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This paper reviews the literature and discusses patient selection for endosseous dental implants and the effect of systemic and local pathology on the success rate of dental implants. Endosseous dental implants may be preferable to conventional dentures in patients with compromised supporting bone or mucosa, xerostomia, allergy to denture materials, severe gag reflex, susceptibility to candidiasis, diseases affecting orofacial motor function or in patients who demand optimal bite force, esthetics, and phonetics. Conventional dentures or fixed partial prostheses may be preferable to endosseous dental implants in growing and epileptic patients and patients at risk of oral carcinoma, anaphylaxis, severe hemorrhage, steroid crisis, endocarditis, osteoradionecrosis, myocardial infarction, or peri-implantitis. A systematic approach to dental implant patient selection is outlined and centralized reporting of dental implant outcomes is recommended. [ABSTRACT FROM AUTHOR]

Background: Patients with atopic dermatitis (AD) are susceptible to infectious and inflammatory cutaneous comorbidities., Objective: The aim of the study was to describe the prevalence of cutaneous comorbidities associated with AD, including their relationship with AD severity., Methods: A retrospective cross-sectional analysis was performed using the Israeli Maccabi Healthcare Services database. Prevalent AD cases on December 31, 2017, were diagnosed with AD at any time since 1998 and had 1 or more recent (2013-2017) AD diagnoses. Dispensed AD treatments within 5 or fewer years served as a surrogate for AD severity. Cutaneous comorbidities in AD cases were compared with non-AD controls matched 1:1 on age, sex, and residential area. Among adults, comorbidities were compared across AD severity using multinomial logistic regression., Results: The eligible population included 94,483 patients with mild (57.7%), moderate (36.2%), or severe (6.1%) AD, and 94,483 matched non-AD controls. Skin infections, inflammatory skin conditions, cutaneous manifestations of AD, and sweat gland disorders were more prevalent ( P < 0.001) in patients with AD than in controls. Most cutaneous comorbidities that were more prevalent in adult patients with AD were also significantly ( P < 0.001) associated with AD severity., Conclusions: This study suggests that AD is associated with many infectious and inflammatory cutaneous comorbidities and highlights the relationship between AD severity and comorbidity prevalence., Competing Interests: Y.A.L. has received honoraria or fees as a consultant from AbbVie, Sanofi, and Genentech and as an advisory board member from Sanofi and Regeneron Pharmaceuticals, Pfizer, and Dexcel Pharma and has, without personal compensation, provided investigator services for Eli Lilly, Pfizer, and AbbVie. D.B.A. has received consultant fees from AbbVie. P.B.S. is a former employee of AbbVie and may own AbbVie stock and/or stock options. H.L., H.W., B.C., and A.D. are full-time employees of AbbVie and may own AbbVie stock and/or stock options. The other authors have no funding or conflicts of interest to declare., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Contact Dermatitis Society.)

Introduction: Real-world data on the epidemiology and economic burden of atopic dermatitis (AD) are limited. Here we describe the epidemiology and economic burden of AD using electronic healthcare data from Israel., Methods: A retrospective study was performed using the Maccabi Healthcare Services database. AD incidence in 2008-2017 and point prevalence (AD prev ) on 31 December 2017 were described using diagnosis codes for overall patients, and sex and age subgroups. For AD prev , severity was defined using recently dispensed treatments for AD. Annual healthcare resource utilization in AD prevalent patients was compared with non-AD matched controls using generalized linear modelling. Direct annual costs were estimated also., Results: AD incidence was 7.0/1000 person-years; overall prevalence was 4.4% (female patients 4.5%, male patients 4.3%; age 0 to less than 6 months, 0.9%; 6 months to less than 12 years, 11.0%; 12 to less than 18 years, 5.8%; 18 years or older, 2.2%). Among AD prev (n = 94,483), mild, moderate, and severe AD comprised 57.7%, 36.2%, and 6.1% (adults 43.8%, 46.3%, 9.9%), respectively. Dermatologist and allergist visits and hospitalization rates (at least one) were 40.7%, 6.6%, and 3.8% in 2017. Compared with controls, overall and moderate-to-severe AD were associated with 36% and 52% increases in annual per-person costs (incremental costs $126 and $190)., Conclusions: AD epidemiology in Israel is comparable with other real-world database studies. AD imposes an economic burden that increases with disease severity., (© 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Despite recent advances in understanding the immunopathogenesis of oral lichen planus (LP), the initial triggers of lesion formation and the essential pathogenic pathways are unknown. It is therefore not surprising that the clinical management of oral LP poses considerable difficulties to the dermatologist and the oral physician. A consensus meeting was held in France in March 2003 to discuss the most controversial aspects of oral LP. Part 1 of the meeting report focused on (1) the relationship between oral LP and viral infection, with special emphasis on hepatitis C virus (HCV), and (2) oral LP pathogenesis, in particular the immune mechanisms resulting in lymphocyte infiltration and keratinocyte apoptosis. Part 2 focuses on patient management and therapeutic approaches and includes discussion on malignant transformation of oral LP.

