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Biomedical subjects

J Nunn

Publications and source records attributed to J Nunn.

At least 19 recordsLinked to original sources
PubMed2003

Allelic imbalance at the DNA mismatch repair loci, hMSH2, hMLH1, hPMS1, hPMS2 and hMSH3, in squamous cell carcinoma of the head and neck.

BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) is one of the 10 most frequently occurring cancers in the world. Defective mismatch repair, as exhibited by the phenomenon of microsatellite instability, has been observed in SCCHN although no reports of mismatch repair gene mutations or altered protein expression have been published. In a variety of microsatellite instability (MSI) positive cancers where mutations in the mismatch repair (MMR) genes were not observed, allelic imbalance at the loci of the MMR genes was prevalent. OBJECTIVE: To investigate whether allelic imbalance at the MMR genetic loci contributes to the development of SCCHN. MATERIALS AND METHODS: 35 matched normal/tumour SCCHN pairs were studied using 29 microsatellite markers located within and adjacent to six known DNA mismatch repair genes. In addition, mutational analysis and protein expression of hMSH2 and hMLH1 were investigated. RESULTS AND CONCLUSIONS: We demonstrated that 36 and 17% of the analysed SCCHN specimens exhibited allele imbalance at the hMLH1 and hMSH3 genetic loci, respectively. Allelic instability at these two loci was found to be correlated with the MSI status of the SCCHN tumours. Allelic instability was found to be uncommon at the other MMR gene loci analysed. One mutation was found in hMSH2 and none in hMLH1 in this series of tumours. 23 of 24 (96%) of the examined SCCHN tumours showed reduced expression of either hMSH2 or hMCH1 genes. Allelic instability in the MMR genes, hMLH1 and hMSH3, is proposed to be involved in the aetiology of SCCHN tumours.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Decreased endothelin receptor B expression in large primary uveal melanomas is associated with early clinical metastasis and short survival.

The most devastating aspect of cancer is the metastasis of tumour cells to organs distant from the original tumour site. The major problem facing oncologists treating uveal melanoma, the most common cancer of the eye, is metastatic disease. To lower mortality, it is necessary to increase our understanding of the molecular genetic alterations involved in this process. Using suppression subtractive hybridisation, we have analysed differential gene expression between four primary tumours from patients who have developed clinical metastasis and four primary tumours from patients with no evidence of metastasis to date. We have identified endothelin receptor type B as differentially expressed between these tumours and confirmed this observation using comparative multiplex RT-PCR. In a further 33 tumours, reduced endothelin receptor type B expression correlated with death from metastatic disease. Reduced expression also correlated with other known prognostic indicators, including the presence of epithelioid cells, chromosome 3 allelic imbalance and chromosome 8q allelic imbalance. Endothelin receptor type B expression was also reduced in four out of four primary small cell lung carcinomas compared to normal bronchial epithelium. We also show that the observed down-regulation of endothelin receptor type B in uveal melanoma was not due to gene deletion. Our findings suggest a role for endothelin receptor type B in the metastasis of uveal melanoma and, potentially, in the metastasis of other neural crest tumours.

Adult↗
PubMed2001

Schizotypy and patterns of lateral asymmetry on hemisphere-specific language tasks.

Following the notion that abnormalities of hemispheric asymmetry may underlie schizophrenia, patterns of cognitive hemispheric asymmetries, as assessed by left and right hemisphere language tasks, were examined in relation to schizotypal symptoms. Ninety right-handed undergraduates completed the Oxford-Liverpool Inventory of Feelings and Experiences questionnaire (O-LIFE; Mason, O., Claridge, G., Jackson, M., 1995. New scales for the assessment of schizotypy. Personality and Individual Differences, Vol. 53, pp. 727-730), which measures different aspects of schizotypy symptomatology. Low scores on right, but not left, hemisphere language tasks were significant predictors of high scores on positive schizotypal symptomatology scales (Unusual Experiences and the STA) over and above the contributions of the left hemisphere language tasks and demographic variables. Low scores on both left and right hemisphere language tasks were significant predictors of high scores on the Cognitive Disorganisation factor, over and above the contributions of tasks related to the contralateral hemisphere and demographic variables. Neither the right nor the left hemisphere language tasks resulted in a significantly good degree of prediction of introvertive anhedonia (an index of negative schizotypal symptomatology) or impulsive non-conformity. The findings provide partial support for some current theories of hemispheric differences in schizophrenia and schizotypy.

