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C Seymour

Publications and source records attributed to C Seymour.

At least 19 recordsLinked to original sources
PubMed2006

The effect of melanin on the bystander effect in human keratinocytes.

The influence of melanin on radiation-induced bystander effects has been studied. Melanin is known to be a natural substance with proved radioprotective properties in different organisms and cell lines. It is non-toxic and is effective against acute and chronic irradiation. The lower the radiation dose, the higher the relative impact of melanin protection. In this study influence of melanin on human keratinocytes (HPV-G cells) has been studied using the colony-forming assay. We have shown that bystander donor medium from 0.5 Gy irradiated cells when transferred to unirradiated cells, caused almost the same effect as direct irradiation. Melanin increased the colony-forming ability of bystander recipient cells when it was added into culture medium before irradiation. The effect of melanin added after irradiation was to produce less protection in both the directly irradiated and bystander medium treated groups. The absorption spectrum of the filtered medium is identical to one of the intact culture medium showing that melanin was not present in filtered medium. Thus, it cannot protect recipient cells but reduces the amount of the bystander effect. It is concluded that melanin added before irradiation effectively decreased the radiation dose. The reduction of the impact of the bystander signal on recipient cells when melanin was added to the donor medium after harvest but before filtration, may mean that the bystander signal has a physical component as melanin can absorb all types of physical energy.

Cell Communication↗
PubMed2006

The involvement of calcium and MAP kinase signaling pathways in the production of radiation-induced bystander effects.

Much evidence now exists regarding radiation-induced bystander effects, but the mechanisms involved in the transduction of the signal are still unclear. The mitogen-activated protein kinase (MAPK) pathways have been linked to growth factor-mediated regulation of cellular events such as proliferation, senescence, differentiation and apoptosis. Activation of multiple MAPK pathways such as the ERK, JNK and p38 pathways have been shown to occur after exposure of cells to radiation and a variety of other toxic stresses. Previous studies have shown oxidative stress and calcium signaling to be important in radiation-induced bystander effects. The aim of the present study was to investigate MAPK signaling pathways in bystander cells exposed to irradiated cell conditioned medium (ICCM) and the role of oxidative metabolism and calcium signaling in the induction of bystander responses. Human keratinocytes (HPV-G cell line) were irradiated (0.005-5 Gy) using a cobalt-60 teletherapy unit. The medium was harvested 1 h postirradiation and transferred to recipient HPV-G cells. Phosphorylated forms of p38, JNK and ERK were studied by immunofluorescence 30 min-24 h after exposure to ICCM. Inhibitors of the ERK pathway (PD98059 and U0126), the JNK pathway (SP600125), and the p38 pathway (SB203580) were used to investigate whether bystander-induced cell death could be blocked. Cells were also incubated with ICCM in the presence of superoxide dismutase, catalase, EGTA, verapamil, nifedipine and thapsigargin to investigate whether bystander effects could be inhibited because of the known effects on calcium homeostasis. Activated forms of JNK and ERK proteins were observed after exposure to ICCM. Inhibition of the ERK pathway appeared to increase bystander-induced apoptosis, while inhibition of the JNK pathway appeared to decrease apoptosis. In addition, reactive oxygen species, such as superoxide and hydrogen peroxide, and calcium signaling were found to be important modulators of bystander responses. Further investigations of these signaling pathways may aid in the identification of novel therapeutic targets.

Bystander Effect↗
PubMed2005

Analysis of cedar pollen time series: no evidence of low-dimensional chaotic behavior.

Much of the current interest in pollen time series analysis is motivated by the possibility that pollen series arise from low-dimensional chaotic systems. If this is the case, short-range prediction using nonlinear modeling is justified and would produce high-quality forecasts that could be useful in providing pollen alerts to allergy sufferers. To date, contradictory reports about the characterization of the dynamics of pollen series can be found in the literature. Pollen series have been alternatively described as featuring and not featuring deterministic chaotic behavior. We showed that the choice of test for detection of deterministic chaos in pollen series is difficult because pollen series exhibit [see text] power spectra. This is a characteristic that is also produced by colored noise series, which mimic deterministic chaos in most tests. We proposed to apply the Ikeguchi-Aihara test to properly detect the presence of deterministic chaos in pollen series. We examined the dynamics of cedar (Cryptomeria japonica) hourly pollen series by means of the Ikeguchi-Aihara test and concluded that these pollen series cannot be described as low-dimensional deterministic chaos. Therefore, the application of low-dimensional chaotic deterministic models to the prediction of short-range pollen concentration will not result in high-accuracy pollen forecasts even though these models may provide useful forecasts for certain applications. We believe that our conclusion can be generalized to pollen series from other wind-pollinated plant species, as wind speed, the forcing parameter of the pollen emission and transport, is best described as a nondeterministic series that originates in the high dimensionality of the atmosphere.

