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Biomedical subjects

P R Morgan

Publications and source records attributed to P R Morgan.

At least 37 records · Page 2Linked to original sources

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.

Animals↗

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.

Adult↗

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.

Adolescent↗

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.

Adult↗

Cytokeratin phenotypes at the dento-gingival junction in relative health and inflammation, in smokers and nonsmokers.

OBJECTIVES: The cells of the junctional epithelium (JE) provide and maintain the epithelial attachment, and remain morphologically and phenotypically distinct from oral sulcular (OSE) and external oral epithelia (EOE), from which they may be regenerated de novo. Expression of cytokeratins (CK) in human epithelia has been shown to be highly site-specific, implying a functional role. The aims of this study were to differentiate between the cytokeratin profiles of JE, OSE, EOE and pocket epithelia (PE) in health and disease, in smokers and non-smokers. MATERIALS AND METHODS: The cytokeratin profiles of 40 samples of healthy and clinically inflamed human gingival tissue taken from 15 smokers and 25 non-smokers were studied by immunocytochemistry. Cryostat sections of fresh frozen gingival tissues were stained with a panel of monoclonal antibodies (mAb) and visualised by a biotin-Streptavidin-peroxidase complex technique. RESULTS: JE and PE expressed an identical range of cytokeratins irrespective of the inflammatory or smoking status, with the exception of CK4 expression, which tended to be increased in smokers. The OSE and EOE expressed non-cornifying and cornifying differentiation cytokeratins respectively, but in the presence of inflammation, both these epithelia showed increased expression of CK19 at a basal level in association with expression of one or more of the simple cytokeratins. JE/PE expressed CK17 in external layers only, approximating the tooth surface. All epithelia expressed CK6, 16 the markers of high cell turnover. CONCLUSIONS: CK 19 was a consistent differentiation marker for JE and PE. Expression of CK8, 18 was enhanced by inflammation. CK4 expression increased in association with smoking. Markers of differentiation were not always co-expressed equally within a pair. Pairs were not always completely mutually exclusive with frequent co-localisation.

Adolescent↗

The localization of p34cdc2 in the cells of normal, hyperplastic, and malignant epithelial and lymphoid tissues of the oral cavity.

The expression of p34cdc2 has been examined in normal, hyperplastic, and malignant oral epithelia and lymphoid tissues. Four monoclonal antibodies were prepared against Xenopus p34cdc2, three of which react specifically with human p34cdc2 and not with p33cdk2. These produced similar patterns of staining in both fixed and frozen sections of human material. Staining occurred mainly in the proliferative compartments of normal and hyperplastic tissues. In normal oral epithelia, parabasal and basal cells were the most strongly stained, with lighter cytoplasmic staining in lower prickle cells. In tonsillar germinal centres, a high proportion of cells was stained, with fewer positive cells in interfollicular zones, a distribution in keeping with the known pattern of cell proliferation. In normal cells, the intracellular location of p34cdc2 was cytoplasmic until early prophase, but in oral squamous cell carcinomas and lymphomas, it was located in both cytoplasm and nucleus during interphase and a larger fraction of cells was positive than in the equivalent normal tissues. Higher-grade neoplasms showed both a higher intensity of staining and a higher proportion of p34cdc2-positive cells.

Antibodies, Monoclonal↗

Expression of cytokeratin messenger RNA versus protein in the normal mammary gland and in breast cancer.

It is not known how tightly regulation of cytokeratin (CK) protein expression is correlated with transcriptional activity in breast cancer. The level of control of CK expression in the normal mammary gland and in breast cancer has been assessed by combining in situ hybridization with riboprobes, and with immunohistochemistry using monospecific antibodies. In normal mammary gland, luminal cells showed abundant hybridization with complementary RNA (cRNA) probes for CK7, CK8, CK18, and CK19. Proteins of these CKs were correspondingly distributed except for that of CK19, which showed a heterogeneous staining. In primary carcinomas, both messenger RNAs (mRNAs) and proteins of CK8 and CK18 were generally expressed to a degree similar to that of normal epithelia, but a lower level of mRNA and protein of CK18 was observed in metastatic carcinomas. Reduced expression of CK7 and CK14 was observed in all carcinomas, and the correlation between mRNA and protein for these two cytokeratins was unbalanced, whereas the expression of CK19 mRNA and the proportion of its protein-positive cells were increased. The results suggest that these major CKs in normal mammary gland epithelia are regulated at the transcriptional level except for CK19, which is partially under the posttranscriptional control. The alterations observed in breast cancer are not only reflected by the reduced or increased expression of individual cytokeratins, but characterized by partial loss of the normal regulation of cytokeratin expression.

Adult↗

Keratin 14 and 19 expression in normal, dysplastic and malignant oral epithelia. A study using in situ hybridization and immunohistochemistry.

