserved amino acid sequence by TIL was detected, the frequent use of Vβ6/Jβ1.1 in one patient and the Vβ6/Jβ2.7 gene segments in another patient was observed. Regarding the Vβ5.2 transcripts, obtained from the other two patients, no preferential usage of specific Jβ gene segments by TIL was observed. These results suggest that the unique T cell populations are amplified in patients with oral SCC, possibly as a consequence of an in situ immune reaction. [ABSTRACT FROM AUTHOR]