Biomedical subjects
P R Morgan
Publications and source records attributed to P R Morgan.
Cutaneous endometriosis and its association with caesarean section and gynaecological procedures.
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Recurrence of cutaneous malignant melanoma at 24 years, mimicking ovarian malignancy.
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Expression of keratins in normal, immortalized and malignant oral epithelia in organotypic culture.
Keratins have been extensively studied in tissues and cultured keratinocytes but limited information is available on epithelia reconstructed in vitro. The aim of this study was to examine keratin expression in organotypic epithelia with normal (NOK), immortalized (SVpgC2a) and malignant (SqCC/Y1) human buccal cells. Organotypic epithelia were derived from 10 days of culture at the air-liquid interface of collagen gels containing human oral fibroblasts using a standardized serum-free medium. Sections were stained immunohistochemically with selected mono-specific antibodies to a range of keratins. Organotypic epithelia showed sharp differences in keratin expression and distribution. K4/K13, K1/K10, K6/K16 were variably expressed in NOK and SqCC/Y1 but were not detected in SVpgC2a. K5 was expressed in all organotypic epithelia but K14 was absent in SVpgC2a. K7 and K8 showed variable expression while K18 was expressed uniformly in all epithelia. K19 was expressed consistently in NOK and K20 was distributed heterogeneously in SVpgC2a. Overall, organotypic cultures of normal keratinocytes express many of the same keratins as buccal mucosa. Further, the loss of keratins in SVpgC2a and their retention in SqCC/Y1 have several features in common with the respective keratin profile of oral epithelial dysplasia and well-differentiated oral squamous cell carcinoma. Although qualitative and quantitative differences exist compared to keratin expression in vivo, these cell lines in organotypic culture may serve in studies of the multi-step progression of oral cancer.
Gene expression of differentiation-specific keratins in oral epithelial dysplasia and squamous cell carcinoma.
The aim of the study was to investigate the differentiation-specific keratins (K4, K13, K1 and K10) in oral epithelial dysplasia and squamous cell carcinoma (SCC). Alterations in keratin gene expression were determined by in situ hybridization using 35S-labeled riboprobes and immunohistochemistry with monoclonal antibodies. In mild dysplasia, both sets of differentiation keratins were expressed in the same group of cells but in moderate lesions, expression of K4 and K13 was reduced in the presence of enhanced K1 and K10 synthesis. In severe dysplasia, neither mRNAs nor proteins were detected. In tumor islands of well and moderately differentiated SCCs, the K4/K13 complex was co-expressed with K1/K10, but in poorly differentiated carcinomas, differentiation keratins were absent. Consequently, mild oral epithelial dysplasia and well differentiated SCC retain an essentially normal pattern of keratin gene expression and hence epithelial differentiation while in severe dysplasia and poorly differentiated SCC keratin gene expression reflects the gross changes in epithelial differentiation and maturation.
Gene expression of differentiation-specific keratins (K4, K13, K1 and K10) in oral non-dysplastic keratoses and lichen planus.
Gene expression for the differentiation-specific keratins (K4, K13, K1 and K10) was analyzed in oral non-dysplastic keratoses, oral lichen planus (OLP) and lichenoid reactions (LR) by comparative in situ hybridization (ISH) and immunohistochemistry (IHC) to investigate molecular changes in the altered differentiation pattern from non- to para- or orthokeratinization. At the protein level, K4 and K13 were detected homogeneously in the suprabasal compartment of parakeratotic epithelium but showed reduced expression in orthokeratoses, particularly in the presence of lymphocytes. Corresponding transcripts were restricted to basal and lower prickle cells. Synthesis of K1 and K10 was upregulated and more pronounced in orthokeratotic epithelia. The study showed an alteration in the pattern of differentiation-specific keratins, although involvement of the lymphocytic infiltrate in OLP and LR resulted in further gene modulation. In both diseases, K1 and K10 showed transcriptional control, proteins having the same distribution as their transcripts. This represented a change from post-transcriptional regulation in normal buccal epithelium, in which mRNAs for K1 and K10 are more widely expressed than their proteins. Thus, the pattern of keratin gene expression may be altered in response to frictional/smoking stimuli or immune-mediated mechanisms.
Cowden's syndrome (multiple hamartoma and neoplasia syndrome): diagnostic dilemmas in three cases.
Cowden's syndrome is a multisystem disease inherited as an autosomal dominant trait with incomplete penetrance and variable expression. The disease has typical oral manifestations which often precede more systemic involvement, and the dental professional is therefore well placed to institute a regime of regular checks to ensure early treatment of any neoplasms which may occur. However, since not all of the classical signs are present in all patients, diagnosis may be difficult. The case report of a patient with most of the features of Cowden's syndrome is presented and features compared with two other possible cases.
muc-1 gene expression in head and neck squamous cell carcinomas.