Specific mRNA and protein for two major keratins, K14 and K19, were investigated in normal, dysplastic and malignant oral epithelia by combined in situ hybridization and immunohistochemistry. In normal epithelia, K14 mRNA and protein were present almost exclusively in the basal layer of non-cornified, and in rete-processes of cornified, sites. Dysplastic epithelium showed irregular extension of the K14 transcript and protein into superficial cells. In squamous cell carcinoma (SCC), K14 transcript was abundant in most samples whilst in one poorly differentiated carcinoma mRNA but no protein was detected. K19 mRNA and its protein were present predominantly in basal cells of noncornified epithelium, whereas in cornified epithelium only mRNA was detected. In dysplasias, K19 transcript was detected in all specimens but its protein was absent in most cases. Even more variations of K19 expression were observed in SSC. These findings indicate differences in the control of expression of K14 and K19 in normal epithelia and show that regulation is further disturbed during dysplastic change and malignancy.

Autoradiography↗

p53 immunohistochemistry of odontogenic keratocysts in relation to recurrence, basal-cell budding and basal-cell naevus syndrome.

Mutation of the p53 tumour suppressor gene can produce a more stable protein that does not inhibit mitosis, accumulates in the nucleus and can then be detected immunohistochemically in many human tumours using antibody CM-1. The protein has also been detected in odontogenic keratocysts. Routinely processed material from 30 odontogenic keratocysts was immunostained with antibody CM-1. Ten were recurrences and five were associated with the basal-cell naevus syndrome (Gorlin-Goltz syndrome). p53 protein was found in 50% (15/30) of the odontogenic keratocysts, in 53.3% (8/15) of non-recurrent cysts, in 40% (4/10) of recurrent cysts and in 60% (3/5) of those associated with the basal-cell naevus syndrome. Staining was weak and speckled and limited to occasional basal and suprabasal cells. There was no statistically significant difference in staining between these groups and no correlation between expression and the presence of satellite cysts, basal-cell budding or islands of odontogenic epithelium. The low levels of expression may represent physiological expression of wild-type p53 protein rather than mutant or complexed p53 protein.

Antibodies↗

An unusual intraosseous melanoma in the maxillary alveolus.

A case is reported of a 31-year-old white man who presented with a solitary melanoma in the maxillary alveolus. The lesion was located between and had displaced the roots of the lateral incisor and canine and was relatively well circumscribed on radiography. No mucosal origin or potential primary lesion was found, and a marginal excision resulted in the patient remaining free from disease after 7 years of follow-up. Metastasis of melanoma to the jaws is rare even in disseminated disease, and this solitary lesion is unusual. Although metastasis from a regressed primary tumor cannot be excluded, some of the features raise the possibility that this melanoma may have arisen as a primary tumor within bone.

Adult↗

Immunohistochemical characterisation of odontogenic cysts with mesenchymal and myofilament markers.

The aim of the present investigation was to analyse the fibroblast phenotype in the main groups of odontogenic cysts. We have examined the muscle differentiation markers alpha-smooth muscle actin (ASMA) and desmin and the presence of vimentin using immunocytochemistry. Fibroblasts of other cyst types, hyperplastic fibrous lesions, and from several normal sites were used as controls. All fibroblasts stained for vimentin, but a variable proportion of cyst wall fibroblasts were also positive for the antibody to ASMA. Their distribution was not random and two positive zones could be distinguished, an inner subepithelial layer and an outer region adjacent to the bone-facing surface. This staining pattern was observed for all the types of odontogenic cysts studied, although the subepithelial staining was more frequent in the presence of an inflammatory infiltrate. The contractile nature of these cells was supported by their ultrastructural appearance. Some non-odontogenic cysts showed subepithelial fibroblasts strongly labelled with ASMA; in the control tissues ASMA was negative except for pericytes and some groups of cells in supracrestal gingiva. These results demonstrate a distinct cell population with a myofibroblast phenotype in the odontogenic cyst wall and with a distribution which may enable them to contribute to wall elasticity constraining cyst expansion. Their presence in all types of odontogenic cyst studied would suggest that myofibroblast formation is independent of the pattern of cyst growth.

Actin Cytoskeleton↗

The prognostic value of individual histologic grading parameters in small lingual squamous cell carcinomas. The importance of the pattern of invasion.

BACKGROUND: The histologic grading of the deep invasive margin of oral squamous cell carcinoma recently has been shown to have prognostic value, but previous series have not been homogeneous enough to allow grading parameters to be assessed individually. METHODS: Forty-seven small lingual carcinomas limited to the lateral border of the tongue and treated by radiotherapy were graded histologically at their deep invasive front. Clinical and grading parameters were correlated by statistical tests performed by permutational techniques. RESULTS: Carcinoma recurred locally in 6 patients, and metastases developed in 19. Local recurrence correlated with Broders' grade (P = 0.0143), keratinization (P = 0.017) and pattern of invasion (P = 0.0195). Metastasis had a highly significant correlation with Broders' grade (P < 0.001), pattern of invasion (P < 0.001), and invasive front grading total score (P < 0.001). Seven of 8 carcinomas with diffuse infiltrating patterns metastasised, whereas only 4 of 25 with large islands or a broad infiltrating pattern metastasized. CONCLUSIONS: The usefulness of the deep invasive front grading system for small lingual carcinoma was demonstrated. The pattern of invasion was the component of the grading system that had the closest correlation with metastasis and recurrence in this type of carcinoma.

