Epithelial Cell Apoptosis in Recurrent Aphthous Ulcers.

A recurrent aphthous ulcer (RAU) is a common inflammatory ulcerative lesion affecting oral mucosa. We studied the eventual apoptosis of epithelial cells from the point of view of ulcer and inflammation. RAU lesions and healthy mucosa samples were immunostained for caspase-3 and high-mobility group box 1 (HMGB1). DNA nicks were identified using TUNEL staining. We studied the effects of tumor necrosis factor α (TNFα) and interferon γ (IFNγ) on the toll-like receptor 2 and 4 (TLR2 and TLR4) expression of human oral SCC-25 keratinocytes. We also studied the effects of self-DNA, all-thiol-HMGB1, and disulfide-HMGB1 on epithelial cells, with or without IFNγ. At the edge of RAU lesions, all epithelial cell layers were caspase-3(+), TUNEL(+), and HMGB-1(+) and had widened intercellular spaces. In contrast, healthy epithelial cells were negative for caspase-3 and TUNEL staining. HMGB1 was seen in only the basal cell layers, and the cells retained close cell-to-cell contacts. Self-DNA increased TNF-α mRNA (P = 0.02) in SCC-25 cells. Both TNFα and IFNγ (P = 0.01) increased TLR2. Upon TNFα stimulation, SCC-25 cells lost their nuclear HMGB1 staining. HMGB1 did not increase IL-8, IL-6, or TNF-α mRNA in SCC-25 cells, which was unaffected by the presence of IFNγ. We conclude that in healthy epithelium, the most superficial cells at the end of their life cycle are simply desquamated. In contrast, RAU is characterized by top-to-bottom apoptosis such that dead cells may slough off, leading to an ulcer. Because of a lack of scavenging anti-inflammatory macrophages, apoptotic cells probably undergo secondary necrosis releasing proinflammatory danger signals, which may contribute to the peripheral inflammatory halo. This is supported by self-DNA-induced TNFα synthesis. In contrast to TLR4- and TLR2-binding lipopolysaccharide used as a positive control, disulfide-HMGB1 did not stimulate proinflammatory cytokines.

Sjögren's syndome and extragonadal sex steroid formation: a clue to a better disease control?

Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphoplasmacytoid focal adenitis leading to mucosal dryness, with 9:1 female dominance and peak incidence at menopause. Due to autoimmune adenitis it can be speculated that the normal epithelial cell renewal has failed, possibly as a result of local intracrine failure to process dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). Local intracrine/-cellular DHT deficiency seems to predispose to SS if estrogens are low, in menopausal women and in men. This intracrine failure could be the initial noxious stimulus, factor X, initiating the development of SS. Abnormal release and presentation of exocrine gland-derived antigens (Ag-epitopes), in a complex with major histocompatibility complex class II (MHC II), by migratory dendritic cells (DC) activates T-cells in the regional lymph nodes. B-cells with the same specificity capture and present self-Ag to Th-cells which provide T-cell help. B-cells transform to plasma cells and start to produce autoantibodies (Ab) against these T-cell-dependent Ag. Ab against SS-A/Ro and SS-B/La ribonucleoproteins occur only in HLA-DQw2.1/DQw6 heterozygous individuals, but hY-RNA and RNA polymerase III transcripts in these Ag may in all SS patients stimulate toll-like receptors (TLR) 7 and 9 of the plasmacytoid DCs, because IFN-α and IFN-signature are produced. CD8+αEß7+cytotoxic T-cells activated via cross-presentation recirculate to attack intracrine-deficient, apoptotic epithelial cells expressing self-Ag on their surface. Exocrine glands fall into the sphere of mucosal/gut-associated lymphatic tissue. This together with immune complexes spreads the immunological memory/aggression to extra-glandular sites explaining the systemic nature of the syndrome. Secondary SS could be explained by disturbed lymphocyte recirculation. There is no conclusive evidence that SS in those few men affected is more severe than in women, suggesting that sex steroid endo-/intracrinology has its major impact on the target tissue, not on immune modulation. This article is part of a Special Issue entitled 'Essential role of DHEA'.

Histamine H4 receptor in oral lichen planus.