Despite recent advances in understanding the immunopathogenesis of oral lichen planus (LP), the initial triggers of lesion formation and the essential pathogenic pathways are unknown. It is therefore not surprising that the clinical management of oral LP poses considerable difficulties to the dermatologist and the oral physician. A consensus meeting was held in France in March 2003 to discuss the most controversial aspects of oral LP. Part 1 of the meeting report focuses on (1) the relationship between oral LP and viral infection with special emphasis on hepatitis C virus (HCV), and (2) oral LP pathogenesis, in particular the immune mechanisms resulting in lymphocyte infiltration and keratinocyte apoptosis. Part 2 focuses on patient management and therapeutic approaches and includes discussion on malignant transformation of oral LP.

The kinetics of gene expression associated with the development of cutaneous graft-versus-host disease (GVHD) were examined in a mouse model of MHC-matched allogeneic hematopoietic stem cell transplantation. Ear skin was obtained from recipient mice with or without GVHD between 7 and 40 days after transplantation for histopathological analysis and gene expression profiling. Gene expression patterns were consistent with early infiltration and activation of CD8(+) T and mast cells, followed by CD4(+) T, natural killer, and myeloid cells. The sequential infiltration and activation of effector cells correlated with the histopathological development of cutaneous GVHD and was accompanied by up-regulated expression of many chemokines and their receptors (CXCL-1, -2, -9, and -10; CCL-2, -5, -6, -7, -8, -9, -11, and -19; CCR-1 and CCR-5), adhesion molecules (ICAM-1, CD18, Ly69, PSGL-1, VCAM-1), molecules involved in antigen processing and presentation (TAP1 and TAP2, MHC class I and II, CD80), regulators of apoptosis (granzyme B, caspase 7, Bak1, Bax, and BclII), interferon-inducible genes (STAT1, IRF-1, IIGP, GTPI, IGTP, Ifi202A), stimulators of fibroblast proliferation and matrix synthesis (interleukin-1beta, transforming growth factor-beta1), and markers of keratinocyte proliferation (keratins 5 and 6), and differentiation (small proline-rich proteins 2E and 1B). Many acute-phase proteins were up-regulated early in murine cutaneous GVHD including serum amyloid A2 (SAA2), SAA3, serpins a3g and a3n, secretory leukocyte protease inhibitor, and metallothioneins 1 and 2. The kinetics of gene expression were consistent with the evolution of cutaneous pathology as well as with current models of disease progression during cutaneous GVHD.

Background: Cell-mediated immune responses in oral lichen planus (OLP) may be regulated by cytokines and their receptors., Methods: In situ cytokine expression and in vitro cytokine secretion in OLP were determined by immunohistochemistry and ELISA., Results: The majority of subepithelial and intraepithelial mononuclear cells in OLP were CD8+. In some cases, intraepithelial CD8+ cells were adjacent to degenerating keratinocytes. CD4+ cells were observed mainly in the deep lamina propria with occasional CD4+ cells close to basal keratinocytes. Mononuclear cells expressed IFN-gamma in the superficial lamina propria and TNF-alpha adjacent to basal keratinocytes. Basal keratinocytes expressed TNF-alpha as a continuous band. TNF R1 was expressed by mononuclear cells and basal and suprabasal keratinocytes. There was variable expression of TGF-beta1 in the subepithelial infiltrate while all intraepithelial mononuclear cells were TGF-beta1-. Keratinocytes in OLP stained weakly for TGF-beta1. Unstimulated OLP lesional T cells secreted IFN-gamma in vitro. TNF-alpha stimulation down-regulated IFN-gamma secretion and up-regulated TNF-alpha secretion. IL-4, IL-10 and TGF-beta1 secretion were not detected., Conclusions: These data suggest the development of a T helper 1 immune response that may promote CD8+ cytotoxic T-cell activity in OLP.