Adult↗
PubMed2001

Dental attendance in 1998 and implications for the future.

The 1998 survey of Adult Dental Health in the UK was carried out under the auspices of the Office of National Statistics together with the Universities of Birmingham, Dundee, Newcastle-upon-Tyne and Wales. A key behavioural indicator in these decennial surveys is whether people say they go to a dentist for a regular dental check-up, an occasional dental check-up or only when they have trouble with their teeth. The proportion of dentate adults in the UK who report attending for regular dental check-ups has risen from 43% in 1978 to 59% in 1998. Older adults (over 55 years old) in 1998 were the most likely to say they attend for regular dental check-ups. Many younger adults (16-24) in 1998 said they went to a dentist less often than 5 years previously, they were also the least likely to say they attend for regular dental check-ups. Dental anxiety remains a problem for many dental patients but another factor of importance to many is their want to be involved in the treatment process and especially to be given an estimate of treatment costs.

Adolescent↗
PubMed2001

Loss of heterozygosity on chromosomes 3, 9, 13, and 17, including the retinoblastoma locus, in uveal melanoma.

PURPOSE: To identify tumor-suppressor loci that may contribute to the pathogenesis of uveal melanoma. METHODS: Multiplex fluorescence microsatellite assays were performed on 27 uveal melanomas using markers at 3p25-p26, 3p14.2, 9p21-p23, 13q14, 13q12.3-q13, and 17p13, close to or within the von Hippel Lindau (VHL), fragile histidine triad (FHIT), p16/cyclin-dependent kinase inhibitor 2 (CDKN2A), retinoblastoma (RB1), breast cancer 2 (BRCA2), and p53 tumor suppressor loci, respectively. Further markers on chromosomes 3 and 9 were analyzed individually. RESULTS: Loss of heterozygosity (LOH) was identified in 63% of tumors, most frequently on chromosome 3 (52%), in association with epithelioid cells (P = 0.0002) and microvascular loops (P = 0.0008). In the majority of cases, LOH on chromosome 3 was detected at all informative markers. The second most common alteration was LOH at an RB1 intragenic marker (21% tumors), with retention of a more centromeric 13q marker (near BRCA2). The pattern of LOH on chromosome 9p was consistent with the involvement of a region telomeric to CDKN2A. LOH at TP53 was infrequent. CONCLUSIONS: In the majority of cases, chromosome 3 LOH involves an entire chromosome homologue, which hampers identification of the relevant suppressor loci. This LOH correlates with the presence of microvascular loops and epithelioid cells, two of the recognized histologic indicators of poor prognosis. Data for chromosomes 13 and 9 support a role for RB1 in the pathogenesis of uveal melanoma but also raise the possibility of the involvement of additional loci close to RB1 and CDKN2A.

Acid Anhydride Hydrolases↗
PubMed2000

The condition of teeth in the UK in 1998 and implications for the future.

The latest of the decennial surveys of the United Kingdom was undertaken in 1998 by the Office of National Statistics in collaboration with the dental schools of the Universities of Birmingham, Dundee, Newcastle and Wales. Dentate adults in 1998 have fewer missing teeth and more sound and untreated teeth on average than in 1978. The average number of decayed teeth has dropped significantly from 1.9 in 1978 to 1.1 in 1998. The average number of filled teeth has remained fairly constant over the same time but its distribution has changed quite markedly towards older adults having more filled teeth than people of a similar age in the past whilst the reverse is true for younger adults. The overall trends are encouraging, but there is a need to review the way disease is managed in adults in the United Kingdom.

