In reply to the short communication "Malignant transformation of oral lichen planus" by A. Larsson and G. Warfvinge in Oral Oncology 39 (2003) 630-1.
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Biopsy↗
Biomedical subjects
M Jontell
Publications and source records attributed to M Jontell.
T-cell costimulatory capacity of oral and skin epithelial cells in vitro: presence of suppressive activity in supernatants from skin epithelial cell cultures.
Oral Langerhans cells (LC) have better T-cell costimulatory capacity than skin LC. In this study factors affecting this capacity have been assessed in a mixed epithelial cell lymphocyte reaction (MELR) assay. Flow cytometry analysis of freshly recovered cells revealed major histocompatibility complex (MHC) class II molecule expression on 7.5% of the oral epithelial cells and 9.7% of the skin epithelial cells. Monoclonal anti class II antibodies significantly reduced the T-cell proliferation in the MELR. Pretreatment of skin epithelial cells with interleukin-1beta, tumour necrosis factor-alpha or interferon (IFN)-gamma did not affect the MELR proliferation, but incubation with IFNgamma significantly suppressed the T-cell response. Transfer of supernatants from cultures of skin epithelial cells and allogeneic T cells to cultures of oral epithelial cells and T cells resulted in a reduced T-cell proliferation while supernatants from oral epithelial cells and T cells did not reduce proliferation. The higher proliferation in cultures of T cells and oral epithelial cells than in cultures containing skin epithelial cells may be due to the presence of a suppressive factor in the skin epithelial cell suspensions.
Animals↗
Langerhans cells from human oral epithelium are more effective at stimulating allogeneic T cells in vitro than Langerhans cells from skin.
This report is focused on the functional capacity of Langerhans cells (LC) in the epithelium of skin and oral mucosa, which both meet different antigenic challenges. The capacity of LC from human oral and skin epithelium to provide co-stimulatory signals to T cells in vitro was compared. LC in a crude suspension of oral epithelial cells had a significantly enhanced T cell co-stimulatory capacity compared to skin epithelial cells. This applied both to cultures with concanavalin A (con-A)-stimulated syngeneic T cells and to a mixed epithelial cell lymphocyte reaction involving allogeneic T cells. The co-stimulatory capacity of oral and skin epithelial cells was reduced by >70% if monoclonal antibodies against HLA-DR, -DP and -DQ were added to the cultures with allogeneic T cells, indicating the involvement of HLA class II expressing LC. Immunohistochemistry revealed that 6% of the epithelial cells were CD1a + LC in sections from both oral and skin epithelium. Interleukin (IL)-8 production was higher in cultures of oral epithelial cells and con-A stimulated T cells than in corresponding cultures with skin epithelial cells as accessory cells. The results suggest that LC in human oral epithelium are more efficient at stimulating T cells than those of skin.
Adult↗
Oral and intestinal microflora in 5-fluorouracil treated rats, translocation to cervical and mesenteric lymph nodes and effects of probiotic bacteria.
Serious systemic infections may occur during cancer chemotherapy due to disturbances in the oropharyngeal and gastrointestinal microflora, impaired mucosal barrier functions and immunosuppression. Bacteria may spread from the gastrointestinal tract to the regional lymph nodes. The routes for bacterial spread from the oral cavity are less well known. In the present study we investigated changes in the oral and intestinal microfloras in rats given 50 mg/kg 5-fluorouracil (5-FU) i.v. for 6 days. Bacterial dissemination to the lymph nodes draining the oral cavity and the lymph nodes draining the gastrointestinal tract was examined. Effects of adding the probiotic strain Lactobacillus plantarum 299v in the drinking water to the rats were measured. 5-FU treatment caused an increase in the number of facultative and strictly anaerobic bacteria in biopsies from the oral cavity and an increase in the number of facultative anaerobes in the large intestine. The proportion of facultative gram-negative rods increased in both the oral cavity and intestine. Bacteria translocated to both the cervical and mesenteric lymph nodes in untreated animals and increased in numbers after 5-FU treatment due to an increase in the number of facultative gram-negative rods. Treatment with L. plantarum 299v improved food intake and body weight in 5-FU-treated rats. It also reduced the 5-FU-induced raise in the total numbers of facultative anaerobes in the intestine, but did not reduce translocation and did not prevent diarrhea. This study reinforces the oral cavity, along with the gastrointestinal tract, as a source for bacterial dissemination. The use of probiotic bacteria may reduce some side effects of 5-FU treatment.
