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Biomedical subjects

P R Morgan

Publications and source records attributed to P R Morgan.

At least 19 recordsLinked to original sources
PubMed2006

DNA ploidy in proliferative verrucous leukoplakia.

Proliferative verrucous leukoplakia (PVL) is a clinicopathologically distinctive form of oral leukoplakia presenting with multifocal flat, nodular and verrucous lesions that progress inexorably to squamous carcinoma. The aims of this investigation were to describe the clinical and histopathological features of six cases of PVL and to determine whether lesional epithelium demonstrates DNA ploidy anomalies prior to malignant transformation. The clinical and pathological features of six patients were reviewed and all biopsy specimens were subjected to image-based DNA ploidy analysis. The female:male ratio was 5:1 and the average age on first biopsy was 66 years. Only one patient reported both tobacco smoking and alcohol intake. The most frequently affected sites were alveolar ridge and/or gingiva (6/6), buccal mucosa (3/6), palate (3/6), tongue (2/6), buccal sulcus (2/6), and lip (1/6). Three patients developed multiple primary carcinomas, either invasive or verrucous. A ploidy anomaly at any oral site would have predicted malignant transformation in four cases and probably in a fifth for whom DNA ploidy failed to meet diagnostic criteria but was suspicious of aneuploidy. The site of transformation was predicted by ploidy and histopathology for three carcinomas and a further carcinoma showed severe dysplasia and a suspicious ploidy result in adjacent tissue. Both conventional histopathology and DNA ploidy proved effective in predicting the site of transformation in this limited series.

Aged↗
PubMed2005

Association of CXCL13 and CCL21 expression with the progressive organization of lymphoid-like structures in Sjögren's syndrome.

OBJECTIVE: Ectopic lymphoneogenesis can occur in the salivary glands of Sjögren's syndrome (SS) patients and is associated with local antigen-driven B cell responses, autoantibody formation, and potential lymphomatous transformation. CXCL13 and CCL21 have been identified in salivary glands, but their role in ectopic lymphoneogenesis in SS remains unclear. This study aimed to evaluate the microanatomic association between CXCL13 and CCL21 expression and the acquisition of lymphoid features in periductal foci. METHODS: Salivary glands from 37 SS patients and 9 chronic sialadenitis patients were analyzed by immunohistochemistry for T cell/B cell segregation, CD21+ follicular dendritic cell networks, and peripheral lymph node addressin (PNAd)-positive high endothelial venules (HEVs) in relationship to the size of the aggregates and the expression of CXCL13 and CCL21 within infiltrating cells, epithelium, and endothelium. RESULTS: Grade 1 aggregates (10-50 lymphocytes) demonstrated predominance of nonorganized CD3+ cells, while grade 2 (>50 lymphocytes) and grade 3 (>50 with germinal centers) showed a progressive increase in CD20+ B cells and T cell/B cell segregation. This higher degree of lymphoid organization was significantly related to an increased expression of CXCL13 within infiltrating cells and PNAd+ HEV-associated CCL21-producing cells. Conversely, no association between lymphoid organization and lymphoid chemokine expression by epithelial cells was observed. CONCLUSION: The acquisition of lymphoid features by inflammatory foci in SS is critically associated with the enlargement of the inflammatory foci and with the expression of CXCL13 and CCL21 within the infiltrate, but is not associated with their expression by epithelial cells. These data strongly support an active participation of CXCL13 and CCL21 in regulating the progressive organization and maintenance of periductal foci.

Adult↗
PubMed2004

Congenital sialolipoma of the parotid gland first reported case and review of the literature.

Tumours of the parotid gland in children are uncommon, and represent only 1.3% of all benign salivary tumours. Lipomas of the parotid are also rare, and account for 0.5% of all parotid gland tumours. Sialolipoma is a new variant of salivary gland lipoma, consisting of adipose and glandular tissue that was first proposed by Nagao et al. in 2001. Ten cases of parotid gland lipoma associated with glandular elements have been previously reported in the literature. All have been in adults and none in children. We present the first reported case of congenital sialolipoma that had developed in a female infant. It was managed successfully by superficial parotidectomy undertaken at ten weeks of age.

Female↗
PubMed2001

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.

Carcinoma, Squamous Cell↗
PubMed2001

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.

Carcinoma, Squamous Cell↗
PubMed2000

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.

Cell Differentiation↗
PubMed2000

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.

Adult↗
PubMed2000

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.

Antibodies, Monoclonal↗
PubMed1999

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.

Antigens, Nuclear↗
PubMed1999

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.

Adenoma, Pleomorphic↗
PubMed1998

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.

3T3 Cells↗
PubMed1998

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.

Adult↗