Polymorphic epithelial mucin (PEM), the protein product of the gene muc-1, is a surface glycoprotein that is produced by a range of normal epithelial cells, but has been shown to be expressed at high levels in a range of adenocarcinomas. It has not been investigated extensively in head and neck related tissues, and not at all in head and neck squamous cell carcinomas (HNSCC). This immunohistochemical investigation using two monoclonal antibodies to muc-1 represents a baseline study of 18 HNSCC. In 13 cases, the glycoprotein was expressed at varying levels, usually in keratinizing foci. Although less prominent, expression was also present to some degree in nine of 23 control specimens of non-neoplastic mucosa, mostly at an epithelial level early in the parakeratinization process. Both antibodies showed a pattern of staining. The cellular basis for muc-1 expression is speculative at present and although it is at a lower level than in adenocarcinomas, it may help to provide further insight into epithelial cell differentiation in squamous cell carcinomas.
Quantitative assessment of apoptosis in oral lichen planus.
OBJECTIVE: The aims of this study were to examine the frequency of apoptoses in oral lichen planus by in situ end labeling, to ascertain whether this technique is as sensitive as conventional histologic analysis, and to examine the effect of lymphocytic infiltration. STUDY DESIGN: Numbers of apoptoses in hematoxylin-eosin stained sections were compared with numbers of apoptotic nuclei identified by in situ end labeling in oral lichen planus (n = 26) and normal buccal epithelium (n = 8). Immunohistochemical staining with MIB-1 and for Bcl-2 and Bax enabled possible regulatory pathways to be investigated. RESULTS: In oral lichen planus, approximately 1 apoptotic cell was detected per millimeter of basal layer, cell death increasing with lymphocytic infiltration. Epithelial cell proliferation did not correlate with apoptosis. Bcl-2 expression was weak or absent in basal cells, and Bax was localized to upper prickle cells. CONCLUSIONS: Increased numbers of apoptoses were detected in oral lichen planus, especially in association with lymphocytic infiltration, higher numbers being seen with hematoxylin-eosin staining than with in situ end labeling.
A case of metastasizing pleomorphic adenoma.
The pleomorphic adenoma is the most common benign salivary neoplasm. A case is presented in which a palatal pleomorphic adenoma seeded a metastasis in the medullary cavity of the anterior maxilla, apparently by hematogenous spread after surgical manipulation.
Papulonecrotic tuberculide complicating scrofuloderma in a health-care worker.
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A measure of the mitotic index: studies of the abundance and half-life of p34cdc2 in cultured cells and normal and neoplastic tissues.
BACKGROUND: The cdc2 gene encodes a protein kinase, p34cdc2, that is essential for mitosis, and is present at high levels in dividing cells. Classical studies of the levels of this protein in dividing and resting cells used antibodies that cross-react with other members of the CDK family, in particular with CDK2. We have therefore re-examined the abundance of p34cdc2 in a variety of tissues and cell lines, using a highly specific, epitope-mapped monoclonal antibody that does not react with CDK2. RESULTS: We observed high levels of p34cdc2 in proliferating cells, especially those in neoplastic tissues. Cells that have withdrawn from the cell cycle have low or undetectable levels. At the end of mitosis, the level of p34cdc2 declines, with simple first-order kinetics, with a half-life which is never less than 6h and is more typically about 18h. The persistence of p34cdc2 after the last cell division is comparable to that of PCNA, a commonly used marker of proliferation. CONCLUSIONS: The immunochemical detection of p34cdc2 provides an accurate, reliable and meaningful measure of the proliferative activity of cells in tissues. We suggest that p34cdc2 should be considered as the most authentic molecular marker of the mitotic index.
Oral self-mutilation masquerading as malignancy.
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Gene expression of differentiation-specific keratins (4/13 and 1/10) in normal human buccal mucosa.
The aim of the present study was to compare gene expression of the major differentiation-specific keratins in oral epithelium: keratins 4, 13, 1, and 10. Previous studies have shown that the dominant keratins in normal buccal epithelium are K4 and K13, with minor populations of cells showing K1 and K10 expression; herein, we have further examined expression of these keratins at the mRNA level. Six biopsies from normal buccal mucosa were immunohistochemically stained for keratin proteins by means of monoclonal antibodies to K4, K13, K1, and K10. Adjacent sections were processed for mRNA by nonisotopic in situ hybridization, using specific riboprobes labeled with digoxigenin. Proteins for K4 and K13 were expressed suprabasally throughout buccal epithelium, with columns of cells staining additionally for K1 and K10. In situ hybridization revealed a comparable pattern of mRNA distribution for K4 and K13, with expression restricted to parabasal and lower prickle cells. Transcripts for K1 and K10 were present in basal, parabasal, and lower prickle layers, showing a much wider expression than that of their proteins. This study has shown that in buccal epithelium, there is extensive mRNA expression of the "inappropriate" differentiation-specific keratins, despite minimal protein expression. This suggests that K1 and K10 are regulated at the post-transcriptional level, so that they may be expressed adaptively as proteins. The findings will form a useful baseline for the study of these keratins in pathologically altered oral epithelia as well as in nonkeratinized epithelia from extra-oral sites.