Cytokines produced by T-cells in periodontal lesions may determine the nature of the adaptive immune response. Since different antigen-presenting cells (APC) may direct the Th1/Th2 response, P. gingivalis-specific T-cell lines were established by different APC subpopulations, and their cytokine profiles were determined. Peripheral blood mononuclear cells induced similar percentages of IL-4+ and IFN-gamma+ T-cells and lower percentages of IL-10+ T-cells. Epstein-Barr virus-transformed B-cells (LCL) induced higher percentages of IL-4+ cells than IFN-gamma+ cells, with lower percentages of IL-10+ cells. Peripheral blood mononuclear cells induced a higher percent of IFN-gamma+ CD8 cells than LCL (p = 0.004). Purified B-cells, monocytes, and dendritic cells induced similar percentages of IL-4+ and IFN-gamma+ cells, although again, the percentage of IL-10+ cells was lower. The results of the present study have demonstrated that, as measured by FACS analysis of intracytoplasmic cytokines, P. gingivalis-specific T-cells produce both Th1 and Th2 cytokines, regardless of the APC population.

Lichen planus is a disorder characterized by lesions of the skin and oral mucous membranes. Although many patients have involvement of both skin and oral mucosa at some stage during the progress of the disease, a larger group has oral involvement alone. It has been reported that oral lichen planus (OLP) affects one to two percent of the general population and has the potential for malignant transformation in some cases (1, 2). Like many chronic inflammatory skin diseases, it often persists for many years. Numerous disorders may be associated with OLP such as graft-vs.-host disease and Hepatitis C virus infection (3), however, it is unclear how such diverse influences elicit the disease and indeed whether they are identical to idiopathic OLP. Available evidence supports the view that OLP is a cell-mediated immunological response to an induced antigenic change in the mucosa (4-6). Studies of the immunopathogenesis of OLP aim to provide specific novel treatments as well as contributing to our understanding of other cell-mediated inflammatory diseases. In this paper, the interactions between mast cells and T cells are explored from the standpoint of immune regulation. From these data, a unifying hypothesis for the immunopathogenesis of OLP is then developed and presented.

Background: T lymphocytes and mast cells infiltrate the lamina propria in oral lichen planus (OLP). Chemokines and their receptors are involved in T cell and mast cell migration and accumulation during the inflammatory process., Methods: In the present study, we investigated the role of RANTES and its receptors in OLP using immunohistochemistry, RT-PCR and an in vitro chemotaxis assay., Results: RANTES and CCR1 were expressed on T cells and mast cells in OLP, while OLP lesional T cell supernatants stimulated CCR1 mRNA expression in a human leukemia mast cell line (HMC-1). TNF-alpha stimulated CCR1, CCR4 and CCR5 mRNA expression in the same cell line. OLP lesional T cell supernatants stimulated HMC-1 migration, which was partly inhibited by anti-RANTES antibody., Conclusions: The present study shows, for the first time, the distribution of RANTES and CCR1 in OLP. It is hypothesized that RANTES and CCR1 may play important roles in mast cell trafficking and related events in OLP.

Both antigen-specific and non-specific mechanisms may be involved in the pathogenesis of oral lichen planus (OLP). Antigen-specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen-specific keratinocyte killing by CD8(+) cytotoxic T-cells. Non-specific mechanisms include mast cell degranulation and matrix metalloproteinase (MMP) activation in OLP lesions. These mechanisms may combine to cause T-cell accumulation in the superficial lamina propria, basement membrane disruption, intra-epithelial T-cell migration, and keratinocyte apoptosis in OLP. OLP chronicity may be due, in part, to deficient antigen-specific TGF-beta1-mediated immunosuppression. The normal oral mucosa may be an immune privileged site (similar to the eye, testis, and placenta), and breakdown of immune privilege could result in OLP and possibly other autoimmune oral mucosal diseases. Recent findings in mucocutaneous graft-versus-host disease, a clinical and histological correlate of lichen planus, suggest the involvement of TNF-alpha, CD40, Fas, MMPs, and mast cell degranulation in disease pathogenesis. Potential roles for oral Langerhans cells and the regional lymphatics in OLP lesion formation and chronicity are discussed. Carcinogenesis in OLP may be regulated by the integrated signal from various tumor inhibitors (TGF-beta 1, TNF-alpha, IFN-gamma, IL-12) and promoters (MIF, MMP-9). We present our recent data implicating antigen-specific and non-specific mechanisms in the pathogenesis of OLP and propose a unifying hypothesis suggesting that both may be involved in lesion development. The initial event in OLP lesion formation and the factors that determine OLP susceptibility are unknown.

