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P B Sugerman

Publications and source records attributed to P B Sugerman.

32 records · Page 2Linked to original sources

A quantitative cytological study of lesional and non-lesional mucosa in oral lichen planus.

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.

Adult↗

TCR V beta gene expression in lesional T lymphocyte cell lines in oral lichen planus.

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.

Adult↗

Exfoliative cytology in clinical oral pathology.

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.

Cytodiagnosis↗

Heat shock protein expression in oral epithelial dysplasia and squamous cell carcinoma.

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)

Biomarkers, Tumor↗

Heat shock protein expression in oral lichen planus.

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.

Adult↗

Review article: The role of oncogenes, tumour suppressor genes and growth factors in oral squamous cell carcinoma: a case of apoptosis versus proliferation.

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.

Animals↗

Phenotype and suppressor activity of T-lymphocyte clones extracted from lesions of oral lichen planus.

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.

Adult↗

Disease mechanisms in oral lichen planus. A possible role for autoimmunity.

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.

Autoimmune Diseases↗

Clonal expansion of lymphocytes from oral lichen planus lesions.

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.

Adult↗

Phenotypic and functional analysis of peripheral blood lymphocytes in oral lichen planus.

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.

Adult↗

Suppressor cell function in 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.

Adult↗

Oral lichen planus.

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Adult↗