Cryptomeria↗
PubMed2005

Elevated G2 chromosomal radiosensitivity in Irish breast cancer patients: a comparison with other studies.

Previous studies have shown that a significant proportion of breast cancer patients exhibit elevated G2 chromosomal radiosensitivity in contrast to controls (approximately 40%). In this study, the G2 assay was applied to a small number of Irish breast cancer patients who were recorded as sporadic cases and they were compared with a control group to compare and contrast with the previous documented studies. Lymphocyte cultures were set up on whole blood samples and stimulated with phytohaemagglutinin. The cultures were irradiated 74 h later with 0.5 Gy gamma-radiation and cells were arrested in metaphase by treating the cultures with colcemid. The chromosomes were harvested and the aberrations scored per 100 metaphases to assign a G2 score. The assay was first carried out on four donor controls to estimate intra-individual variation and then ten controls for inter-individual variation to measure assay reproducibility. The G2 assay was then applied to 27 breast cancer patients. Good intrinsic assay reproducibility was observed in the coefficient of variation (CV) data in three out of four controls. Intra-individual variation was similar in three out of four of the donors (4.6 - 5.1%) with one donor showing a higher CV compared with the others (22.9%). Inter-individual variation was calculated at 30.5% for all controls. No significant difference was observed between intra- and inter-individual variation using the variance ratio F-test. A G2 radiosensitivity cut-off of 110 aberrations/100 metaphases was calculated from the controls, and from this 70.4% of breast cancer patients and 7.7% of controls were calculated as G2 radiosensitive. This proportion of G2-sensitive breast cancer patients is the highest recorded in studies to date. It is thought that the G2 radiosensitivity assay is a biomarker of breast cancer predisposition genes of low penetrance, suggesting the presence of these genes in the Irish breast cancer patients used in this study who were recorded as sporadic cases. A larger number of Irish patients would be required to consolidate these findings and be representative of the Irish breast cancer population.

Adult↗
PubMed2004

Investigation of short-range cedar pollen forecasting.

Pollen forecasting is of increasing interest as a way to help the general public avoid contact with allergy-inducing pollen. It was recently reported that the dynamics underlying pollen concentration series is very similar to that of low-dimensional deterministic chaos, thus opening up new avenues of development in local pollen forecasting. Our analysis of hourly cedar pollen series for two seasons showed evidence of a small degree of determinism underlying the pollen time-series dynamics. However, we could not confirm that our pollen series was generated by a low-dimensional chaotic system. The nearest-neighbor method using local constant prediction applied to hourly pollen forecasting with a 1-h lead time was effective for small to medium pollen variations, but failed to reproduce large and intermittent pollen bursts. The performance of the nearest-neighbor model was significantly improved by applying a nonlinear filter to the source dataset. Standard time-series techniques such as neural networks did not improve upon these results. The difficulty in fully characterizing and accurately forecasting the pollen series was thought to originate in the nonstationarity of the series and in the large and intermittent pollen bursts that were found to have no apparent time structure. Thus the dynamics of hourly pollen series is probably not strongly tied to a low-dimensional chaotic system.

Journal Article↗
PubMed2004

Access to education for children and young people with medical needs: a practitioner's view.

Recent estimates suggest that in any one year there are around 100,000 children who need to receive their education outside school because of illness or injury. This figure does not include the growing number of young people who cannot attend their own schools because of mental health difficulties. In November 2001, the Department for Education and Skills published statutory guidance which 'sets out minimum national standards for the education of children who are unable to attend school because of medical needs.' Christine Seymour, Headteacher of a hospital school and home tuition service in a large, rural county and Chairperson of the National Association of Hospital and Home Teachers, examines how this guidance can assist in raising educational standards and removing barriers to achievement for this group of vulnerable children. She begins by summarizing the developments over the past decade which led to the statutory guidance and sets the document in the context of the Social Inclusion agenda. She explores the potential impact of such guidance on current and future practice from a practitioner's viewpoint, drawing on experiential observation and case study material to provide illustrative evidence.

