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S Moffatt

Publications and source records attributed to S Moffatt.

At least 19 recordsLinked to original sources
PubMed2001

'Even the birds round here cough': stigma, air pollution and health in Teesside.

In this paper we explore how the presence of hazardous industry may affect the identity of a place and the people who live there. Drawing on Goffman's seminal work on stigma - together with recent debates on environmental and technological stigma - we extend the concepts of difference and spoiled identity from the individual to place. The paper is based on a qualitative study which explored public perceptions of the risks to health from air pollution in Teesside, a heavily industrialised area in north-east England. We did not set out to study stigma per se in this study, but emergent themes produced by grounded theory analysis highlighted the way in which the presence of technologies, air pollution, poor health and social exclusion may be used as 'discrediting' characteristics, to stigmatise one place, whilst confirming the usualness of another. We demonstrate place stigma as a complex, multiple and re-inforcing concept.

Adolescent↗
PubMed2001

Cell adhesion molecules in human osteoblasts: structure and function.

Osteoblasts and bone lining cells form a near continuous layer covering the bone surface and interactions between these cells and the organic matrix of bone are important determinants of osteoblast proliferation and differentiation. In addition, cells of the osteoblast-lineage form functional communications with each other, with the extra-cellular matrix and with osteocytes through cytoplasmic processes extending through canaliculi in the bone. Together, these cells form a network of putative importance in the regulation of skeletal homeostasis. Cell-cell and cell-matrix interactions are mediated by members of several families of cell adhesion molecules, and knowledge of their interactions will be of fundamental importance in understanding the role of osteoblast in skeletal turnover. Here, the expression pattern of members of the major families of cell adhesion molecules by cells of the osteoblast lineage is reviewed. Special emphasis has been placed on human tissues. In addition, the possibility that cells at progressive stages of the osteoblast lineage have different profiles of cell adhesion molecule expression is explored, and the putative significance of cell-matrix interactions in human skeletal disease briefly discussed.

Cadherins↗
PubMed2000

Immunization with DNA, adenovirus or both in biodegradable alginate microspheres: effect of route of inoculation on immune response.

To determine the potential for biodegradable alginate microspheres to be used as a delivery vehicle for DNA based vaccines, we constructed a plasmid, pMNe-gal-SV40, containing the bacterial beta-galactosidase (LacZ) gene under the control of the murine cytomegalovirus (MCMV) immediate-early promoter and the simian virus 40 (SV40) polyadenylation signal. The effect of the route of administration and co-administration of adenovirus on systemic and mucosal immune responses were investigated. Mice were inoculated orally, intranasally (i.n.), intramuscularly (i.m.), subcutaneously (s.c.) or intraperitoneally (i.p.) on days 0, 14 and 28 with microspheres containing plasmid DNA, bovine adenovirus type 3 (BAd3) or plasmid DNA + BAd3. Systemic routes of immunization (i.m., s.c. and i.p.) resulted in higher LacZ- or BAd3-specific IgG ELISA titers compared to those obtained by mucosal routes of inoculation (oral and i.n.). Mucosal immunization led to slightly higher titers of LacZ- or BAd3-specific IgA at mucosal sites compared to those obtained by the various systemic routes. All the routes of immunization induced LacZ-specific lymphoproliferation. Co-administration of BAd3 enhanced the LacZ-specific IgG response irrespective of the route of administration.

3T3 Cells↗
PubMed2000

Circumvention of vector-specific neutralizing antibody response by alternating use of human and non-human adenoviruses: implications in gene therapy.

To determine whether non-human adenovirus-specific antibodies are cross-neutralizing, rabbit and mouse anti-human adenovirus type 5 (HAd5), anti-bovine adenovirus type 3 (BAd3), and anti-porcine adenovirus type 3 (PAd3) sera were used in cross-virus neutralization assays. Adenovirus neutralizing antibodies were found to be virus-specific, suggesting that virus neutralizing epitope differs significantly in HAd5, BAd3, and PAd3. To further investigate whether immunity to an HAd5-derived vector could be circumvented by the use of non-human adenoviruses in vivo, mice were first immunized either intranasally or intraperitoneally with HAd5, BAd3, PAd3, or BAd3 + PAd3, and after development of adenovirus-specific antibodies, animals were inoculated with the HAd5 recombinant (AdCA36lacZ) containing the bacterial beta-galactosidase gene under the control of murine cytomegalovirus immediate-early promoter. Virus-inoculated animals developed virus-specific IgG and IgA antibodies. LacZ expression in animals initially primed with HAd5 was significantly reduced (P < 0.05), suggesting that the immune response against the vector could prevent the transgene expression following subsequent inoculation of the same vector, whereas LacZ expression in mice initially primed with BAd3, PAd3, or BAd3 + PAd3 was significantly higher (P > 0.05) than that obtained in HAd5-primed animals. Our results suggest that HAd5-, BAd3-, or PAd3-based vectors may be used sequentially for human gene therapy or vaccine production as a means to avoid immunity to the vector.