Adolescent↗
PubMed1999

Fractional allele loss indicates distinct genetic populations in the development of squamous cell carcinoma of the head and neck (SCCHN).

Loss of heterozygosity (LOH) had been widely used to assess genetic instability in tumours and a high LOH on chromosome arms 3p, 9p and 17p has been considered to be a common event in squamous cell carcinoma of the head and neck (SCCHN). We have investigated LOH in 52 SCCHN using a range of microsatellite markers. LOH was observed in 69% of individuals on 17p using seven markers, in 64% of individuals on 3p using 17 markers and in 61% of individuals on 9p using 11 markers. Fractional allele loss (FAL) has been calculated for each tumour (FAL is the number of chromosomal arms showing LOH divided by the number of informative chromosomal arms) and a median FAL value of 0.25 was obtained in the 52 SCCHN studied. The LOH data were examined on the basis of FAL scores: low FAL (LFAL), 0.00-0.19; medium FAL (MFAL), 0.20-0.32; high FAL (HFAL), 0.33-0.88. HFAL tumours demonstrated a significantly higher LOH on chromosome arms 3p, 9p and 17p, with 94% LOH on 3p, 94% on 9p and 100% on 17p compared with LFAL tumours. Six of the 16 patients in the LFAL group were found to have no LOH on 3p, 9p or 17p and of these four had LOH at other sites, on chromosomes 2p25-p24, 5q21-22, 7pter-p22, 8q13-q22.1, 11q23.3, 13q32, 17q, 18p11.21, 18q21.31 and 19q12-q13.1. These results indicate that LFAL patients form a subset of SCCHN tumours with distinct molecular initiating events which may represent a discrete genetic population.

Alleles↗
PubMed1999

Views of parents and head teachers on the school dental screening service in a north of England city.

OBJECTIVE: The study was designed to explore parents' and head teachers' understanding of and attitudes to the process, objectives and perceived outcomes of a school dental screening. BASIC RESEARCH DESIGN: Qualitative methods were used as a source for questionnaire development and questionnaires were subsequently used to test the strength of agreement with the qualitative findings. PARTICIPANTS: Head teachers and parents of a sample of 5- and 10-year-old children attending primary schools in Sunderland. RESULTS: Questionnaire responses from 83 (79%) of the head teachers and 934 (82%) parents of 5- and 10-year-old children showed that the exercise was well accepted by the majority. Gaps were identified in many aspects of communication between the Community Dental Service, schools and parents. CONCLUSIONS: It is recommended that, taking into account the views of all involved, the objectives of the exercise should be clearly defined and then clearly communicated. Evaluation should follow, measuring the extent to which the defined objectives are met. In this way the process will make a more positive and relevant contribution to oral health and the provision of primary dental care.

Adult↗
PubMed1998

The Knights of the Round Table hypothesis of tumour suppressor gene function--noble sacrifice or sexual dalliance: genes, including p53, BRCA1/2 and RB have evolved by horizontal and vertical transmission of mating factor genes and are involved in gametogenesis, implantation, development and tumourigenesis.

The genes involved in negative cell cycle regulation and familial tumour susceptibility including APC, BRCA, p53, RB, WT1 are unique and have no homologies with other genes. Our hypothesis suggests they originated from mating factor genes, which halted cell division in response to stress to generate genetic diversity by sexual mechanisms. Some have evolved principally by vertical transmission (mismatch repair), others by horizontal transmission via mobile elements, predominantly in oocytes. We demonstrate amplification in human extra-embryonic tissues in fetus and mother in implantation; in the developing fetus, differing tissue-specific patterns are seen, especially between testis and ovary. We suggest that the fetus is susceptible to maternal transmission of infections including CMV, malaria, trypanosomes, whose sequences occur within these genes. In head and neck cancers, we demonstrate specific patterns of loss or instability involving up to seven different TSG. We suggest mechanisms of tumourigenesis involve transposable elements and episome formation, leading to loss of negative cell cycle regulation and exit from G0.

Animals↗
PubMed1997

Height and weight achievement in cleft lip and palate.