Adolescent↗
PubMed2004

Ionizing radiation induces a stress response in primary cultures of rainbow trout skin.

Fish skin is very vulnerable to damage from physical and chemical pollutants because it is in direct contact with the aquatic environment. In this study, the effect of gamma radiation on primary cultures of rainbow trout skin was investigated. Primary cultures containing two cell types, epidermal cells and goblet mucous cells, were exposed to doses ranging from 0.5-15 Gy 60Co gamma radiation. Expression of PCNA, c-myc and BCL2 was investigated as well as growth and levels of apoptosis and necrosis. Morphological and functional changes were also studied. The irradiated cultures showed evidence of a dose-dependent increase in necrosis and enhanced proliferation as well as morphological damage. In addition, mucous cell area was found to decrease significantly after irradiation. The study shows the value of these primary cultures as in vitro models for studying radiation effects. They provide an effective alternative to whole-animal exposures for radiation risk assessment.

Animals↗
PubMed2001

Radiation-induced bystander effects: past history and future directions.

There has been a recent upsurge of interest in the phenomenon now known as radiation-induced bystander effects. This is largely due to the increased awareness of the contribution of indirect and delayed effects, such as genomic instability, to cellular outcomes after low-dose exposures. It is also due to the availability of tools such as the microbeam and advanced cell culture systems and to the ability to study end points such as gene or protein expression at low doses which were previously difficult to study. This review looks at the history of bystander effects in the earlier literature, in which the clastogenic effect of plasma from irradiated patients was well known. The effect was known to persist for several years and to cause transgenerational effects, making it similar to what we now call genomic instability. The review then examines the current data and controversies which are now beginning to resolve the questions concerning the mechanisms underlying the induction and transmission of both bystander effects and genomic instability. Finally, the possible impact of data concerning radiation-induced bystander effects on radiotherapy and radiation protection is discussed.

Animals↗
PubMed2001

Effect of low doses of ionizing radiation on cells cultured from the hematopoietic tissue of the Dublin Bay prawn, Nephrops norvegicus.

Explant cultures from the hematopoietic tissue of the Dublin Bay prawn, Nephrops norvegicus, were exposed to low doses of (60)Co gamma radiation. Cells growing from the explants were examined 7 days after irradiation using light and transmission electron microscopy and were also tested for their ability to produce signals indicative of a bystander effect. The exposed cultures displayed pronounced damage and were orders of magnitude more sensitive than the data in the literature would suggest for arthropod cells. The cultures were also more sensitive than mammalian cells that were exposed to similar doses. Cellular abnormalities included damage to cytoplasmic organelles, particularly the cytoskeleton. Abnormal mitochondria were also prominent. At low doses (0.5 Gy), nuclear damage was not apparent in the cultures, but there was evidence of a dose-dependent increase in apoptosis. The irradiated cultures released a factor into the medium that was capable of inducing apoptosis and cell death in unirradiated fish and human cells. This bystander effect was of a similar magnitude to that reported for mammalian cell systems. It is suggested that these crustaceans may be highly sensitive to radiation, unlike terrestrial arthropods and certain other invertebrates, which are generally considered to be radioresistant.

Animals↗
PubMed1998

Peripheral blood CD34+ cell count reliably predicts autograft yield.

A reliable measure to predict peripheral blood progenitor cell (PBPC) autograft CD34+ cell content is required to optimize the timing of PBPC collection. We prospectively examined the peripheral blood (PB) CD34+ cell count in 59 consecutive patients with various malignancies and analyzed the correlation between the PB CD34+ cell count and various parameters in the PBPC autograft. Two hundred and thirty-five collections were performed with a median of 4.0 collections per patient (range, 2-10). The median PB CD34+ cell count at the time of collection was 39 x 10(6)/1 (range, 0.0-285.6). The PBPC autograft parameters measured were the CD34+ cell, colony-forming unit granulocyte-macrophage (CFU-GM) and mononuclear cell (MNC) content. There was a strong linear correlation between PB CD34+ cells/l and autograft CD34+ cells/kg (r = 0.8477). The correlation with CFU-GM/kg (r = 0.5512) was weaker. There was no correlation between autograft CD34+ cells/kg and PB WBC (r= 0.0684), PB MNC (r = 0.1518) or PB platelet count (r = 0.2010). At our institution we aim to obtain a minimum of 0.5 x 10(6) CD34+ cells/kg with each day of collection. We demonstrate that such a collection can be reliably obtained if the PB CD34+ cell count exceeds 5.0 x 10(6)/l.