Adenoviruses, Human↗
PubMed2000

"Impact? What impact?" Epidemiological research findings in the public domain: a case study from north-east England.

This paper reflects on the dissemination of potentially controversial research evidence about industrial air pollution and health in north-east England. It draws on a participant observation study of the local impact of a four-year epidemiological research programme in Teesside. The difficulties in and obstacles to disseminating research findings are explored. It may thus be described as a study of the impact of a study. We look at institutional resistance (including from the funders of the research) to any evidence indicating adverse health effects from industrial pollution. We also look at the failure of researchers to surmount such resistance and to communicate effectively with those who lived in the vicinity of the major industrial operations. This leads us to consider how conflicting notions of accountability coloured dissemination strategies as well as researchers' judgements. We offer a critique of fashionable and unduly consensual notions of a 'user community', in a context where different 'user communities' had incompatible expectations about the purpose of a piece of research and the significance of the data to emerge from it. The study also highlights the difficulties of disseminating research findings when the topic has the potential to affect economic interests.

Air Pollution↗
PubMed2000

An exploration of awareness bias in two environmental epidemiology studies.

Awareness bias in environmental health research is the tendency to report more illness because of concerns arising from proximity to a hazard in the absence of a measurable biological effect. Such bias complicates the interpretation of self-reported symptoms in communities exposed to emissions from heavy industry. We used data from two epidemiologic studies in Northeast England where community concerns existed about health risks from industry. An association between proximity to industry and self-reported respiratory and nonrespiratory illnesses and symptoms had been found in one study but not in the other. An indicator of concern about industrial pollution was constructed from responses to a 17-item questionnaire about issues that had caused stress or anxiety. Univariate and multivariate analyses of health outcome variables in both studies showed that individuals with "industry-related worries" reported more illness, irrespective of proximity to industry. We conclude that self-reported illness was influenced by both worry and proximity to industry, but that worry about the hazard had the greatest effect on self-reported illness. We suggest that because absolute certainty about the role and extent of awareness bias in environmental epidemiology studies is unlikely to be achieved, self-reported data should be supplemented with other observations.

Adult↗
PubMed2000

Is it feasible to construct a community profile of exposure to industrial air pollution?

OBJECTIVE: An epidemiological investigation to assess the validity of residential proximity to industry as a measure of community exposure. METHODS: 19 Housing estates in Teesside (population 1991: 77 330) in north east England were grouped into zones: A=near; B=intermediate; C=further from industry. With residential proximity of socioeconomically matched populations as a starting point a historical land use survey, historical air quality reports, air quality monitoring, dispersion modelling data, and questionnaire data, were examined. RESULTS: The populations in zones A, B, and C were similar for socioeconomic indicators and smoking history. Areas currently closest to industry had also been closest for most of the 20th century. Historical reports highlighted the influence of industrial emissions to local air quality, but it was difficult to follow spatial pollution patterns over time. Whereas contemporary NO(x) and benzene concentrations showed no geographical variation, dispersion modelling of emissions (116 industrial stacks, traffic, and domestic sources) showed a gradient associated with industry. The presumed exposure gradient of areas by proximity to industry (A>B>C) was evident for all of zone A and most of zones B and C. CONCLUSIONS: It was feasible to assemble a picture of community exposure by integration of measurements from different sources. Proximity of residence was a reasonable surrogate for complex community exposure.

Air Pollutants↗
PubMed1999

Residential proximity to industry and adverse birth outcomes.

We studied birth statistics in women living at varying proximity to major steel and petrochemical industries in Teesside, UK. We found no evidence to support the hypothesis that living close to these major industries led to adverse birth outcomes.

Air Pollutants↗
PubMed1999

Serologic study of human parvovirus B19 infection in pregnancy in Japan.