OBJECTIVES: Oral lichen planus (OLP) is an autoimmune disease characterized by a band-like T-cell infiltrate below the apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high-affinity histamine H4 receptors (H4 Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T-cell cytokines. MATERIALS AND METHODS: Immunohistochemistry and immunofluorescence staining, image analysis and quantitative real-time polymerase chain reaction of tissue samples and cytokine-stimulated cultured SCC-25 and primary human oral keratinocytes. RESULTS: H4 R immunoreactivity was weak in OLP and characterized by mast cell (MC) hyperplasia and degranulation. In contrast to controls, H4 R immunostaining and MC counts were negatively correlated in OLP (P = 0.003). H4 R agonist at nanomolar levels led to a rapid internalization of H4 Rs, whereas high histamine concentration and interferon-γ decreased HRH4 -gene transcripts. CONCLUSION: Healthy oral epithelial cells are equipped with H4 R, which displays a uniform staining pattern in a MC-independent fashion. In contrast, in OLP, increased numbers of activated MCs associate with increasing loss of epithelial H4 R. Cell culture experiments suggest a rapid H4 R stimulation-dependent receptor internalization and a slow cytokine-driven decrease in H4 R synthesis. H4 R may be involved in the maintenance of healthy oral mucosa. In OLP, this maintenance might be impaired by MC degranulation and inflammatory cytokines.

Increased beta 2 defensin in recurrent aphthous ulcer.

OBJECTIVES: It was hypothesized that beta 2 defensin (BD-2) is increased in RAU lesions compared with healthy controls to promote anti-microbial host defence. METHODS: RAU and control mucosa samples were subjected to quantitative real-time PCR and immunostained for BD-2, CD68, mast cell tryptase and 4-hydroxynonenal (4HNE). The effect of tumour necrosis factor-α (TNF-α) ± interleukin-17C (IL-17C), without and with vitamin K3, was studied on BD-2 expression in epithelial SCC-25 cells. RESULTS: Although BD-2 mRNA did not differ between healthy and RAU mucosa, BD-2 stained strongly in acute-phase RAU epithelium (P = 0.001). In controls, subepithelial BD-2(+) cells were mast cells and macrophages, whereas in RAU, most infiltrating leucocytes were BD-2(+) (P = 0.004). In cell culture, BD-2 was increased 124-fold by TNF-α (P < 0.0001) and 208-fold synergistically together with IL-17C (P < 0.0001). 4HNE staining of RAU epithelium was not significantly increased, and vitamin K3-induced reactive oxygen species (ROS) did not affect BD-2. CONCLUSIONS: Anti-microbial BD-2 was not affected by oxidative stress but was highly increased in the epithelial and immigrant cells in the acute-phase RAU lesions, probably in part synergistically by TNF-α and epithelial IL-17C, which are known to be induced by activation of danger-signal receptors by pathogen- and/or damage-associated molecular patterns.

Scandinavian Fellowship for Oral Pathology and Oral Medicine: guidelines for oral pathology and oral medicine in the dental curriculum.

In Scandinavia, as in many European countries, most patients consult their general dentist once a year or more. This gives the dentist a unique opportunity and an obligation to make an early diagnosis of oral diseases, which is beneficial for both the patient and the society. Thus, the dentist must have knowledge of clinical symptoms, local and systemic signs and clinical differential diagnoses to make an accurate diagnosis. The dentist must be competent in selecting appropriate diagnostic tests, for example, tissue biopsy and microbiological samples, and conducting them correctly, as well as in interpreting test results and taking appropriate action accordingly. Furthermore, the dentist must be aware of diseases demanding multidisciplinary cooperation and be able to recognise his/her professional limitation, and to refer to other specialists when required. The dental curriculum changes over time as new approaches, treatments and diagnostic possibilities develop. Likewise, the role of the dentist in the community changes and may vary in different countries. As members of the Scandinavian Fellowship for Oral Pathology and Oral Medicine and subject representatives of oral pathology and oral medicine, we feel obliged to contribute to the discussion of how the guidelines of the dental curriculum support the highest possible standards of dental education. This article is meant to delineate a reasonable standard of oral pathology and oral medicine in the European dental curriculum and to guide subject representatives in curriculum development and planning. We have created an advisory topic list in oral pathology and oral medicine.

Scandinavian Fellowship for Oral Pathology and Oral Medicine: statement on oral pathology and oral medicine in the European Dental Curriculum.