Blood Cell Count↗
PubMed1997

Radiation-induced carcinogenesis: studies using human epithelial cell lines.

It has proved difficult to develop suitable models to study radiation-induced carcinogenesis by using human epithelial cells. However, immortalised human epithelial cell lines have proved useful. Unirradiated cells from the human keratinocyte cell line (HPV-G) and the human embryonic lung cell line (L132) were found to be tumourigenic in T-cell-deficient mice; thus, they are not suitable for transformation studies. Human urothelial cell lines (SV-HUC-1, NT11, BC16) and the human thyroid epithelial cell line (HTori-3) were nontumourigenic. The urothelial cell lines were refractory to radiation-induced carcinogenesis, and only one small tumour was observed in 57 mice that received irradiated cells. Whereas tumours were not produced following irradiation of these urothelial cells, changes in anchorage-independent growth were observed after a single dose of 8 Gy gamma-irradiation but not after 2 or 4 Gy. Irradiation of the human thyroid epithelial cell line (HTori-3) in vitro resulted in tumour formation. Passaging of the cells in vitro before injection did not seem to be critical. Some of the cell lines derived from the primary thyroid tumours exhibited p53 mutations in exons 5, 6, 7, and 8, as detected by single-stranded conformational polymorphism (SSCP) analysis. Thus, the human thyroid epithelial cell line (HTori-3) looks promising as a model for investigating the molecular events in radiation-induced carcinogenesis.

Animals↗
PubMed1997

Survival of human epithelial cells irradiated with cobalt 60 as microcolonies or single cells.

Microcolonies of one to >50 cells were irradiated. They were assayed for survival using the Puck and Marcus clonogenic technique and the distant progeny were tested for expression of lethal mutations. The results show that epithelial cell colonies appear to respond as a unit rather than as individual cells to a radiation dose and the uncorrected initial surviving fraction is relatively constant irrespective of the number of cells present at the time the microcolony was irradiated. Irradiation of colonies or monolayers, which were then dispersed, confirmed this and showed slight sparing of the cells irradiated in contact compared with single cells but no sparing effect when the gap junctions were closed. Measurement of apoptosis 2 h post-irradiation showed higher levels in clones derived from cells irradiated in contact but delayed apoptosis in the progeny and lethal mutations appear to be associated with irradiation of single cells. Lethal mutations occurred in the progeny of cells irradiated as single cells for at least 30 cell generations but if cell microcolonies were irradiated the progeny survival showed a complex relationship with progenitor dose. When gap junction intercellular communication (GJIC) was blocked during and immediately post-irradiation using nitrosamines or TPA, cultures regained the initial survival and lethal mutation frequency seen with single cells. It is concluded that the presence of more than one cell in a microcolony at the time of irradiation does result in an altered and possibly a co-ordinated pattern of survival and lethal mutation expression but that inhibition of GJIC can reverse the effects of contact. The results may have implications for investigations of normal tissue response.

Apoptosis↗
PubMed1997

Induction of multiple PCR-SSCPE mobility shifts in p53 exons in cultures of normal human urothelium exposed to low-dose gamma-radiation.