OBJECTIVES: To clarify the relationship between hydrops fetalis and parvovirus outbreaks in the community, seroprevalence of B19 antibody among women of childbearing age, and adverse effects of intrauterine B19 infection. METHODS: Sera were collected from 168 cases of hydrops fetalis which were diagnosed between 1987 and 1997 in Miyagi prefecture, Japan, from 232 healthy pregnant women in 1987 and 277 healthy pregnant women in 1997 in Miyagi, and from 48 women infected with B19 during pregnancy. The sera were examined for B19 IgG and IgM antibodies by enzyme-linked immunosorbent assay and for B19 DNA by polymerase chain reaction. The number of cases of erythema infectiosum in Miyagi had been monitored each month. RESULTS: Thirteen of the 168 cases of hydrops fetalis were found to be caused by intrauterine B19 infection and 12 of the 13 cases clustered in two periods of outbreaks of erythema infectiosum in the community. The positive rates of B19 IgG antibody between 1987 and 1997 were significantly different: 33% in 1987 and 46% in 1997. Nine of the 48 women infected during pregnancy showed adverse effects of the fetus: eight hydrops fetalis and one early abortion with positive B19 DNA. The fetal death rate (>12 weeks of gestation) among them was 15% (7/48), far higher than the calculated 1% among the general population. The nine mothers with adverse fetal outcomes had contact with the infectious source at the 16 weeks of gestation or earlier. CONCLUSIONS: These data clearly showed a relationship between hydrops fetalis and parvovirus outbreaks in the community, and it may be important to follow the seroprevalence for an extrapolated period time to predict occurrence of hydrops fetalis caused by B19. Also the data indicated that the gestational week infection occurred is the most important determinant of an adverse effect to the fetus as described previously.

Adolescent↗
PubMed1999

Parvovirus B19 infection induces apoptosis of erythroid cells in vitro and in vivo.

OBJECTIVE: intrauterine parvovirus B19 infection is related to non-immune hydrops fetalis, the pathogenesis of which is based on the strict tropism of B19 for erythroid precursor cells and the massive destruction of the infected erythroid cells, although the mechanism of beta19-induced cytotoxicity has not been studied in detail. The purpose of this study is to provide empirical evidence that beta19 induces apoptosis of erythroid cells both in vitro and ill vivo. METHODS: we analysed culture cells infected in vitro by B19 and tissues of nine cases of hydrops fetalis caused by B19 intrauterine infection by histological and biological methods. RESULTS: cells infected iil vitro by B19 showed nuclear changes characteristic of apoptosis by light microscopic examination and DNA extracted from the infected cells was fragmented. Electron microscopic examination showed the nuclei of infected cells contained crescent-shaped clumps of heterochromatin with increased density and double staining with anti-B1 9 antibody and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) confirmed apoptosis of individual cells. Tissues of cases of hydrops fetalis caused by B19 contained erythroid cells with nuclear inclusions and characteristic nuclear changes of apoptosis by light microscopy. The double-staining confirmed apoptosis of erythroid cells in the tissues. Immunohistochemical analysis with antibodies against cellular factors involved in apoptosis showed that caspase3, p53 and p21 were positive in infected cells.

Apoptosis↗
PubMed1998

The incidence of, and factors leading to, parvovirus B19-related hydrops fetalis following maternal infection; report of 10 cases and meta-analysis.

OBJECTIVES: to clarify the approximation of the frequency of B19-related nonimmune hydrops fetalis (NIHF), and to know the critical period during which maternal infection led to NIHF. METHODS: we investigated the characteristics of 10 cases of antenatal B19 infection diagnosed over the past 10 years in Miyagi prefecture, Japan, and performed a meta-analysis of these cases and those previously reported in the literature. RESULTS: NIHF caused by intrauterine B19 infection was diagnosed between 11 and 23 weeks of gestation in 10 women over the past 10 years in Miyagi prefecture, Japan. The source of infection was the mother's older child in six out of 10 cases, and children at a kindergarten where the mothers worked in two cases. The interval between the onset of infection and the diagnosis of NIHF ranged from 2 to 6 weeks. B19 infection was responsible for 10 (15.2%) in 66 cases of aetiology unknown NIHF in this study, and for 57 (19.1%) of 299 cases of non-malformed or aetiology-unknown NIHF by meta-analysis of the literature. Meta-analysis of the 165 reported cases of antenatal B19 infection, including the 10 cases described above, showed that there was a 10.2% excess risk of fetal death in women infected with B19 during pregnancy and a 12.40% excess risk in women infected during the first 20 weeks of pregnancy. Transplacental transmission was confirmed in 69 (24.1%) of 286 cases. The mean gestational age at diagnosis of NIHF was 22.8 +/- 5.1 weeks. The mean interval between the onset of maternal infection and diagnosis of NIHF was 6.2 +/- 3.7 weeks. CONCLUSIONS: these approximations will be useful for counselling and management for pregnant women. The critical period during which maternal infection led to NIHF correlated with the hepatic period of hematopoietic activity. These findings suggest that parvovirus B19 may have an affinity for erythroid lineage cells at the hepatic stage of hematopoiesis, which may strongly influence the clinical features of feto-maternal B19 infection.

