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Biomedical subjects

A J Mighell

Publications and source records attributed to A J Mighell.

17 recordsLinked to original sources
PubMed2000

Vertebrate pseudogenes.

Pseudogenes are commonly encountered during investigation of the genomes of a wide range of life forms. This review concentrates on vertebrate, and in particular mammalian, pseudogenes and describes their origin and subsequent evolution. Consideration is also given to pseudogenes that are transcribed and to the unusual group of genes that exist at the interface between functional genes and non-functional pseudogenes. As the sequences of different genomes are characterised, the recognition and interpretation of pseudogene sequences will become more important and have a greater impact in the field of molecular genetics.

Animals↗
PubMed1998

An overview of the complexities and subtleties of immunohistochemistry.

Immunohistochemistry has the potential to be a powerful research tool. However, immunohistochemical studies are frequently undertaken without regard to the complexities and subtleties of these useful techniques. This review aims to address the problems and limitations that are often encountered, and the procedures that should be considered in both the planning and interpretation of immunohistochemical studies. Particular reference is made to the generation of functionally different protein isoforms from a single gene by alternative splicing and post-translational modifications, primary antibody selection, the effects of tissue manipulation such as fixation and antigen retrieval, the need for appropriate controls and interpretation of staining patterns.

Antibodies↗
PubMed1998

Histological identification of carcinoma in 21 gauge needle tracks after fine needle aspiration biopsy of head and neck carcinoma.

Six cancer resection specimens were thoroughly sectioned and microscopically examined at areas known to have been around 21 gauge fine needle aspiration (FNA) biopsy sites, in an attempt to identify needle tracks. All cases had an interval of not less than 10 days between FNA biopsy and surgery. Foci of tumour were identified histologically in needle tracks from two patients with carcinoma. This is the first instance, outside of experimental animal models, of histologically confirmed, viable tumour spread in FNA biopsy tracks. Although this complication is not common and is of unknown clinical significance, it is one that all clinicians who undertake FNA of malignant neoplasms should be aware of.

Adenocarcinoma↗
PubMed1997

Alu sequences.

Alu sequences are frequently encountered during study of human genomic nucleic acid and form a major component of repetitive DNA. This review describes the origin of Alu sequences and their subsequent amplification and evolution into distinct subfamilies. In recent years a number of different functional roles for Alu sequences have been described. The multiple influences of Alu sequences on RNA polymerase II-mediated gene expression and the presence of Alu sequences in RNA polymerase III-generated transcripts are discussed.

Cell Nucleus↗
PubMed1997

Human tenascin-C: identification of a novel type III repeat in oral cancer and of novel splice variants in normal, malignant and reactive oral mucosae.

Tenascin-C is a mosaic, linear glycoprotein that is up-regulated during many normal and pathological processes involving either cell migration or tissue morphogenesis, such as invasion of malignant cells and wound healing. Human tenascin-C contains 8 consecutive type III fibronectin (TNCfn) domains that are involved in alternative splicing and potentially generate a large number of isoforms that code for tenascin-C proteins with subtly different functions. Human tenascin-C splice variants were investigated by RT-PCR in a range of normal and pathological oral mucosal tissues. A novel, 9th human TNCfn domain involved in alternative splicing was identified. It shares 70% nucleic acid and 55% protein sequence homology with chicken TNCfn-ad2. As in avians, this novel repeat was located between TNCfn-B and TNCfn-ad1 and accordingly was designated human TNCfn-ad2. Human TNCfn-ad2 was detected in only 2 of 10 oral cancers. However, TNCfn-ad2 was absent from 40 normal, reactive, pre-malignant and other oral mucosal specimens investigated. Previous studies have described 8 splice variant transcripts for human tenascin-C. By systematic investigation we identified further novel splice variants for human tenascin-C. Furthermore, our results indicate that many potential splice variants probably do not exist in the tissues investigated. Thus, we have demonstrated that human tenascin-C transcripts generate a complex but selected repertoire of different alternative splice products.

Alternative Splicing↗
PubMed1997

RT-PCR investigation of fibronectin mRNA isoforms in malignant, normal and reactive oral mucosa.