BACKGROUND: For many years, dentists have migrated between the Scandinavian countries without an intentionally harmonized dental education. The free movement of the workforce in the European Union has clarified that a certain degree of standardization or harmonization of the European higher education acts, including the dental education, is required. As a result of the Bologna process, the Association for Dental Education in Europe and the thematic network DentEd have generated guidelines in the document 'Profile and Competences for the European Dentist' (PCD). This document is meant to act as the leading source in revisions of dental curricula throughout Europe converging towards a European Dental Curriculum. In order to render the best conditions for future curriculum revisions providing the best quality dentist we feel obliged to analyse and comment the outlines of oral pathology and oral medicine in the PCD. METHODS: The representatives agreed upon definitions of oral pathology and oral medicine, and competences in oral pathology and oral medicine that a contemporary European dentist should master. The competences directly related to oral pathology and oral medicine were identified, within the PCD. RESULTS: The subject representatives suggested eighteen additions and two rewordings of the PCD, which all were substantiated by thorough argumentation. PERSPECTIVES: Hopefully, this contribution will find support in future revisions of the PCD in order to secure the best quality dental education.

Towards open information management in health care.

The utilization of information technology as tool in health care is increasing. The main benefits stem from the fact that information in electronic form can be transferred to different locations rapidly and from the possibility to automate certain information management tasks. The current technological approach for this automation relies on structured, formally coded representation of information. We discuss the limitations of the current technological approach and present a viewpoint, grounded on previous research and the authors' own experiences, on how to progress. We present that a bottleneck in the automation of the management of constantly evolving clinical information is caused by the fact that the current technological approach requires the formal coding of information to be static in nature. This inherently hinders the expandability of the information case space to be managed. We present a new paradigm entitled open information management targeting unlimited case spaces. We also present a conceptual example from clinical medicine demonstrating open information management principles and mechanisms.

Soft tissue reactions to bioactive glass 13-93 combined with chitosan.

The aim of this study was to evaluate rabbit soft tissue reactions to bioactive glass 13-93 mesh by using a histological and immunohistochemical analysis. Bioactive glass (13-93) mesh fixed with 3 wt % chitosan was implanted into the dorsal subcutaneous space of New Zealand White rabbits (n=18) for six, 12, and 24 weeks, respectively. After 6 weeks the bioactive glass remnants were surrounded by foreign-body granuloma with eosinophilic granulocytes. After 12 and 24 weeks the implanted material was mainly absorbed, but, if any particles still remained the foreign-body reaction was notably milder. Yet, a mild chronic inflammatory infiltrate was present. Matrix metalloproteinase (MMP) -2, -3, -13 and tissue inhibitory protein (TIMP-1 and -2) expressions were studied by immunohistochemistry. MMP-3, -13, TIMP-1, and -2 positivity were detected throughout the follow-up period. MMP-2 positivity was only occasionally seen in the 24 week samples, which is constitutively expressed but is not related to inductive MMP-3 and -13 cascade. The presence of eosinophilic granulocytes in some of the samples raises the possibility of an allergic reaction to the materials. MMP-3 and -13 are suggested to participate in the host reaction to either bioactive glass or chitosan.

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.

A histological and immunohistochemical study of tissue reactions to solid poly(ortho ester) in rabbits.

In many cases only the temporary presence of a biomaterial is needed in tissue support, augmentation or replacement. In such cases biodegradable materials are better alternatives than biostable ones. At present, biodegradable polymers are widely used in the field of maxillofacial surgery as sutures, fracture fixation devices and as absorbable membranes. The most often used polymers are aliphatic polyesters, such as polyglycolic acid (PGA) and polylactic acid (PLA). Poly(ortho ester) is a surface eroding polymer, which has been under development since 1970, but is used mostly in drug delivery systems in semisolid form. The aim of this study was to evaluate the tissue reactions of solid poly(ortho ester) (POE), histologically and immunohistochemically. Resorption times and the effect of 2 different sterilization methods (gamma radiation and ethylene oxide) upon resorption were also evaluated. Material was implanted into the tibia and subcutaneously into the mandibular ramus area of 24 rabbits. Follow-up times were 1-10, 14 and 24 weeks. Histological studies showed that POE induces a moderate inflammation in soft tissue and in bone. At 24 week follow-up, inflammation was mild in soft tissue and moderate in bone. In immunohistochemical studies, no highly fluorescent layer of tenascin or fibronectin was found adjacent to the implant. Resorption of gamma-sterilized rods was faster than ethylene oxide-sterilized rods. The total resorption time was more than 24 weeks in both groups. Clinically the healing was uneventful and the implants the well tolerated by the living tissue. This encourages these authors to continue studies with this interesting new material to search for the ideal material for bone filling and fracture fixation.