Animals↗
5-Fluorouracil induces autophagic degeneration in rat oral keratinocytes.
In this study, we investigated the effect of 5-fluorouracil (5-FU) on the keratinocytes of oral epithelium. Female Lewis rats were given 5-FU i.v. and were killed 12, 24 or 36 h after injection. The buccal mucosa was dissected. The number of nuclei with DNA strand breaks and the total number of nuclei per volume of the epithelial basal cell layer was estimated using terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling. Epithelial cells were analysed by flow cytometry, transmission electron microscopy and a dye exclusion test. The number of cells with DNA strand breaks increased in 5-FU treated rats. Flow cytometry showed a decrease in cell size and an increase in granularity with increasing doses of 5-FU. Dye exclusion gave no indication of degenerate cell membranes. By transmission electron microscopy, the cells showed evidence of degeneration, shrinkage and loss of cell-to-cell contact. Vacuolation was extensive and, in contrast to apoptotic cells, nuclear chromatin condensation seemed to occur centrally in the nuclei. The results show that 5-FU treatment in vivo induces alterations in rat oral keratinocytes that are consistent with autophagic degeneration.
Animals↗
Erosive oral lichen planus and salivary cortisol.
Patients with oral lichen planus (OLP) often relate the onset and aggravation of oral symptoms to increased levels of stress. Under normal conditions, stress induces increased cortisol secretion that counteracts inflammatory reactions. The objective of the present study was to assess whether patients with OLP have an impaired capacity to elevate their cortisol concentrations as a response to stress. Saliva samples were collected for cortisol analysis from 10 OLP patients once every 15 min during a 2-h test period. In order to induce stress during a part of this test period, the patients were confronted with a computerised device specifically developed for the induction of transient stress. A visual analogue scale (VAS) and a mood adjective check list (MACL) were used to estimate the degree of permanent stress. A control group of patients was matched for age and sex. The OLP patients did not present with different stress scores when a psychometric test (MACL) was used. No statistically significant correlation between cortisol concentration and stress level was observed. Thus, no support for an impaired capacity of OLP patients to suppress an immune response through cortisol induction in conjunction with experimental stress was revealed.
Adult↗
Effects of 5-fluorouracil on mitogen-induced costimulatory capacity of accessory cells from rat oral mucosa and dental pulp.
The present study was designed to investigate the effect of the antimetabolite 5-fluorouracil (5-FU) on the capacity of the oral epithelium and the dental pulp to induce a mitogen-driven T-cell proliferation. Inbred Lewis rats were given 6 i.v. injections of 5-FU (30 mg/kg or 50 mg/kg) over a period of 8 days. Suspensions of oral epithelial and dental pulpal cells were prepared. The costimulatory capacity of the accessory cells from treated animals was monitored by their ability to induce a mitogen (ConA)-mediated proliferation of T cells isolated from regional lymph nodes of untreated animals. Accessory epithelial cells from rats treated with the high dose of 5-FU, but not the low dose, induced a decreased T-cell proliferation compared to controls. Accessory pulpal cells from rats, treated with 30 mg/kg or 50 mg/kg of 5-FU, induced a lower T-cell proliferation. When MHC class II molecule depleted T-cell suspensions from lymph nodes of 5-FU-injected animals were incubated with ConA, a significant proliferative response was observed. This finding correlated with an increase of MHC class II molecule expressing cells detected after incubation, although no such cells were observed immediately following the initial purification step of T cells. This finding demonstrates that the accessory cells could partly restore their expression of MHC class II molecules during incubation. The results of the study suggest that the function of immunocompetent cells of the oral mucosa and dental pulp is influenced by treatment with 5-FU and that the function of accessory cells of the pulp is affected more than the function of accessory cells derived from the oral mucosa.
Animals↗
Langerhans cells and T cells in oral graft versus host disease and oral lichen planus.