This study aimed to establish patterns of cellular fibronectin mRNA splice variants in normal oral mucosa, oral squamous cell carcinoma, oral leukoplakias with and without atypia, and focal reactive overgrowths of oral mucosa. Particular emphasis was placed on evaluation of either the EDA or EDB domains as markers of malignancy. Total RNA was extracted from normal oral mucosa, oral squamous cell carcinoma, oral leukoplakias with and without atypia, reactive epulides, fibroepithelial polyps and denture-related hyperplasia. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to identify different fibronectin transcripts at three splice sites (EDA, EDB and IIICS). All the tissues investigated produced EDA+, EDA-, EDB+ and EDB- splice variants, and this study did not support RT-PCR-based detection of either EDA or EDB domains as markers of malignancy in oral tissues. Variations in IIICS splice patterns were observed, although these were not specific to any lesion group. In particular, there were differences in either the inclusion or omission of the domain coding for the CS-5 binding site for alpha 4 beta 1 integrin, whereas the CS-1 binding site for alpha 4 beta 1 integrin was typically present when additional domains were included at the IIICS splice site. In conclusion, complex patterns of fibronectin splice variant transcripts exist in normal and pathological oral mucosa. This may reflect the multiple biological functions identified for fibronectin proteins, although the significance of different specific fibronectin splice variants has yet to be fully elucidated.

Alternative Splicing↗
PubMed1997

Histochemical and immunohistochemical localisation of elastic system fibres in focal reactive overgrowths of oral mucosa.

Eight specimens each of the following groups were investigated: gingival pyogenic granuloma, fibrous epulis, calcifying fibrous epulis, peripheral giant cell granuloma, giant cell fibroma (four gingival, four non-gingival), denture-irritation hyperplasia and fibroepithelial polyp. These lesions have diverse histopathological appearances but the composition of their connective tissue is poorly defined. The elastic system consists of a complex mixture of glycoproteins that in normal oral mucosa form three differentially distributed fibre types; oxytalan, elaunin and elastic. The elastic system was investigated by Verhoeff's haematoxylin stain, aldehyde fuchsin staining and an anti-elastin monoclonal antibody. Elastin was identified in all fibroepithelial polyps and denture-irritation hyperplasias, but in none of the other lesions. In particular, this identified a distinct difference in the extracellular matrix between the giant cell fibroma and fibroepithelial polyp. Many of the epulides included only oxytalan fibres, but the presence of oxytalan fibres did not follow any pattern within either a single lesion group, or between different lesions. However, the presence of oxytalan fibres in the absence of elastin does not necessarily support a periodontal ligament origin for reactive epulides.

Antibodies, Monoclonal↗
PubMed1996

Immunolocalisation of tenascin-C in focal reactive overgrowths of oral mucosa.

Focal reactive overgrowths of oral mucosa were investigated in the following groups: gingival pyogenic granuloma, fibrous epulis, calcifying fibrous epulis, peripheral giant cell granuloma, giant cell fibroma, fibroepithelial polyp and denture-related fibrous hyperplasia (n = 8 for each group). We hypothesised that immunoreactivity to tenascin-C, a functional protein associated with connective tissue organisation and cell migration, would be differentially distributed in individual lesions and between lesion groups. Staining patterns for giant cell fibromas and fibroepithelial polyps were similar to those reported for normal mucosa. By contrast, additional staining was observed in the other lesion groups, although immunoreactivity was variable and not specific to each lesion group. Strong immunoreactivity was observed around blood vessels lined with plump endothelial cells and in regions where keratinocytes were migrating over ulcerated surfaces. Interlacing collagenous fascicles could be either strongly or weakly immunoreactive, with either fibrillar or diffuse staining. Localised staining was observed around, but not within, areas of calcification.

Blood Vessels↗
PubMed1996

PCNA and Ki-67 immunoreactivity in multinucleated cells of giant cell fibroma and peripheral giant cell granuloma.

Immunohistochemical investigation of PCNA and Ki-67, two diverse nuclear proteins essential to the cell cycle, was undertaken in archival, formalin-fixed and paraffin-embedded specimens of giant cell fibroma (GCF) and peripheral giant cell granuloma (PGCG++). GCF multinucleated cell nuclei were mostly PCNA+, although there was variability in staining intensity. This indicates heterogeneity in nuclear PCNA metabolism of GCF multinucleated cells, and it is possible that the most intensely stained nuclei have passed through the cell cycle more recently compared to the less immunoreactive nuclei. However, the absence of Ki-67 immunoreactivity in GCF multinucleated cells, and absence of mitoses in GCF multinucleated cells, suggests that cell cycling in the absence of cytokinesis is not involved in GCF multinucleated cell formation. Alternatively, GCF multinucleated cells possibly form by fusion of mononuclear cells previously identified as fibroblasts, although this theory cannot be confirmed by the data presented in this study, and the histogenesis of GCF multinucleated cells remains unclear. In contrast, absence of either PCNA or Ki-67 immunoreactivity in PGCG multinucleated cells is consistent with an osteoclast lineage and formation from differentiated mononuclear cells.

Cell Cycle↗
PubMed1996

Sebaceous carcinoma of the parotid gland.