The copolymer of epsilon-caprolactone-lactide and tricalcium phosphate does not enhance bone growth in mandibular defect of sheep.

In the field of craniomaxillofacial and orthopaedic surgery there is a constant need for bone or bone substitute. At the present, the most effective way to enhance bone healing clinically is to use autogenous bone grafts. The problems associated with the use of these autografts are donor site morbidity, limited supply and need for a second operative site. Currently there are several different synthetic products commercially available in the market; nevertheless, none of them is ideal for filling bone defects. Therefore, search for new synthetic materials for bone replacement is necessary. A mixture of tricalcium phosphate (TCP) and epsilon-caprolactone-lactide copolymer P(epsilon -CL/DL-LA) was prepared and implanted in critical size mandibular bone defects in twelve sheep. Contralateral side was used as a control. Follow-up times for histological and radiological studies were 9, 14, 24 and 52 weeks. We found that the implanted material did not enhance bone formation compared to control site. We also confirmed that defect size was of critical size, since there was no complete healing of the control site either. The results do not encourage us to continue our studies with the mixture of TCP and P(epsilon-CL/DL-LA) as a filling material for bone defects. Therefore the search for the ideal material is still ongoing.

Oral findings in coeliac disease and Sjögren's syndrome.

OBJECTIVE: Both coeliac disease (CD) and Sjogren's syndrome (SS) have an autoimmune background and increased risk of oral mucosal and dental abnormalities. Individuals suffering concomitantly from CD and SS could even be at a higher risk. STUDY DESIGN: Oral mucosal and dental abnormalities were examined in 20 patients with CD + SS (mean age 61 years) and compared with age- and sex-matched controls with either CD or SS. RESULTS: Oral mucosal changes were most common in SS (80%), followed by CD + SS (65%) and CD (40%). Coeliac-type dental enamel defects were found in 89% in CD + SS and in 88% in CD compared with only 25% in SS (P < 0.001). The median number of teeth was six in the CD + SS, 24 in the CD and 22 in the SS group. The DMF index was higher (P < 0.005) in the CD + SS than in the CD group. CD + SS was characterized by higher salivary flow rate (P < 0.001) and lower inflammatory focus score in the salivary glands (P < 0.01) than SS. CONCLUSIONS: The co-occurrence of CD and SS should be recognized because of its effects on dental and oral mucosal health. A lower salivary gland inflammatory focus score and higher salivary flow rate in CD + SS than in SS suggests that a gluten-free diet treatment may alleviate autoimmune inflammation.

HLA-DRB1* alleles and temporomandibular joint erosion in patients with various rheumatic diseases.

OBJECTIVE: To investigate the association between HLA antigens and temporomandibular joint (TMJ) erosion, salivary composition, and focal sialadenitis in patients with rheumatic diseases. METHODS: Eighty-four patients, 24 with rheumatoid arthritis (RA), 19 with mixed connective tissue disease (MCTD), 19 with ankylosing spondylitis (AS), and 22 with spondyloarthropathy (SPA) were studied. Each patient underwent clinical examination of the masticatory system, unstimulated and stimulated saliva collection, and minor salivary gland biopsy. Radiographs (OPTG) of the TMJ were obtained, and HLA allele (A, B, C and DRB1*) analysis was performed. Erosion in OPTG was scored from 0 (no erosion) to 4 (condyles totally eroded). In the analysis, scores 0-2 were grouped as normal or mild changes, and scores 3-4 as distinct erosions. One hundred healthy blood donors served as controls for HLA typing. RESULTS: Distinct erosion of the TMJ in OPTG was observed in 22 (27%) patients. It affected four (17%) of the 24 patients with RA, three (17%) of the 18 with MCTD, seven (37%) of the 19 patients with AS and eight (38%) of the 21 with SPA non-significant (NS). The mean erosion scores were 1.7 for RA, 1.3 for MCTD, 2.5 for SPA, and 1.6 for AS patients [probability (p) = 0.04]. The frequency of HLA-B27 antigen was higher in the AS and SPA patients, and that of HLA-DRB1*04 allele higher in RA patients than in control subjects. In the whole patient population, HLA-DRB1*01 allele was significantly associated with erosions 16/36 (44%) versus 6/46 (131%1) (p = 0.0014). In the SPA group, patients with HLA-DRBI*01 allele had a significantly higher occurrence of distinct erosions than patients without this allele [8/10 (80%) versus 0/11 (0%) (p = 0.0002)], whereas DRB1*06 was protective [0/8 (0%) versus 8/13 (62%) (p = 0.018)]. HLA-DRB1*04 was associated with increased salivary IgG in the RA patients. CONCLUSION: HLA antigens are significantly associated with the development of destructive lesions in the TMJ, as well as composition of saliva in patients with various rheumatic diseases.