Background: We investigated basement membrane (BM) disruption and the distribution of mast cells (MCs) and T cell subsets, in oral lichen planus (OLP) and normal buccal mucosa (NBM) using immunohistochemistry. In OLP, there were increased numbers of tryptase+ MCs in areas of BM disruption (P < 0.05)., Method: We identified clusters of intraepithelial CD8+ T cells in OLP, specifically in regions of BM disruption. The number of intraepithelial CD8+ T cells in regions of BM disruption was significantly greater than in regions of BM continuity (P < 0.05)., Results: There were comparable numbers of lamina propria CD8+ T cells in regions of BM disruption and BM continuity. The number of CD4+ T cells in the epithelium and lamina propria of OLP lesions did not vary between regions of BM disruption and BM continuity., Conclusion: These data suggest a role for MCs in epithelial BM disruption in OLP. CD8+ T cells may migrate through BM breaks to enter the OLP epithelium.

Cell-surface proteoglycans are involved in lymphocyte migration and activation. This study investigated the expression of syndecan-1, syndecan-4, and glypican in peripheral blood lymphocytes and by lymphocytes in variously inflamed periodontal tissues. Gingival specimens from healthy, gingivitis, or chronic periodontitis sites were stained by means of antibodies against B- and T-lymphocytes and also syndecan-1, syndecan-4, and glypican. Syndecan-1 expression by peripheral blood mononuclear cells (PBMC) from healthy, gingivitis, and chronic periodontitis subjects was assessed by flow cytometry. Syndecan-1 was expressed by B-cells/plasma cells but not T-cells in both gingivitis and chronic periodontitis lesions. Both B-cells/plasma cells and T-cells in gingivitis and chronic periodontitis expressed syndecan-4. Glypican was expressed only by macrophages. Stimulation of PBMC with mitogens and growth factors modulated syndecan-1 expression in both the T- and B-cells. Thus, cell-surface proteoglycan expression by lymphocytes in periodontal inflammation is cell-type-specific and may be modulated by inflammation.

Mast cells are important effector cells of the immune system. We describe a rapid and inexpensive microassay to determine histamine release from human gingival mast cells. The assay is based on the coupling of histamine with o-phthalaldehyde (OPT) at a highly alkaline pH to form a fluorescent product. Using this assay with a sample volume of 10 microl/well in a 384 black well microplate, the histamine detection limit was 0.031 microg/ml. The human mast cell line (HMC-1) and fresh mast cells isolated from human gingival tissue (n = 10) were stimulated with substance P, anti-IgE or calcium ionophore A23187. Calcium ionophore significantly increased histamine release from HMC-1 cells and gingival mast cells (p < 0.05). This microassay will facilitate the study of mast cell histamine release in diseased oral mucosa.

Background: Oral lichen planus (OLP) is characterized by a sub-epithelial lymphocytic infiltrate, basement membrane (BM) disruption, intra-epithelial T-cell migration and apoptosis of basal keratinocytes. BM damage and T-cell migration in OLP may be mediated by matrix metalloproteinases (MMPs)., Methods: We examined the distribution, activation and cellular sources of MMPs and their inhibitors (TIMPs) in OLP using immunohistochemistry, ELISA, RT-PCR and zymography., Results: MMP-2 and -3 were present in the epithelium while MMP-9 was associated with the inflammatory infiltrate. MMP-9 and TIMP-1 secretion by OLP lesional T cells was greater than OLP patient (p < 0.01) and healthy control subject (p < 0.001) peripheral blood T cells. MMP-9 and TIMP-1 mRNA levels were greater in OLP lesional T cells compared with healthy control subject peripheral blood T cells p < 0.01). Tumor necrosis factor (TNF)-alpha upregulated OLP lesional T-cell MMP-9 (not TIMP-1) mRNA and secretion (p < 0.05). The in vitro activation rate of MMP-9 from OLP lesional T cells was greater than that from OLP peripheral blood T cells (p < 0.05)., Conclusion: T-cell-derived MMP-9 may be involved in the pathogenesis of OLP. Relative over-expression of MMP-9 (compared with TIMP-1) may cause BM disruption and facilitate intra-epithelial T-cell migration in OLP.

The anterior lingual salivary glands (glands of Blandin and Nuhn) are mixed mucous and serous glands that are embedded within the musculature of the anterior tongue ventrum. Five cases of mucocele of the glands of Blandin and Nuhn are presented. These mucoceles on the anterior tongue ventrum were exophytic and resembled pyogenic granulomata, polyps, or squamous papillomata. In 2 cases, the onset of the mucocele was associated with trauma to the anterior tongue. All cases were mucus extravasation phenomena. A history of trauma and recovery of mucus with fine needle aspiration are helpful in the clinical diagnosis of mucocele of the glands of Blandin and Nuhn, as are the following characteristics of the mucocele: rapid onset, increase and reduction in size, bluish color, and fluid-filled consistency. During surgery, the glands that are deep in the tongue musculature are commonly left behind, resulting in persistence of the lesion. Careful clinical evaluation of these lesions and preoperative awareness of the surgical anatomy of the glands of Blandin and Nuhn may minimize the need for repeated surgical procedures.