A report of an 87-year-old Caucasian female with an extensive sebaceous carcinoma of the parotid gland is presented. The computed tomographic characteristics of this rare neoplasm are reported for the first time.

Adenocarcinoma, Sebaceous↗
PubMed1995

Acceptance and perception of percutaneous endoscopic gastrostomy by patients with upper aerodigestive tract cancer.

Surgeons have identified a role for percutaneous endoscopic gastrostomy (PEG) in selected patients with upper aerodigestive tract cancer, but little is known about the patient's acceptance and perception of PEG. Nineteen patients with upper aerodigestive tract cancer had placement of a PEG and were asked about their perceptions via a series of descriptors and associated questions. The 13 patients who had PEG placement under local anaesthesia and intravenous midazolam were questioned 12-16 h later and reported that the procedure was comfortable and not as bad as expected. These patients together with a further 6 patients who had placement under general anaesthesia were questioned about their acceptance of the PEG tube after 10 days. Comfort, ease of use and maintenance, and coverage by clothing confirms that PEG is an acceptable delivery system for enteral nutrition in patients with upper aerodigestive tract cancer.

Adult↗
PubMed1995

Peripheral giant cell granuloma: a clinical study of 77 cases from 62 patients, and literature review.

OBJECTIVES: The aim of this study was to identify the principle clinical features of the peripheral giant cell granuloma (PGCG), and to recognise clinical features of PGCG that are poorly defined. DESIGN: We reviewed retrospectively 77 cases of PGCG from 62 patients, from our files with respect to incidence, sex, patient age, race, clinical symptoms and signs, radiographic features and recurrence following excision. RESULTS AND CONCLUSIONS: Our results were largely in agreement with previous reports, although there is wide variation in the results published between series. In addition, some clinical features of PGCG are poorly defined. Little is known about the relative incidences of PGCG and central giant cell granuloma. An association between PGCG and tooth loss may exist, but is poorly defined, and not all PGCG that involve edentulous areas follow recent tooth loss. Information about PGCG recurrence after excision is limited, and does not necessarily follow incomplete excision. Despite the large number of reported cases of PGCG, clarification of some clinical features is required, and may help formulation and interpretation of future laboratory-based research into this poorly understood lesion.

Adolescent↗
PubMed1995

Patterns of immunoreactivity to an anti-fibronectin polyclonal antibody in formalin-fixed, paraffin-embedded oral tissues are dependent on methods of antigen retrieval.

The influence of antigen retrieval (AR) technique on immunoreactivity in formalin-fixed, paraffin-embedded tissues is recognized. In focal reactive overgrowths of oral mucosa, we noted that patterns of immunoreactivity to a fibronectin polyclonal antibody were dependent on methods of AR. To establish these patterns we investigated eight pyogenic granulomas and eight fibroepithelial polyps. In the absence of AR no immunoreactivity was observed. After alpha-chymotrypsin AR a band of intense immunoreactivity was associated with vascular endothelial cells, with either minimal or no staining of connective tissue. After microwave AR immunoreactivity was observed in connective tissue, especially in the subepithelial region, but there was no specific vascular staining. After autoclave AR immunoreactivity was observed in connective tissue and also in epithelial nuclei. To determine if these results represented either changes induced by tissue fixation and processing or exposure of epitopes normally masked in vivo, we investigated frozen sections from two fibroepithelial polyps and one pyogenic granuloma. In frozen sections immunoreactivity was observed around vascular endothelial cells and within connective tissue, especially in the subepithelial region, but not in epithelia. This study provides indirect evidence that alpha-chymotrypsin and heat-mediated AR protocols expose different masked epitopes, and reinforces the need to undertake appropriate pilot studies for immunohistochemical investigation of archival tissue.

Antibodies↗
PubMed1994

Meningioma--an unusual forehead swelling: a case report.

Meningiomas are rarely encountered by head and neck clinicians. This report describes a patient with a meningioma presenting uncommonly as a long-standing forehead mass with minimal symptoms. Investigation identified a large bifrontal meningioma with extra-cranial extension involving the right orbit and forehead. The literature is reviewed with particular reference to extra-cranial meningioma and the case is discussed.

Aged↗
PubMedDate not supplied

Periosteal fasciitis of the mandible.

BACKGROUND: Periosteal fasciitis is rare in the head and neck. We believe only two cases of fasciitis-induced erosion through the mandibular cortical plate have previously been reported. RESULTS: Management of a case of periosteal fasciitis with bone erosion at the mandibular angle is reported in a 38-year-old man. CONCLUSIONS: Misdiagnosis of fasciitis in the past has led to inappropriate management and unnecessary morbidity. The principles of diagnosis and management of this unusual and confusing disorder are highlighted.

Adult↗