Carcinoma, Squamous Cell↗

Determining the dental origins of foreign bodies in foodstuffs: applications of a new microscopic technique.

The use of confocal optical microscopes is reported as a method for histologically identifying foreign bodies, alleged to be of dental origin, found in foodstuffs. This technique offers the advantages of allowing rapid evaluation of a sample, without causing its destruction due to the production of thin sections which are normally required for conventional histology. The system has been used to identify fragments of dental origin, allegedly found by customers in foodstuffs which are marketed by a major retail chain.

Animals↗

Intermediate filaments in oral neoplasia. I. Oral cancer and epithelial dysplasia.

The major value of intermediate filaments (IFs) in biological and applied research lies in their high order of cell and tissue specificity. This is particularly well illustrated in keratin (K) expression in various oral epithelia. Although the original class of IF is usually conserved in tissues after neoplastic transformation, epithelia show a tendency to shift their pattern of keratin expression in a manner which, while not predictable with precision, may sometimes be of diagnostic or prognostic significance. This review compares the keratins in normal oral epithelia, which show a mainly site-dependent expression, with those in squamous cell carcinoma. Key changes in the latter are the presence of simple epithelial keratins, K8 and K18 (occasional K7), reduced expression of differentiation-linked keratins (K1, K10, K4 and K13) and a tendency for down-regulation of primary keratins, K5 and K14. Moderate and severe dysplasias also tend to exhibit K8 and K18 with concomitant disordered expression of differentiation-linked keratins. There are reports of similar changes after neoplastic transformation in other mucosal sites and skin. Before this information can be applied diagnostically in immunocytochemical studies, the anti-keratin antibodies must be fully characterised and their interaction with the relevant tissue, both frozen and conventionally processed, should be evaluated.

Carcinoma, Squamous Cell↗

Protein and mRNA expression of simple epithelial keratins in normal, dysplastic, and malignant oral epithelia.

Simple epithelial keratins K7, K8, and K18 are present in no more than trace amounts in normal stratified squamous epithelial but have been reported in squamous cell carcinomas. With the aim of determining the level at which keratin synthesis is regulated in vivo, we have compared the expression of mRNA by in situ hybridization and protein by immunohistochemistry for K7, K8, and K18 in a series of normal, dysplastic, and malignant oral epithelia. In normal epithelia mRNAs for K7, K8, and K18 were present in basal and lower spinous cells but adjacent sections were generally negative for the respective proteins. In severe dysplasia there was irregular suprabasal extension of K8 and K18 mRNAs in all cases and their proteins were expressed in more than half of the cases. The carcinomas expressed K8 and K18 mRNAs homogeneously and were strongly reactive for these keratin proteins but K7 expression appeared reduced in malignancy. These results are consistent with the post-transcriptional regulation of K7, K8, and K18 expression in normal epithelia and the presence of their proteins in dysplastic and malignant epithelia suggests the release of these epithelial cells from a post-transcriptional block on K8 and K18 translation. Alternatively, rapid degradation of K8 and K18 protein might be occurring in normal epithelia but be suppressed in dysplasia and malignancy.

Base Sequence↗

Erythema migrans: an unusual presentation.

A case of erythema migrans affecting the attached gingivae and the upper and lower labial mucosa is described. No lesions were found on the tongue although this is the site most commonly affected.

Adult↗

Epstein-Barr virus-related oral T-cell lymphoma associated with human immunodeficiency virus immunosuppression.

Epstein-Barr virus (EBV) is generally held to infect B cells and epithelial cells, although there are now reports of EBV infection in normal T cells and neoplastic T-cell diseases. In patients with human immunodeficiency virus (HIV) infection, EBV is associated with the benign epithelial lesion, hairy leukoplakia, and has been reported in up to 80% of acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma. This study shows the presence of EBV in malignant oral T-cell lymphoma in three AIDS patients, two of whom had concurrent manifestation of hairy leukoplakia. The T-cell lineage of the tumor cells was determined by positive immunophenotyping for T-cell markers and lack of B-cell or nonhematopoietic (cytokeratin) determinants. All tumors contained monoclonal T-cell populations shown by polymerase chain reaction, which showed amplification of T-cell receptor gamma chain DNA without evidence of Ig heavy chain gene rearrangement. Furthermore, these lesions showed the presence of EBV DNA and expression of EBV latent gene products in the tumor cells. EBV involvement in AIDS-related T-cell lymphoma has not been widely reported and may represent a further manifestation of opportunistic EBV infection arising in the HIV-immunocompromised host.

Acquired Immunodeficiency Syndrome↗