Cell cycle regulatory proteins--an overview with relevance to oral cancer.
The cell cycle is controlled by a number of highly conserved proteins, found in species as diverse as yeast and mammals. The study of these proteins is a rapidly advancing field that is increasing our understanding of normal and abnormal cell division. Disruption of the cell cycle has been demonstrated in several different types of neoplasm, and there is increasing evidence that, in head and neck tumours, there is aberrant control of cyclins, cell cycle protein kinases and their inhibitors. Because of the phase specificity of some of the control proteins, antibodies to them are proving to be of value in studying cell kinetics of both normal tissues and malignant tumours.
Kindler syndrome: a rare cause of desquamative lesions of the gingiva.
Kindler syndrome is a rare syndrome with cutaneous and intraoral manifestations. It has been suggested that there is an overlap between this syndrome and another called Weary syndrome. Only 68 cases of Weary and Kindler syndromes have been reported, with fewer solely attributed to Kindler syndrome. The salient cutaneous features are neonatal bullae, poikiloderma, photosensitivity, and acral atrophy. This article presents the clinical intraoral findings of two siblings of consanguineous descent diagnosed as having Kindler syndrome. Both had an erythematous and erosive appearance of the gingiva; one sibling had poor oral hygiene and a rapidly progressive form of periodontal disease; the other, whose oral hygiene was acceptable, had no detectable bone loss.
Hybrid central giant cell granuloma and central odontogenic fibroma-like lesions of the jaws.
Ten lesions from eight cases are presented of a rare intra-osseous jaw lesion with the combined histological features of giant cell granuloma and central odontogenic fibroma. Lesions arose over a wide age range and presented as monolocular or multilocular radiolucencies with cortical expansion and, in one case, perforation. Two lesions recurred after curettage, one being eradicated by a second curettage and one by conservative excision. Histologically, zones of typical giant cell granuloma lay in a fibrous stroma containing islands, strands and clusters of epithelial cells. Islands often contained duct-like spaces or hyaline basement membrane globules. Trabeculae of osteoid were present in five lesions. Recurrent lesions showed features identical to the initial lesion, including recurrence of the prominent epithelial component. These features cannot be conclusively ascribed to a variant of either giant cell granuloma, central odontogenic fibroma or aneurysmal bone cyst, but the clinical features are slightly more suggestive of giant cell granuloma. Attention is drawn to the characteristic and potentially confusing histological appearances. The presence of giant cell granuloma-like areas in central odontogenic fibroma-like lesions is associated with an increased risk of recurrence following curettage.
Chronic sialadenitis in patients with nodal osteoarthritis.
Amongst the patients attending our combined oral medicine/rheumatology clinic, we have identified a subset presenting with xerostomia due to non-specific sialadenitis, who also suffer from generalized nodal osteoarthritis (NOA). We have called this combination SOX syndrome: sialadenitis, osteoarthritis and xerostomia. In this study, we have examined the characteristics of these patients clinically and histologically, and then determined the prevalence of SOX syndrome in patients with NOA compared to healthy age-matched controls. Patients were obtained from rheumatology clinics and a local old people's home. The series consisted of 35 patients with NOA and 18 age- and sex-matched controls without evidence of NOA or inflammatory rheumatic disease. There was no significant difference in age and sex between the two groups. None were on drugs known to induce xerostomia. The subjects were assessed for whole salivary, parotid saliva and lacrimal flow, autoantibodies, rheumatoid factor (RF) and erythrocyte sedimentation rate (ESR). The whole saliva flow (mean +/- 95% CI) was 0.32 +/- 0.07 ml/min for the NOA group and 0.54 +/- 0.17 ml/min for the control group. The difference is statistically significant (P < 0.05, two-tailed Student's t-test). No statistically significant difference was found in the parotid and lacrimal flow rates of NOA and controls. Nine of the 35 NOA patients had reduced whole salivary flow (normal range > 0.02 ml/min) compared with only one out of 18 in the control group (P > 0.05, chi 2 test). All NOA patients with xerostomia and reduced whole salivary flow were RF, anti-Ro and anti-La negative, and had a normal ESR. Thus, 25% of subjects with NOA had clinical and laboratory features of SOX syndrome, suggesting that this is a defined disease entity.