Chronic graft versus host disease (cGVHD) of the oral mucosa, following allogeneic stem cell transplantation, and oral lichen planus (OLP) are both mucosal diseases where the immune system is involved in the pathogenesis. Although the aetiology of the two conditions is different, they present with a similar clinical appearance. This study compares the two diseases regarding the distribution of cells, which are expressing cell surface markers of interest for inflammatory responses. Monoclonal antibodies (MoAbs) were used in standard immunohistochemical procedures. CD1a+, CD80+ and CD86+ cells in the epithelium of OLP- and cGVHD lesions had the dendritic morphology of Langerhans cells (LC). Higher frequencies of CD1a+ LC as well as CD25+ cells were observed in the OLP epithelium than in the cGVHD epithelium. The OLP lesions showed higher frequencies of subepithelial cells expressing CD1a, CD86, CD4, CD8 and CD25 than the cGVHD lesions. Notably there was a significantly higher frequency of CD25+ cells in the epithelium and the connective tissue of OLP than in cGVHD. These cells might represent regulatory T cells. In conclusion, cGVHD and OLP show marked differences at the cellular level despite similar clinical appearance. Hence, the findings indicate differences in the regulation of the inflammatory response between the two conditions.
Adult↗
Intravenous lidocaine infusion in the treatment of experimental human skin burns - digital colour image analysis of erythema development.
Previous studies have shown that local anaesthetics possess a wide range of effects on the pathophysiology of burns, including inhibition of burn oedema and inhibition of progressive burn ischemia. The present randomised double-blind cross-over study in six volunteers investigated the effects of intravenous lidocaine infusion on partial thickness skin burns. A thermoprobe was used to induce a standardised thermal injury (1 cm(2)) on the flexor side of one forearm and was repeated on the opposite side 1 week later. Subjects received either an intravenous bolus dose of lidocaine (1 mg kg(-1)) immediately after the thermal trauma followed by continuous intravenous infusion of lidocaine (40 microg kg(-1) min(-1)) during 4 h or equal volumes of isotonic saline. Macrophotographs of the experimental skin area were taken preburn and 1, 2, 3, 4, and 12 h postburn and evaluated by computerised image colour analysis using normalised rgb (n-rgb) and Hue-Saturation-Intensity (HSI) colour systems as a quantitative measure of pathophysiological events. Maximum erythema occurred 2-3 h postburn. Differences between lidocaine- and placebo-treated burns were not significant during the first 4 h postburn. At 12 h postburn, the lidocaine-treated burn demonstrated a significantly faster restitution of residual erythema compared to control sites. The present study shows that intravenous lidocaine significantly inhibits the long-term inflammation-induced tissue responses to thermal trauma.
Adult↗
MedView-design and adoption of an interactive system for oral medicine.
MedView is a joint project with participants from oral medicine and computer science. The aim of the project is to build a large database from patient examinations and produce computerized tools to extend, view, and analyze the contents of the database. The contents of the data base is based on a formalization of health-care processes and clinical knowledge in oral medicine harmonized within the network SOMNET. We give an overview of the current status of the MedView project and discuss background and future directions.
Artificial Intelligence↗
Information visualisation in clinical medicine using 3D parallel diagrams: a case history.
An information visualisation tool was implemented and tested as a solution to the problem of visualising clinical experience derived from large amounts of formalised clinical data. The tool was based on the idea of dynamic 3D parallel diagrams with support for direct manipulation, an idea similar to the notion of 3D parallel coordinates. The tool was tested on a knowledge base containing about 1500 examinations obtained from different clinics. Clinical practice showed that the basic idea is conceptually appealing to the involved clinicians as the tool can be used for generating and testing of hypothesis.
Artificial Intelligence↗
Distribution of interleukin-2, -4, -10, tumour necrosis factor-alpha and transforming growth factor-beta mRNAs in oral lichen planus.
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.
Adult↗
Macrophages, dendritic cells and T lymphocytes in rat buccal mucosa and dental pulp following 5-fluorouracil treatment.