We have previously shown that primary explant cultures of human urothelium exposed to low doses of gamma-radiation subsequently accumulate a high level of stable p53 but it was not clear from those studies whether this protein stabilization occurred through an event in another gene involved in p53 protein control or possibly an epigenetic event. In these experiments, primary urothelial cultures from five different patients were exposed to either 0.5 or 5 Gy gamma-radiation from a 60 Cobalt source and allowed to grow for 7-10 division cycles to allow development of any radiation-induced, non-lethal changes in the cells. C-myc, Bcl-2 and stable p53 proteins were found to be elevated in cultures following both radiation doses. PCR-SSCPE analysis of the p53 gene was performed on cultures in order to determine whether genetic mutations could be the underlying basis for persistent increased stable p53 expression. Following 0.5 Gy exposure, the cultures also developed multiple distinct 'foci' of rapidly dividing cells which strongly overexpressed p53. These grew on a background of morphologically normal cells. When such foci were selectively analysed for their p53 mutation status by PCR-SSCPE, there was evidence that they contained cells which had developed changes to the p53 gene post-irradiation. These changes appeared to occur more frequently in focal cells than in cells of normal morphological appearance in the same culture. These results may have mechanistic importance given the controversy regarding low-dose radiation effects and p53-related genomic instability.

Culture Techniques↗
PubMed1997

Lethal mutations and genomic instability.

The delayed expression of cell death in progeny of irradiated survivors was christened 'lethal mutations' by Tikvah Alper in 1984. The effect occurs when clones, or populations of cells grown up from irradiated progenitor cells, are replated and reassessed for cloning efficiency or population doubling time. The effect has been shown to be associated with the low dose shoulder region of the survival curve and is due to events occurring in the first two hours post irradiation, i.e. the 'fast repair' period. In this review the lethal mutation data accumulated over the past ten years is discussed in relation to our modern understanding of cellular and molecular events in radiation carcinogenesis and genomic instability research. It is suggested that lethal mutations are associated with a general epigenetic or field effect occurring in all irradiated cells, which makes them more prone to mutations, some of which are lethal. The implications of this for our current approach to risk estimates and therapeutic dose calculation, need to be addressed.

Animals↗
PubMed1997

Medium from irradiated human epithelial cells but not human fibroblasts reduces the clonogenic survival of unirradiated cells.

The results reported in this paper show a highly significant fall in cloning efficiency in unirradiated normal and malignant epithelial cell lines receiving medium from irradiated cultures. Medium irradiated in the absence of cells had no effect nor did irradiated medium from a fibroblast line, but irradiated medium from epithelial cells had an extremely toxic effect on unirradiated fibroblasts. Cells from four different cell lines were seeded, using standard techniques, 6 h prior to irradiation with cobalt 60 (Co60). At various times ranging from 1-60 h after irradiation, medium was removed, passed through a 0.22 mu filter and then used to replace the medium from parallel cultures seeded at cloning densities which had not been irradiated. The effect produced by the epithelial cell cultures was dependent on the cell number present at the time of irradiation, suggesting that a cell-derived factor is involved. The effect could be observed using medium taken from irradiated cultures as soon as 30 min/post irradiation. Examination of unirradiated cultures 48 h after receiving irradiated medium revealed the presence of high numbers of apoptotic bodies and other morphological evidence suggesting apoptosis may be a prominent mechanism of cell death responsible for the reduced cloning efficiency.

Cell Line↗
PubMed1997

p53 protein expression and increased SSCP mobility shifts in the p53 gene in normal urothelium cultured from smokers.

This study provides evidence of a significantly (P = 0.018) increased level of expression of the stable conformation of p53 in normal urothelial cells, cultured in vitro from bladder biopsies obtained from normal smokers without malignant disease of any site. With two significant exceptions, non-smokers showed low or no expression of this protein. Past smokers appeared to segregate into high or low p53 expressers, but the expression was not correlated with years since quitting smoking or with pack years smoked. The mean data in this group were not quite significantly different (P = 0.08) from the non-smoker group, due to the wide inter-patient variation. For most of the smoker group, pack years correlated with p53 expression with a mean unit of 1.7 +/- 0.37% p53 per pack year but there was a small group of very heavy smokers who showed lower than expected expression (approximately 0.3-0.8% p53 per pack year). These were statistical outliers (Grubbs test). No explanation could be found for this. Over-expression of p53 protein, often correlates with mutations in the gene, but may also indicate that breakdown of wild-type p53 has slowed. SSCP analysis of the biopsy material was not possible on all patients due to ethical constraints on the amounts of tissue which could be taken but in the cases where it was possible the association between loss of p53 protein function and mobility shifts in p53 exons 5-8 was confirmed with smokers having 3.5 times the number of mobility shifts detected in non-smoker DNA. Thus the results may point to a role for the early abrogation of p53 protein function in bladder carcinogenesis induced by cigarette smoking.

Adult↗