We examined the in vitro cytotoxic activity of cutaneous T-cell lines and clones from lichen planus (LP) patients against autologous epidermal keratinocytes. T cells were cultured from LP lesions and adjacent clinically normal skin and cloned by limiting dilution. Keratinocytes were cultured from LP lesions and adjacent clinically normal skin and immortalized by transfection with the E6 and E7 genes from human papillomavirus 16 (HPV16). The lesional T-cell line from one LP patient contained 27% gammadelta+ T cells and was significantly more cytotoxic against autologous lesional keratinocytes than the T-cell line from clinically normal skin. Clones isolated from the lesional T-cell line were significantly more cytotoxic against autologous lesional keratinocytes than clones isolated from the non-lesional T-cell line. Most cytotoxic clones from LP lesions were CD8+ and most non-cytotoxic clones from LP lesions were CD4+. One cytotoxic clone was CD4- and CD8- and expressed the gammadelta T-cell receptor. Two CD8+ LP lesional T-cell clones showed dose-dependent killing of HPV16 E6/E7-immortalized autologous lesional and normal keratinocytes, but no cytotoxic activity against Epstein-Barr virus-transformed autologous B-cell blasts. The cytotoxic activity of CD8+ lesional T-cell clones against autologous lesional keratinocytes was partially blocked with anti-major histocompatibility complex (MHC) class I monoclonal antibodies. These data support the hypothesis that CD8+ lesional T cells recognize an antigen associated with MHC class I on lesional keratinocytes and that CD8+ cytotoxic T cells lyse keratinocytes in LP lesions.

The function of human epidermal T cells (ETC) is unknown. In the present study, dermal T cells (DTC), ETC and keratinocytes were cultured from normal human skin. DTC and ETC lines were expanded in medium containing interleukin 2. The autologous keratinocytes were transfected with a human papillomavirus 16 E6 and E7 plasmid to produce an immortal keratinocyte line "HEK001". Lymphocyte migration and adhesion to HEK001 was assessed in calcein fluorimetric assays. ETC migrated towards HEK001 three to four times more than DTC. ETC adhered to HEK001 two to four times more than DTC. The proportion of ETC expressing the cutaneous lymphocyte-associated antigen was greater than that of DTC (26% and 1%, respectively). The keratinocyte line HEK001 expressed ICAM-1 following stimulation with TNF-alpha or IFN-gamma and following coculture with autologous cutaneous T cells. A blocking anti-ICAM-1 antibody reduced DTC and ETC adhesion to HEK001 by 30% and 50%, respectively. Therefore, cutaneous T cells may upregulate keratinocyte ICAM-1 expression which mediates adhesion to autologous keratinocytes. These results are consistent with the hypothesis that the ETC and DTC populations are distinct. Both directed migration (epidermotropism) and selective retention may be involved in the development and maintenance of the ETC population in normal human skin.

Enamel-producing cells (ameloblasts) pass through several phenotypic and functional stages during enamel formation. In the transition between secretory and maturation stages, about one quarter of the ameloblasts suddenly undergo apoptosis. We have studied this phenomenon using the continuously erupting rat incisor model. A special feature of this model is that all stages of ameloblast differentiation are presented within a single longitudinal section of the developing tooth. This permits investigation of the temporal sequence of gene and growth factor receptor expression during ameloblast differentiation and apoptosis. We describe the light and electron microscopic morphology of ameloblast apoptosis and the pattern of insulin-like growth factor-1 receptor expression by ameloblasts in the continuously erupting rat incisor model. In the developing rat incisor, ameloblast apoptosis is associated with downregulated expression of the insulin-like growth factor-1 receptor. These data are consistent with the hypothesis that ameloblasts are "hard wired" for apoptosis and that insulin-like growth factor-1 receptor expression is required to block the default apoptotic pathway. Possible mechanisms of insulin-like growth factor-1 inhibition of ameloblast apoptosis are presented. The rat incisor model may be useful in studies of physiological apoptosis as it presents apoptosis in a predictable pattern in adult tissues.