Local primary (AL) amyloidosis in the palate. A case report.

Oral amyloidosis is usually presented in the tongue and is often regarded as a paraneoplastic phenomenon. We present a rare case of primary local amyloidosis in the palate of an 80-year-old male. No simultaneous general illnesses or malignancies were detected in spite of extensive assessments by specialists in internal medicine.

Candida yeasts in chronic periodontitis tissues and subgingival microbial biofilms in vivo.

The frequency of Candida infection in periodontal tissues of chronic periodontitis (CP) patients and the extent of candidal penetration into gingival tissues was studied. Tissue specimens collected from 25 CP patients during periodontal flap operations of initial periodontal therapy were examined by immunohistochemistry using Candida albicans-specific antibodies. Sections were also stained with periodic acid-Schiff (PAS) and subgingival plaque samples from 17 patients were cultured. Immunoreactivity for Candida was present in four of the 25 CP specimens (16%). Only one yeast-positive specimen was found when PAS-staining was used (4%) and two yeast-positive specimens were found with plaque culture (8%). Hyphal formation seemed essential and candidal hyphae were found to extend into the periodontal connective tissue. The degree and type of inflammation adjacent to the hyphae varied from a site and a patient to another. The sensitivity of specific antibodies was superior to PAS-stain or plaque culture in detection of Candida in tissues.

Differential expression of matrilysin-1 (MMP-7), 92 kD gelatinase (MMP-9), and metalloelastase (MMP-12) in oral verrucous and squamous cell cancer.

Squamous cell carcinoma (SCC) of the oral cavity is a highly invasive tumour of stratified squamous epithelium that spreads through degradation of the basement membrane (BM) and extracellular matrix (ECM). There are currently no reliable tissue or serum markers to predict whether the tumour has metastasized at the time of diagnosis. Verrucous carcinoma (VC) of the oral cavity is a rare low-grade variant of oral SCC that penetrates into the subepithelial connective tissue. Many matrix metalloproteinases (MMPs), such as MMP-1, -2, -7, -9, -13, and -14, as well as integrin receptors have been implicated in cancer invasion. Integrin alphavbeta6 is induced in SCC and appears to be involved in up-regulation of MMP-9 expression by oral keratinocytes and promotion of their migration. The aim of this study was to investigate whether the pattern of MMP expression or that of alphavbeta6 integrin contributes to the differences in the biological behaviour of oral SCC and VC. The results show that the less aggressive nature of oral VC may be connected to its MMP expression profile. Typically, VCs were devoid of epithelial MMP-3, -7, -9, -12 and -13 expression, compared with SCCs. MMP-19 was expressed by epithelial keratinocytes in hyperproliferative areas of verrucous hyperplasia, VC, and SCC, but was absent in the invasive cancer cell nests of SCC. MMP-26 was expressed by hyperproliferative keratinocytes in VC as well as by invasive cancer cells in SCCs. MMP-10 was expressed widely in the epithelium of all SCC specimens. alphavbeta6 integrin expression was also detected in some cases of epithelial hyperplasia but was significantly more abundant in cancers at the invasive front. The absence of MMP-7, -9 and -12 from epithelial cells may serve as a good prognostic marker of non-invasive oral carcinoma. Blocking the activity of invasion-specific MMPs or alphavbeta6 integrin might offer novel therapeutic modalities in early-stage oral carcinoma.

Tumor necrosis factor-alpha and its receptors, p55 and p75, in gingiva of adult periodontitis.

Tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, can stimulate matrix metalloproteinase synthesis and osteoclastic bone resorption. We hypothesized that elevated expression of TNF-alpha and its p55 and p75 receptors (TNF-R) in gingival tissue might associate with periodontitis. Immunohistochemistry was used for the study of the localization of TNF-alpha and its p55 and p75 TNF-R in adult periodontitis (AP) gingival tissue, in comparison with that in healthy control specimens. TNF-alpha and p55 TNF-R were detected in sulcular epithelial basal cells and in monocyte/macrophages, fibroblasts, and endothelial cells in the AP gingival tissue specimens, but mainly in fibroblasts and endothelial cells in control specimens. P75 TNF-R was occasionally found in monocyte/macrophage-like cells in gingival tissue specimens. The percentage of TNF-alpha-containing cells was not increased in AP compared with controls (13.2%+/-6.1% vs. 12.8%+/-7.6%), but, due to the increased cellularity of AP samples, the number of TNF-alpha positive cells/mm2 was clearly increased (1621+/-663 vs. 664+/-191, p > 0.001). Thus, AP gingival tissue has an elevated expression of TNF-alpha and especially its p55 receptor, suggesting that TNF-alpha may contribute to tissue degradation in periodontitis.

Focal sialadenitis in patients with ankylosing spondylitis and spondyloarthropathy: a comparison with patients with rheumatoid arthritis or mixed connective tissue disease.

OBJECTIVES: To investigate the occurrence of and risk factors for focal sialadenitis in patients with rheumatoid arthritis (RA), mixed connective tissue disease (MCTD), ankylosing spondylitis (AS), and spondyloarthropathy (SpA). METHODS: A total of 85 patients (25 with RA, 19 with MCTD, 19 with AS, 22 with SpA) participated in the study. Each patient filled out a questionnaire for eye and oral symptoms and for the use of medication, and was interviewed; other tests included Schirmer's test, laboratory tests, collection of unstimulated and stimulated whole saliva, and minor salivary gland biopsy. A focus score of > or =1 was regarded as an indicator of focal sialadenitis. RESULTS: Focal sialadenitis was observed in 68% (57/84) of all patients. It affected 80% (20/25) of the patients with RA, 94% (17/18) of those with MCTD, 58% (11/19) of those with AS, and 41% (9/22) of those with SpA (chi(2) test, p=0.0013). Salivary secretion correlated negatively with the focus scores-that is, severity of focal sialadenitis. Patients with focal sialadenitis had both decreased salivary secretion and decreased tear secretion significantly more often than did patients without (chi(2) test, p=0.0074 and p=0.048 respectively). Patients with positive rheumatoid factor (RF), antinuclear antibodies (ANA), or SSA or SSB antibodies had sialadenitis significantly more often than did patients with negative antibodies. In the subgroup of patients with AS or SpA, no associations were found between focal sialadenitis and the presence of these antibodies. CONCLUSION: In addition to patients with RA or MCTD, focal sialadenitis also affects a very high proportion of patients with AS or SpA. Focus scores are significantly higher in patients with RA or MCTD than in those with AS or SpA. A significant association exists between focal sialadenitis and RF, ANA, SSA and SSB. However, in the subgroup of patients with AS or SpA, no associations were found between focal sialadenitis and serological markers or clinical symptoms.

Expression and induction of collagenases (MMP-8 and -13) in plasma cells associated with bone-destructive lesions.

Matrix metalloproteinases (MMPs) collectively degrade extracellular matrix and basement membrane proteins in chronic inflammation and bone-destructive lesions. This study examined the ability of immunoglobulin-producing plasma cells, typically present in sites of chronic inflammation, to express collagenases (MMP-8 and -13) in vivo and in vitro. Phorbol-12-myristate-13-acetate, interleukin-6, and tumour necrosis factor-alpha and heparin with the tumour promoter or cytokines potently enhanced (up to nine-fold) MMP-8 and -13 expression by the RPMI 8226 myeloma cell line, as evidenced by western blotting and semi-quantitative reverse transcriptase-polymerase chain reaction. Immunohistochemical analysis and in situ hybridization revealed that plasma cells expressed MMP-8 and -13 focally in periapical granulomas, odontogenic cysts, and malignant plasmacytomas. MMP-8 and MMP-13 from plasma cells can participate in bone organic matrix destruction at sites of chronic inflammation and neoplastic growth. Since MMP-13 was more frequently expressed than MMP-8 in plasma cells of strongly recurring keratocysts and malignant plasmacytomas, it is concluded that plasma cell MMP-13 has a particularly important role in benign and malignant bone-destructive lesions.