Female↗
PubMed1998

Human parvovirus B19 nonstructural (NS1) protein induces apoptosis in erythroid lineage cells.

Infection of erythroid-lineage cells by human parvovirus B19 is characterized by a gradual cytocidal effect. Accumulating evidence now implicates the nonstructural (NS1) protein of the virus in cytotoxicity, but the mechanism underlying the NS1-induced cell death is not known. Using a stringent regulatory system, we demonstrate that NS1 cytotoxicity is closely related to apoptosis, as evidenced by cell morphology, genomic DNA fragmentation, and cell cycle analysis with the human erythroleukemia cell line K562 and the erythropoietin-dependent megakaryocytic cell line UT-7/Epo. Apoptosis was significantly inhibited by an interleukin-1beta (IL-1beta)-converting enzyme (ICE)/CED-3 family protease inhibitor, Ac-DEVD-CHO (CPP32; caspase 3), whereas a similar inhibitor of ICE (caspase 1), Ac-YVAD-CHO, had no effect. Furthermore, stable expression of the human Bcl-2 proto-oncogene resulted in near-total protection from cell death in response to NS1 induction. Mutations engineered into the nucleoside triphosphate-binding domain of NS1 significantly rescued cells from NS1-induced apoptosis without having any effect on NS1-induced activation of the IL-6 gene expression which is mediated by NF-kappaB. Furthermore, using pentoxifylline, an inhibitor of NF-kappaB activation, we demonstrate that the NF-kappaB-mediated IL-6 activation by NS1 is uncoupled from the apoptotic pathway. This functional dissection indicates a complexity underlying the biochemical function of human parvovirus NS1 in transcriptional activation and induction of apoptosis. Our findings indicate that NS1 of parvovirus B19 induces cell death by apoptosis in at least erythroid-lineage cells by a pathway that involves caspase 3, whose activation may be a key event during NS1-induced cell death.

Apoptosis↗
PubMed1998

Does living near a constellation of petrochemical, steel, and other industries impair health?

OBJECTIVES: To investigate concern that local industrial air pollution in Teesside, England, was causing poor health, several areas there were compared with parts of the City of Sunderland. METHODS: Populations in similar social and economic circumstances but varying in their proximity to major industries were compared. Study populations lived in 27 housing estates in Teesside and Sunderland, north east England, with some data from subsets of estates. The estates were aggregated into zones (designated as A, B, and C in Teesside where A is closest to and C furthest from industry, and S in Sunderland). Zone S provided a reference area. The hypothesis was that a health gradient both within Teesside (A > B > C) and between Teesside and Sunderland (ABC > S) would indicate a possible health effect of local industrial air pollution. Data presented were: mortality (1981-91) from 27 housing estates; population self completion questionnaire survey data (1993, 9115 subjects) from 15 housing estates; and general practitioner (GP) consultation data (1989-94) from 2201 subjects in 12 Teesside estates. RESULTS: The populations in the four zones were comparable for indicators including smoking habits, residential histories, and unemployment. All cause and cause specific mortalities were high compared with England and Wales. Mortality in all Teesside zones (ABC) combined was mostly higher than in zone S. In people aged 0-64, lung cancer and respiratory disease showed gradients with highest mortality in areas closest to industry (A > B > C and ABC > S). The association was clearest for lung cancer in women (0-64 years old, trend across zones ABC, p = 0.07, directly standardised rate ratio relative to zone S was 169 (95% confidence interval (95% CI) 116-122)). There were no important, consistent gradients in the hypothesised direction between zones in consultation rates in general practice, and self reported respiratory and nonrespiratory health including asthma. CONCLUSIONS: There was no clear evidence that living close to industry was associated with morbidity, including asthma, or for most measures of mortality. For lung cancer in women the gradients indicated a health effect of local industrial air pollution. In the age group 0-64 observed gradients in lung cancer in men and mortality from respiratory disease in men and women were consistent with the study hypothesis, although not significant. The reasons for the different patterns at different ages, and between men and women, remain a puzzle.