Over 750 new intra-oral squamous cell carcinomas are registered in Australia each year. In this article, the authors review the epidemiology, aetiology, genetics and spread of intra-oral squamous cell carcinoma. The mechanisms of field cancerization are discussed. The prevention of intra-oral squamous cell carcinoma is highlighted and future treatments are presented.

In the present study, MRNA for the cytokines interleukin-2 (IL-2), IL-4, IL-10 tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor beta-1 (TGF-beta-1) were investigated in oral lichen planus (OLP) lesions using in situ hybridization with 35S-labelled oligonucleotide probes on frozen tissue sections. In addition, the expression of interferon-gamma (IFN-gamma), IL-10 and IL-4 mRNAs was analysed in cultured lesional T lymphocytes from oral lichen planus by polymerase chain reaction. Cells expressing mRNA for IL-2, IL-4, IL-10, TNF-alpha and TGF-beta 1 were found in all the biopsies studied. Approximately 1-2% of the total number of infiltrating cells in the lesions were positive for each of the different cytokine mRNAs. Most biopsies contained basement membrane-oriented, mRNA-positive cells. In the cultured T-cell lines, message for IFN-gamma was detected in all the patients, IL-10 in all but one, and IL-4 in just one of the seven patients investigated. The results suggest that mRNA for both pro- and anti-inflammatory cytokines, i.e., mixed T-helper 1 (TH1) and TH2 cytokine profiles, are generated simultaneously by a limited number of cells in chronic lesions of OLP.

Objective: To study the change of suppressor T-cell function in patients with RAU., Methods: Samples of 12 patients with RAU active phase were studied by it suppressor assay., Results: The T-cell suppress rates at ConA 1,2,4 and 8 mg/L were 60%, 40%, 27% and 20% respectively, and were evidently lower when compared with normal controls' 72%, 56%, 41% and 34% (P < 0.05)., Conclusion: The suppressor T-cell function may be depressed in RAU patients.

Unlabelled: To study V beta gene expression in oral lichen planus (OLP) lesional T lymphocytes cell lines., Materials and Methods: Lesional T lymphocytes were isolated from eight OLP patients and cell lines established. The total RNA was extracted from these lymphocyte cell lines and reverse transcribed. cDNA was amplified by the polymerase chain reaction (PCR) using a panel of 26 V beta-specific oligonucleotide primers followed by qualitative analysis of the electrophoresed reaction products., Results: V beta 1, 2, 3, 5.1, 6.1-3, 7, 8, 9, 22, 23, and 24 were represented consistently in all of the OLP samples, V beta 11, 12, and 17 were consistently negative, while the other V beta families (V beta 4, 5.2-3, 10, 13.1, 13.2, 14, 15, 16, 18, 19, 20, and 21) were variable. V beta 22 and 23 were the most strongly expressed in all patients., Conclusions: A limited T cell receptor (TCR) gene usage indicates a degree of oligoclonality within these lesional T lymphocyte cell lines from OLP. This implies that OLP may be an antigen-specific disease or linked to a limited number of superantigens.

Exfoliative cytology is a rapid, non-invasive procedure for assessing dysplastic change within the oral epithelium. The indications for oral exfoliative cytology are reviewed and a technique for cell collection and smear examination is presented. The value of exfoliative cytology in oral cancer screening programmes as a public health measure is discussed.

Smears of buccal mucosa, dorsal surface of the tongue and floor of mouth were taken from 10 patients with histologically confirmed oral lichen planus and 12 healthy age- and sex-matched controls. In buccal smears, no significant differences in cytoplasmic and nuclear areas were observed between lesional, adjacent non-lesional and control tissues. However, the cytoplasmic area in smears from lichen planus lesions on the dorsum of the tongue and adjacent clinically normal mucosa was reduced compared with healthy controls. The cytoplasmic: nuclear ratio in smears from clinically normal floor of mouth in oral lichen planus was similarly reduced. Papanicolaou-stained smears from buccal lichen planus showed increased keratinization compared with normal buccal mucosa. These findings demonstrate that quantitative cytology can detect both cytoplasmic and nuclear changes in oral lichen planus.