Cancer chemotherapeutic drugs may affect immunocompetent cells of oral soft tissues, causing an impaired capacity to induce immune defence reactions. This study was designed to investigate changes in the number of macrophages, dendritic cells and T lymphocytes in the oral mucosa and dental pulp following treatment with the antineoplastic agent 5-fluorouracil (5-FU). Rats were given 5-FU (30 mg/kg or 50 mg/kg) i.v. on days 0, 1, 2, 5, 6 and 7. The number of cells in buccal epithelium and dental pulp expressing ED2, MHC class II, or CD2 molecules was analyzed following immunohistochemical peroxidase staining. Major histocompatibility complex (MHC) class II molecules were analyzed in epithelial sheets and in epithelial cell suspensions by flow cytometry. Increasing concentrations of 5-FU changed the morphology of the epithelial Langerhans cells with a reduced dendritic appearance as the most prominent feature. At 50 mg/kg of 5-FU, the oral epithelium detached from the connective tissue at the basement membrane. MHC class II molecule-expressing cells were reduced in number in the lamina propria of the buccal mucosa and in the dental pulp after both low and high dose of 5-FU, but only after high dose in the epithelium. The number of ED2- and CD2-expressing cells in the dental pulp was only slightly reduced by 5-FU treatment at both low and high dose, while these cells decreased in number in the oral mucosa. The varying sensitivity to 5-FU by macrophages, dendritic cells, and T cells depending on the tissues in which they reside may be due to differences in cell origin or differences in antigenic load.
Animals↗
The significance of oral health and dental treatment for the postoperative outcome of heart valve surgery.
The objective of this study was to evaluate the significance of preoperative dental treatment for the development of complications in the form of infections during the first postoperative weeks after heart valve surgery. In one group of patients (n = 149), oral health was examined and dental treatment performed 3-6 months prior to heart valve surgery. In a second group (n = 104), oral health was examined postoperatively and these patients did not receive any dental treatment before surgery. Infections were recorded for all patients during the first three weeks after surgery and correlated to the dental status at the time of surgery. Sepsis or endocarditis occurred in 5.4% of the first group and in 1.9% of the second group. Freedom from all infections for the two groups was 55% and 56%, respectively. The results did not reveal any significant differences between the groups regarding patients' oral health at the primary oral examination. The frequencies of postoperative complications such as focal infections, fever and increased CRP were also found to be similar for both groups. The combined scores of complications were 2.1% and 1.8%, respectively. Data from the present study do not support the suggestion that dental intervention will decrease the rate of early complications following heart valve surgery.
Aged↗
Digital image analysis of erythema development after experimental thermal injury to human skin: effect of postburn topical local anesthetics (EMLA).
UNLABELLED: Local anesthetics inhibit edema and improve circulation in experimental burns. We evaluated the effect of topical local anesthetics on human skin burns in volunteers using computerized color analysis that allowed repeated noninvasive quantitative measurements. A standardized partial-thickness burn (1 cm2) was induced in one forearm of 10 healthy volunteers and in the opposite forearm a week later. The burned areas were treated with lidocaine/prilocaine cream (EMLA; Astra, Sweden) or a placebo cream for 1 h. The experimental skin area was photographed before and 1, 2, 4, and 12 h postburn. Digitized images were evaluated using normalized red-green-blue and Hue-Saturation-Intensity. Differences in erythema between skin treated with EMLA and placebo were not significant during the first 4 h postburn. However, 12 h postburn, a pronounced decrease in the degree of erythema was observed in EMLA-treated skin compared with placebo-treated skin. We conclude that topical local anesthetics administered for 1 h postburn significantly reduces the duration of erythema after a mild thermal injury, which suggests a potential use in clinical practice in the treatment of minor skin burns. IMPLICATIONS: Burn injury constitutes a serious type of tissue damage that activates inflammatory mechanisms, often causing pain, disfiguration, or malfunction. We treated burns using an anesthetic cream and demonstrated a reduction in burn-induced inflammation by using computer-based color image analysis.
Administration, Topical↗
Langerhans cells from oral epithelium are more effective in stimulating allogeneic t-cells in vitro than Langerhans cells from skin epithelium.