Growth was studied in 83 children with cleft lip and/or palate aged 0-4 years attending a specialist regional centre. Information was collected by a personal interview, postal questionnaire, and record review. The group as a whole grew relatively poorly in early infancy but subsequently recovered, attaining both expected weight and height by last follow up at age 25.5 months (range 3 to 47). However, the group proved heterogeneous, with children with isolated clefts of the secondary palate showing the most abnormal growth. Children with underlying syndromes were significantly more likely to be short at follow up, while type or severity of cleft was not significantly related to follow up height. Therefore, while cleft palate was associated with significant growth faltering in early infancy, rapid recovery took place following surgical repair and appears to have resulted in no residual growth deficit.

Body Height↗
PubMed1996

Tooth wear--dental erosion.

This article aims to address the issues arising out of the increasing concern by general dental practitioners of erosion-related tooth wear. The prevalence, common presentation, differential diagnosis, likely aetiology, prevention and management of suspected cases of this form of tooth wear are considered.

Adolescent↗
PubMed1996

Height and weight achievement in cleft lip and palate.

Growth was studied in 83 children with cleft lip and/or palate aged 0-4 years attending a specialist regional centre. Information was collected by a personal interview, postal questionnaire, and record review. The group as a whole grew relatively poorly in early infancy but subsequently recovered, attaining both expected weight and height by last follow up at age 25.5 months (range 3 to 47). However, the group proved heterogeneous, with children with isolated clefts of the secondary palate showing the most abnormal growth. Children with underlying syndromes were significantly more likely to be short at follow up, while type or severity of cleft was not significantly related to follow up height. Therefore, while cleft palate was associated with significant growth faltering in early infancy, rapid recovery took place following surgical repair and appears to have resulted in no residual growth deficit.

Body Height↗
PubMed1994

Cognitive deficits induced by global cerebral ischaemia: relationship to brain damage and reversal by transplants.

The CA1 and hilar fields of the hippocampus are highly vulnerable to lack of oxygen after interruption of blood flow to the brain. Severe anterograde memory loss, seen in a significant proportion of heart attack survivors, has been attributed to selective bilateral ischaemic damage to the hippocampus. Animal models of global ischaemia, induced by extracranial occlusion of the major ascending arteries, enable assessment of the neuropathological and functional consequences of transient interruption of cerebral blood flow, and can inform strategies to reduce or alleviate ischaemic brain damage. This review focuses firstly on the nature of cognitive deficits induced by global ischaemia, how far they are consistent with lesion-based accounts of hippocampal function, and the extent to which these deficits can be correlated with CA1 cell loss. The second focus of the review is to examine the limited evidence for graft-induced recovery of cognitive function in animals subjected to global ischaemia. Recent findings that grafted foetal cells from discrete hippocampal fields follow appropriate laminar routes to form functional connections with host neurons, and that growth factors protect cells from ischaemic damage, have suggested that CA1 or trophic grafts placed in the region of ischaemic CA1 cell loss might restore or protect this vulnerable sector, and reduce cognitive deficits.

Animals↗
PubMed1994

The use of aspirin in children under 12 years old attending a paediatric dentistry department in a dental hospital.

For several years it has been recommended that aspirin should be avoided in children under the age of 12 years because of the risk of Reye's Syndrome. In this study we investigated the reported use of analgesics among children who attended the Children's Department of the Dental Hospital in Newcastle upon Tyne. In addition the study also investigated the complaints that led to use of analgesics, the dose and frequency of administration of the analgesic, and past and current contact with medical services. Of 179 children investigated, 129 were under 12 years-old; of these 129 children under 12 years-of-age, 72 (56%) had taken an analgesic within the previous six months, 12 (17%) of whom took aspirin. Three of these children who had taken aspirin were reported to have had a serious illness in their lives, and would therefore have had significant contact with medical services. One-quarter of all children who had taken an analgesic did so for toothache. Inappropriate use of aspirin in children under 12 years-of-age indicates that health education about the possible risks of Reye's Syndrome needs to be improved.

Aspirin↗