Mutation, deactivation and disregulated expression of oncogenes and tumour-suppressor genes may be involved in the pathogenesis of oral squamous cell carcinoma (SCC). Deactivation of the p53 tumour-suppressor gene allows cell proliferation and blocks apoptosis of malignant oral keratinocytes. Mutation in the ras oncogene results in persistent mitogenic signalling. Upregulatioed c-Myc expression, in the presence of growth factors, provides an additional proliferative signal. Loss of retinoblastoma tumour-suppressor gene (Rb) function may contribute to oral keratinocyte hyperproliferation and recent evidence suggests that simultaneous deactivation of both p53 and Rb is required for tumourigenesis. Enhanced Bcl-2 and reduced Fas expression inhibit tumour cell apoptosis and may convey resistance to cytotoxic drugs and T cell-mediated cytotoxicity, respectively. Exogenous mutagens such as tobacco, alcohol and viral oncogenes may cause altered expression of oncogenes and tumour-suppressor genes in some cases of oral SCC. The impact of these mechanisms on future therapies for oral SCC is highlighted.

Heat shock protein (HSP) expression is upregulated in tumour cells and, therefore, HSP expression is a likely marker of the malignant potential of oral epithelial lesions. Furthermore, the 70-kDa HSP (HSP 70) is implicated in the degree of tumour differentiation, the rate of tumour proliferation and the magnitude of the anti-tumour immune response. Accordingly, the distribution and intensity of HSP 70 expression was assessed in the epithelial compartment of oral squamous cell carcinoma (SCC, n = 29), dysplastic oral epithelium (n = 18) and benign oral mucosal lesions (n = 22) using avidin-biotin complex immunohistochemistry and microdensitometry under standardised conditions. Staining intensity was recorded in kilo-ohms (k omega). Normal oral mucosa (n = 15) was used for comparison, and results were analysed using Kruskall-Wallis and Fisher's exact tests. The distribution of HSP 70 expression in well differentiated SCC was significantly different from that in poorly differentiated SCC (P < 0.05), the latter demonstrating a more focal staining pattern. Median staining intensity in SCC (6.22 k omega), epithelial dysplasia (9.61 k omega) and the benign oral mucosal lesions (8.28 k omega) was significantly greater than that in normal oral mucosa (5.64 k omega; P < 0.05). Staining intensity in poorly differentiated SCC (7.66 k omega) was greater than that in moderately differentiated SCC (4.77 k omega), although this result just failed to reach statistical significance (P = 0.06). These results suggest that, as employed currently, HSP 70 expression is not a definitive marker of oral malignancy or malignant potential.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the potential role of heat shock protein (HSP) in the pathogenesis of oral lichen planus (OLP), sections of OLP, normal oral mucosa, non-specific oral ulceration (NSOU) and dysplastic OLP were assessed for HSP expression using avidin-biotin complex immunohistochemistry with an anti-HSP 70 polyclonal antibody. There were statistically significant differences in both the vertical and horizontal staining distribution when other groups were compared with the OLP group (p < 0.01). Using microdensitometry, the mean staining intensity in OLP, dysplastic OLP and NSOU was elevated in comparison with normal oral mucosa (p < 0.001). In a standard tritiated thymidine uptake assay, lymphocytes extracted from nine OLP lesions demonstrated significant proliferation when stimulated with purified protein derivative (PPD), of which HSP is a major constituent, with stimulation indices ranging from 2 to 132. These results are consistent with the hypothesis that, in OLP patients, diverse exogenous agents may cause upregulated expression of HSP by oral mucosal keratinocytes. A reaction of cytotoxic T lymphocytes to these activated keratinocytes may then result in the tissue destruction which is characteristic of OLP lesions.

Lymphocytes were extracted from six biopsy specimens of oral lichen planus. T-lymphocyte lines were expanded in culture with phytohaemagglutinin and interleukin 2, and cloned by limiting dilution. Fifteen T-cell clones were isolated with a probability of clonality of 96.3%. The majority of clones (n = 13) expressed the alpha beta T-cell receptor, and of these, 11 were CD8+ and two were CD4+. Two clones were CD4- and CD8-, and expressed the gamma delta T-cell receptor. The ability of these clones (effectors) to suppress concanavalin-A-stimulated proliferation of autologous lesional T-cell lines (responders) was assessed. Maximum suppressor activity ranged from 17 to 100%. The majority of clones (n = 12), including a CD3+ CD4+ CD8-alpha beta+ clone, displayed suppressor activity which was proportional to the effector to responder ratio. A CD3+CD4+CD8-alpha beta+ clone and a CD3+CD4-CD8-gamma delta+ clone displayed substantial helper activity at higher effector to responder ratios. These results demonstrate differential helper and suppressor activity of T-lymphocyte clones extracted from oral lichen planus lesions. The balance between help and suppression may be a fundamental determinant of immunological activity within the lymphocytic infiltrate of oral lichen planus, and hence may dictate the clinical behaviour of the disease.