Dendritic cells, such as Langerhans cells (LC), in different ectodermal compartments may have different functional capabilities. The present study was undertaken to compare oral Langerhans cells (LC) with those of the epidermis in terms of their ability to co-stimulate T-cells in vitro. A Mixed Epithelial Cell Lymphocyte Reaction (MELR) and a mitogen-driven (concanavalin A) T-cell proliferation assay were used. In both assays, LC in a crude cell suspension of freshly isolated oral epithelial cells were found to be five times more effective in mediating T-cell proliferation than freshly isolated epidermal LC. Twenty-four-hour cell culture at 37 degrees C enhanced the T-cell response in the MELR compared with cells cultured at 4 degrees C. This applied to both skin and oral epithelial cells. Oral and skin epithelial cell suspensions depleted of LC lost the capacity to stimulate allogeneic T-cells. Incubation of the epithelial cell suspensions with recombinant Granulocyte/Macrophage-Colony Stimulating Factor (rGM-CSF) did not enhance the co-stimulating capacity of the LC. Titration of different numbers of oral and skin LC to T-cells showed that skin LC were never able to reach more than 44% of the maximal stimulatory capacity of oral LC. Data show that oral LC are more efficient than skin LC in providing co-stimulatory signals to T-cells, suggesting a difference in functional capacity between the two cell populations.
Animals↗
Reduced in vivo cell-mediated immune responses to mumps, tuberculin, and streptokinase/streptodornase but not to Candida albicans in oral lichen planus.
Oral lichen planus is considered to be a T-cell-mediated disease. The purpose of this study was to investigate the capacity of T-lymphocytes in oral lichen planus patients to respond to a number of commonly encountered environmental antigens in vivo. To do this, we assessed dermal delayed-type hypersensitivity responses to mumps, streptokinase/streptodornase, Candida albicans, and purified protein derivative of tuberculin (PPD) in 17 oral lichen planus patients and in matched controls. Reduced induration in response toward mumps, PPD, and streptokinase/streptodornase was demonstrated in oral lichen planus patients compared with controls. In addition, the total sum of induration diameters was decreased in the patients. However, C. albicans stimulation resulted in similar levels of response in both groups. The differences in induration size between matched patients and controls for mumps and PPD were thus significantly greater than the corresponding differences for the C. albicans antigen. This suggests that a selective difference in the response to these antigens exists in oral lichen planus patients. The results may point to a loss of memory T-helper function to infrequently encountered environmental antigens, represented by mumps, PPD, and streptokinase/streptodornase, contrarily to memory function to common antigens (C. albicans), which seem to be unaffected.
Aged↗
Effects of root canal sealers on immunocompetent cells in vitro and in vivo.
Over the years of testing biocompatibility of endodontic filling materials, little attention has been paid to the potential adverse influences on the function of the immune system. Therefore, the purpose of this study was to investigate the extent to which extractable components of some commonly used root canal sealing materials (ERCS) may interfere with immunocompetent cells in vitro. The potential of these materials to cause delayed-type hypersensitivity (DTH) was also addressed in a rat model system. Extractable components were drawn in cell culture medium from freshly mixed or set material of AH 26. Grossman's sealer, Endomethasone, and Apexit. In-vitro assays included either spleen cells or rat pulp tissue cells that were released following enzymatic digestion with collagenase. Purified T cells for the pulpal cell assay were obtained from rat mesenteric lymph nodes. The effect of ERCS on the proliferation of concanavalin A (con A) stimulated spleen cell was measured by 3H-thymidine incorporation. Pulpal accessory cell function was monitored by the capacity of pulpal cells, pretreated with components of ERCS, to provide signals to con A stimulated T cells. DTH was tested after subcutaneous implantation of root canal sealers (RCS) in rats and challenge by ear injection. Pretreatment of pulpal cells with low dilutions of eluates from extracted AH 26 and Endomethasone resulted in a strong reduction of the T cell proliferation rate. The effect was considerably reduced (P < 0.01) when extracts of the solid material were employed. Extracts of Grossmans' sealer and Apexit affected T cell proliferation only to a limited extent in the pulpal cell assay. In general, assays on spleen cells showed a similar profile, although increased cell division was induced by Grossman's sealer at high eluate dilutions and a concentration-dependent decrease of cell division at lower concentrations of this material. ERCS evoked both immunosuppression and, in some instances, immunostimulation, but they did not release DTH.
Administration, Topical↗