Publications by authors named "Alec High"

Background: The aim of this study was to investigate the influence of sodium chloride (NaCl) content in electrolyte solution on electrochemical impedance measurements of human dentin by employing electrochemical impedance spectroscopy.

Materials And Methods: Dentin samples were prepared from extracted molars. Electrochemical impedance measurements were carried out over a wide frequency range (0.

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The study of the relationships between pre-cancer and cancer and identification of early driver mutations is becoming increasingly important as the value of molecular markers of early disease and personalised drug targets is recognized, especially now the extent of clonal heterogeneity in fully invasive disease is being realized. It has been assumed that pre-cancerous lesions exhibit a fairly passive progression to invasive disease; the degree to which they, too, are heterogeneous is unknown. We performed ultra-deep sequencing of thousands of selected mutations, together with copy number analysis, from multiple, matched pre-invasive lesions, primary tumours and metastases from five patients with oral cancer, some with multiple primary tumours presenting either synchronously or metachronously, totalling 75 samples.

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Aim: The aim of this study was to characterise plasma cell infiltrates, in terms of IgG4 positivity, in specific and non-specific plasma cell-rich chronic inflammatory conditions of the oral mucosa. Exploring the possibility that specific plasma cell-rich oral inflammatory conditions have association with or represent an oral manifestation of immunoglobulin G4-related disease (IgG4-RD).

Methods: Ten patients with plasma cell-rich chronic inflammatory conditions of the oral mucosa were identified (seven--plasma cell mucositis and three--non-specific diffuse oral mucosal inflammation with ulceration).

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Verrucous carcinoma of the oral cavity (OVC) is considered a subtype of classical oral squamous cell carcinoma (OSCC). Diagnosis is problematic, and additional biomarkers are needed to better stratify patients. To investigate their molecular signature, we performed low-coverage copy number (CN) sequencing on 57 OVC and exome and RNA sequencing on a subset of these and compared the data to the same OSCC parameters.

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Objective: The etiology of oral verrucous carcinoma is unknown, and human papillomavirus 'involvement' remains contentious. The uncertainty can be attributed to varied detection procedures and difficulties in defining 'gold-standard' histologic criteria for diagnosing 'verrucous' lesions. Their paucity also hampers investigation.

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Background: Human papilloma virus is a risk factor for oropharyngeal cancer. Evidence for a similar aetiological role in the development of oral dysplasia or its transformation to oral cancer is not as clear. Meta-analyses estimate the prevalence of high-risk human papilloma virus (HPV) serotypes to be three times higher in pre-malignant lesions and cancer than in normal oral mucosa.

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HHARI (also known as ARIH1) is an ubiquitin-protein ligase and is the cognate of the E2, UbcH7 (UBE2L3). To establish a functional role for HHARI in cellular proliferation processes, we performed a reverse genetics screen that identified n=86/522 (16.5%) ubiquitin conjugation components that have a statistically significant effect on cell proliferation, which included HHARI as a strong hit.

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BACKGROUND.  Hypophosphatasia (HP) is characterized by defective mineralization of bone and teeth because of deficient alkaline phosphatase activity. There are generally six recognized clinical forms, of which the most severe is often lethal prenatally or early in life.

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Human papillomavirus (HPV) infection in cases of squamous cell carcinoma of the oropharynx is a powerful predictive and prognostic biomarker. We describe how the use of next-generation sequencing can provide a novel method for the detection of HPV in DNA isolated from formalin-fixed paraffin-embedded tissues. Using this methodology in a cohort of 44 head and neck tumors, we identified the samples that contained HPV sequences, the viral subtype involved, and a direct readout of viral load.

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Background:  Non-setting calcium hydroxide (Ultracal XS(®) ) is recommended by the International Association of Dental Traumatology as the initial medicament following avulsion and replantation for mature teeth. There is experimental evidence to suggest Ledermix(®) , placed as an alternative inter-visit dressing may improve periodontal healing.

Aim:  This study investigated, using a multi-centre randomized controlled trial, the effect of two root canal medicaments, Ledermix(®) and Ultracal XS(®) , on periodontal healing of avulsed and replanted teeth.

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Introduction: There is evidence to suggest that Ledermix, placed as an intervisit root canal dressing, might improve periodontal healing after replantation of avulsed teeth. As a part of a multicenter randomized controlled trial, we aimed to compare the effect of 2 root canal medicaments, Ledermix and Ultracal XS, on the discoloration of replanted teeth.

Methods: Discoloration was investigated by using 3 methods: patient satisfaction with the color of replanted teeth, clinical photographs taken at baseline and 12-month reviews, and estimation of color change by using CIELAB scores for baseline and 12-month photographs.