Adolescent↗
PubMed1998

Lung cancer, proximity to industry, and poverty in northeast England.

This study assesses whether deprived populations living close to industry experience greater mortality from lung cancer than populations with comparable socioeconomic characteristics living farther away. Mortality data, census data, a postal survey of living circumstances, historic and contemporary data on air quality and a historic land-use survey were used. Analysis was based on two conurbations in England, Teesside and Sunderland. Housing estates in Teesside were selected based on socioeconomic criteria and distinguished by proximity to steel and chemical industries; they were grouped into three zones: near (A), intermediate (B), and farther (C), with a single zone in Sunderland. We included 14,962 deaths in 27 estates. Standardized mortality ratios (SMR) for lung cancer [International Classification of Diseases #9 (ICD-9) 162] and cancers other than lung (ICD-9 140-239, excluding 162), and sex ratios were calculated. Mortality from lung cancer was well above national levels in all zones. For men, a weak gradient corresponding with proximity to industry at younger ages reversed at older ages. In women 0-64 years of age, stronger gradients in lung cancer mortality corresponded with proximity to industry across zones A, B, and C (SMR = 393, 251, 242, respectively). Overall rates in Teesside were higher than Sunderland rates for women aged 0-64 years (SMR = 287 vs. 185) and 65-74 years (SMR = 190 vs. 157). The association between raised lung cancer mortality and proximity to industry in women under 75 years of age could not be explained by smoking, occupation, socioeconomic factors, or artifact. Explanations for differences between men and women may include gender-specific occupational experiences and smoking patterns. Our judgment is that the observed gradient in women points to a role for industrial air pollution.

Adolescent↗
PubMed1997

Induction of IL-1 beta-converting enzyme-independent apoptosis by IL-2 in human T cell lines.

Our previous study demonstrated that IL-2 suppressed growth of human T cell lines, in which the suppression was observed with members among HTLV-I-infected T cell lines independent of IL-2 for growth. In this study, we examined the molecular mechanism of IL-2-induced growth suppression with two HTLV-I-infected T cell lines; TL-OmI expressing endogenously three subunits, i.e. alpha, beta and gamma chains, of the IL-2 receptor, and an MT-1 transfectant expressing the endogenous alpha and gamma chains and exogenous beta chain. Our analysis revealed that IL-2 induced apoptosis in both T cell lines. Experiments with inhibitors for the proteases responsible for apoptosis signals showed that caspase 1 (IL-1 beta-converting enzyme) was not involved in apoptosis induced by IL-2. Other MT-1 sublines introduced with mutant beta chains demonstrated that IL-2-induced apoptosis required signals from both the serine-rich (S) region and acidic (A) region of the IL-2 receptor beta chain, which are essential but not critical for IL-2-mediated cell growth respectively. Collectively, IL-2 functions not only on growth promotion and prevention of apoptosis but also on induction of apoptosis, which may be implicated in physiological regulation of immune reactions by controlling growth and activation of T cells.

Apoptosis↗
PubMed1996

A cytotoxic nonstructural protein, NS1, of human parvovirus B19 induces activation of interleukin-6 gene expression.

We examined the biological function of a nonstructural regulatory protein, NS1, of human parvovirus B19. Because of the cytotoxic activity of NS1, human hematopoietic cell lines, K562, Raji, and THP-1, were established as transfectants which produce the viral NS1 protein upon induction by using bacterial lactose repressor/operator system. NS1 was significantly produced in the three transfectant cells in an inducer dose- and time-dependent manner. Surprisingly, these three transfectants secreted an inflammatory cytokine, interleukin-6 (IL-6), in response to induction. However, no production of other related cytokines, IL-1beta, IL-8, or tumor necrosis factor alpha, was seen. Moreover, NS1-primed IL-6 induction was transiently demonstrated in primary human endothelial cells. Analysis with luciferase reporter plasmids carrying IL-6 promoter mutant fragments demonstrated that NS1 effect is mediated by a NF-kappaB binding site in the IL-6 promoter region, strongly implying that NS1 functions as a trans-acting transcriptional activator on the IL-6 promoter. Our novel finding, IL-6 induction by NS1, supports the possible relationship between parvovirus B19 infection and polyclonal activation of B cells in rheumatoid arthritis and indicates that NS1 protein may play a significant role in the pathogenesis of some B19-associated diseases by modulating the expression of host cellular genes.

Animals↗