Lymphocytes were extracted from 11 biopsy specimens of oral lichen planus (OLP) by collagenase digestion, and cell lines were expanded with repetitive cycles of stimulation (with phytohaemagglutinin) and rest in media supplemented with interleukin 2. Four OLP lines contained a majority of CD3+CD4-CD8+ cells, in six lines the CD4:CD8 ratio was between 1 and 2, and in one line the CD4:CD8 ratio was 5:1. Limiting dilution of nine lines at 0.3 and 1.0 cells/well resulted in viable wells (putative clones) with plating efficiencies ranging from 0.0 to 18.1 percent and 0.0 to 22.2 percent respectively. The majority of clones were CD3+CD4-CD8+alpha beta+gamma delta-, although three clones were CD3+CD4+CD8-alpha beta+gamma delta- and one clone was CD3+CD4-CD8- and expressed the gamma delta T cell receptor. T cell clones derived from lymphocytes extracted from OLP lesions may be generated and maintained in culture providing opportunity for their further phenotypic and functional characterisation. This strategy may facilitate the identification of a putative oral lichen planus-specific antigen and indicate the frequency of lichen planus-specific T cells within lesions of OLP.

Current evidence for the involvement of cell-mediated immunological mechanisms in the pathogenesis of oral lichen planus is reviewed. Both a spatial and temporal relationship between cytotoxic T Lymphocytes and epithelial damage have been reported. Although keratinocytes appear to be the target for destruction in oral lichen planus, their role in antigen presentation is unclear. We propose that in oral lichen planus patients, diverse exogenous agents such as drugs, trauma and infection, stimulate the expression of a common self molecule by oral mucosal keratinocytes. An autoimmune reaction by cytotoxic T lymphocytes to these activated keratinocytes may result in the tissue destruction which is characteristic of oral lichen planus.

Oral lichen planus (OLP) is a common inflammatory condition of the oral mucous membranes which affects between one and two percent of the general population. In accordance with the protracted clinical course of OLP and its association with known auto-immune diseases, the level of self-tolerance is questionable and possibly diminished in patients with this disorder. Normal suppressor T lymphocyte function is reputedly an essential element in the maintenance of self-tolerance, and deficient cell-mediated suppressor activity is implicated in the pathogenesis of auto-immune diseases. For assessment of in vitro cell-mediated suppressor activity in OLP, peripheral blood mononuclear cells (PBMC) from ten patients with OLP and from 11 control subjects were activated with the plant mitogen concanavalin A (Con A), followed by co-culture with autologous responder cells. The ability of irradiated Con A-activated cells to suppress the proliferation of Con A-stimulated responder cells was determined. Con A-induced suppressor activity of PBMC in the OLP patients was significantly less than that in control subjects (p = 0.001). Results of the present investigation complement previous in vitro findings which provided indirect evidence of deficient cell-mediated suppressor activity in OLP, particularly a decreased proportion of circulating CD4+CD45RA+ lymphocytes and reduced Con A-stimulated PBMC proliferation. The depressed Con A-induced suppressor activity of PBMC in the OLP patients provides direct evidence of deficient in vitro cell-mediated suppressor function in OLP, and suggests that defective cell-mediated suppressor circuits and reduced self-tolerance may be involved in the pathogenesis of this disorder.

To assess cellular immunity in oral lichen planus (OLP), peripheral blood mononuclear cells (PBMC) were obtained from 19 OLP patients and 30 control subjects. The proportions of circulating CD45RA+ and CD29+ lymphocyte subsets were determined. The proliferative activity of PBMC to the non-specific plant mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) was examined together with the spontaneous proliferative response and the response in the autologous mixed lymphocyte reaction (AMLR). In the OLP group, the proportion of CD4+ CD45RA+ T lymphocytes was significantly less than control subjects and the proportion of CD4+ CD29+ T lymphocytes was increased significantly. The proliferative response to PHA was similar in OLP and controls subjects. Con A-stimulated PBMC proliferation was decreased significantly in the OLP group. Spontaneous PBMC proliferation in patients with non-reticular lesions was significantly less than control subjects. Despite a mildly depressed response in the AMLR in OLP patients, this result was not statistically significant. Results of the phenotypic analysis of peripheral blood lymphocytes indicate a decreased proportion of naive T cells and an increased proportion of primed memory T cells, although the antigen specificity of these memory cells remains to be determined. Results of the functional assays would seem to reflect this phenotypic shift, and as T cells responding to Con A stimulation and in the AMLR possess suppressor-inducer activity, these results may also suggest an association between OLP and defective innate T cell-mediated suppressor circuits.