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In recent years there has been much interest in the use of optical diagnostics in cancer detection. Early diagnosis of cancer affords early intervention and greatest chance of cure. Raman spectroscopy is based on the interaction of photons with the target material producing a highly detailed biochemical 'fingerprint' of the sample.

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Long PLUNC1 (LPLUNC1, C20orf114) is a member of a family of poorly described proteins (PLUNCS) expressed in the upper respiratory tract and oral cavity, which may function in host defence. Although it is one of the most highly expressed genes in the upper airways and has been identified in sputum and nasal secretions by proteomic studies, localisation of LPLUNC1 protein has not yet been described. We developed affinity purified antibodies and localised the protein in tissues of the human respiratory tract, oro- and nasopharynx.

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Raman spectroscopy could offer non-invasive, rapid and an objective nature to cancer diagnostics. However, much work in this field has focused on resolving differences between cancerous and non-cancerous tissues, and lacks the reproducibility and interpretation to be put into clinical practice. Much work is needed on basic cellular differences between malignancy and normal.

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Cancer poses a massive health burden with incidence rates expected to double globally over the next decade. In the United Kingdom screening programmes exists for cervical, breast, and colorectal cancer. The ability to screen individuals for solid malignant tumours using only a peripheral blood sample would revolutionise cancer services and permit early diagnosis and intervention.

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We recently described the Palate Lung Nasal Clone (PLUNC) family of proteins as an extended group of proteins expressed in the upper airways, nose and mouth. Little is known about these proteins, but they are secreted into the airway and nasal lining fluids and saliva where, due to their structural similarity with lipopolysaccharide-binding protein and bactericidal/permeability-increasing protein, they may play a role in the innate immune defence. We now describe the generation and characterisation of novel affinity-purified antibodies to SPLUNC2, and use them to determine the expression of this, the major salivary gland PLUNC.

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Actinomycosis is a slowly progressive infection that can occur anywhere in the body. Three distinct clinical entities are described: cervico-facial, abdomino-pelvic and thoracopulmonary. Actinomyces are anaerobic, gram positive, non-acid-fast, branched filamentous bacteria that form part of the normal oral, colonic and vaginal flora of humans.

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Non-destructive methods, such as the ac-impedance technique, have recently been applied to early caries detection and to identify micro-leakage between tooth structure and filling materials. However, in vitro impedance measurements are affected by a number of external factors. The purpose of present study was to investigate the effect of the age of teeth on impedance measurements of human dentine by employing electrical impedance spectroscopy (EIS).

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Background: The Whey Acidic Protein domain is an evolutionarily conserved motif found in a number of proteins, the best studied of which are antiproteinases involved in the innate immune defence of multiple epithelia. We recently characterised the WFDC2 gene which encodes a two WAP domain-containing protein, initially suggested as a marker for epididymis, and showed that it is highly expressed in the lung and salivary gland. The precise location of WFDC2 protein in these sites has not been described.

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Objectives: To identify histological features that distinguish amalgam-associated oral lichenoid reactions (AAOLR) from oral lichen planus (OLP).

Methods: Oral pathologists provided their opinion as to the possibility of distinguishing AAOLR and OLP histologically, the features important in distinguishing AAOLR from OLP and the diagnosis of 12 AAOLR and 12 OLP cases including the features that drew them to their conclusion.

Results: There was considerable variation between pathologists in their ability to distinguish the AAOLR and OLP cases.

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Purpose Of Review: Basal cell nevus syndrome (BCNS), is a hereditary condition transmitted as an autosomal dominant trait exhibiting high penetrance and variable expressivity. Inherited or spontaneous mutations in the human homologue of the Drosophila patched gene underlie the disorder and in addition to tumor predisposition, are associated with a range of 'patterning' defects. Recent advances, with glimpses of possible therapies are emerging, but because of the wide-ranging nature of phenotypic expression and overlap with other syndromes, there is difficulty.

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Short PLUNC1 (SPLUNC1) is the founding member of a novel family of proteins (PLUNC) expressed in the upper respiratory tract that may function in host defence. It is one of the most highly expressed genes in the upper airways and the protein has been detected in sputum and nasal secretions. This study describes, for the first time, the precise cellular localization of SPLUNC1 in human tissues from the respiratory tract.

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Objective: To analyse smear layers on human dentine using ac-impedance spectroscopy.

Methods: Dentine samples were prepared from extracted, sound, third molars. Impedance measurements were carried out on dentine samples before and after etching.

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In 1960, Robert James Gorlin and William Goltz, both American physicians, defined a new syndrome. Little did they realize that 40 years later, the pathways involved in its development would be provoking serious and sustained interest amongst a plethora of specialists. Fruit-fly biologists, oncologists, geneticists, dermatologists, indeed, hardly a medical or dental specialist gets excluded.

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