Search PubMed⌕ Search

Biomedical subjects

D M Hall

Publications and source records attributed to D M Hall.

At least 19 recordsLinked to original sources
PubMed2001

GalNAc glycoprotein expression by breast cell lines, primary breast cancer and normal breast epithelial membrane.

Over-expression of N-acetylgalactosamine glycoproteins as detected by binding of the lectin from Helix pomatia (HPA), is associated with metastatic competence and poor patient prognosis in a range of human adenocarcinomas. These glycoproteins remain poorly characterised, and their functional role has yet to be elucidated. This study describes characterisation of a range of human breast/breast cancer cell lines for the expression of the N-acetylgalactosaminylated glycoproteins of interest, and their comparison with normal breast epithelium and a range of clinical breast carcinoma samples. Confocal and light microscopy studies revealed cytochemical HPA-binding patterns consistent with a fundamental disruption in normal glycobiosynthetic pathways attending increasing metastatic potential. We report the most complete comparative analysis of HPA-binding ligands from cultured breast cells, clinical breast carcinoma samples and normal breast epithelium to date. Lectin blotting identified 11 major HPA-binding glycoprotein bands common to both clinical tumour samples and breast cell lines and 6 of these bands were also expressed by samples of normal breast epithelium, albeit at much lower levels. Moreover, very marked quantitative but not qualitative differences in levels of expression consistent with metastatic capability were noted.

Acetylgalactosamine↗
PubMed2001

The relationships between neonatal encephalopathy and cerebral palsy: a cohort study.

There is a high risk of cerebral palsy (CP) following neonatal encephalopathy (NE) with fits, often attributed to intrapartum asphyxia. The evidence for the association is inconclusive and antepartum factors offer an alternative explanation. A cohort study was carried out to assess the evidence for and against hypoxic ischaemic injury as the cause of NE-associated CP in term infants. A total of 57 159 consecutive births were enrolled. There were 150 cases with NE, of whom 92 had at least one fit and 58 had no fits. The incidence of all NE was 2.62 per 1000 births and of NE with fits was 1.61 per 1000 births. Infants with NE were followed-up to identify those with cerebral palsy. There were 13 cases of four-limb cerebral palsy and three with hemiplegia among the survivors. In 12 of the 13 cases of four-limb CP, a combination of low Apgar scores, an early onset acute evolving encephalopathy, acidosis, renal dysfunction and the absence of antepartum factors suggested an acute intrapartum event as the immediate cause of the NE. An obstetric event likely to cause acute hypoxic injury was identified in four of the 12 cases. The clinical picture was similar in the four with and the eight without a specific obstetric event. The pathway leading to NE-associated CP remains unexplained, but intrapartum events appear to play a major role in most cases.

Journal Article↗
PubMed2001

Aging lowers steady-state antioxidant enzyme and stress protein expression in primary hepatocytes.

It has been reported that the isolation and culture of primary hepatocytes can compromise cellular ability to constituitively express antioxidant enzyme (AE) genes, making it difficult to study their regulation ex vivo. In the present study, the steady-state expression of manganese-containing superoxide dismutase, copper- and zinc-containing superoxide dismutase, catalase, and glutathione peroxidase was assessed in primary hepatocytes isolated from young and senescent rats and cultured in MATRIGEL: There was no change in steady-state superoxide dismutase protein or activity levels in cells collected from young animals and cultured for 7 days. Catalase expression was initially increased, and then it declined 30%. In contrast, superoxide dismutase expression declined 60% and catalase expression declined 50% in cells from senescent animals. Constitutive and inducible 70-kDa heat shock protein expression increased coincident with declining AE levels in the young cells but not senescent cells. For both age groups, electron micrographs showed rounded hepatocytes with abundant rough endoplasmic reticulum, mitochondria, and peroxisomes. Hepatocytes were organized into clusters of 6-12 cells surrounding a large central lumen devoid of microvilli. Each cluster also contained smaller microvilli-lined lumens between adjacent hepatocytes that resembled canniculi. The plasma membranes of these lumens were sealed from the extracellular space by junctional complexes. Gap junctions in the plasma membrane suggest that hepatocytes were capable of intercellular communication. We conclude that the Matrigel system can be used to study AE regulation in primary hepatocytes from young and senescent animals, provided that experiments can be conducted within a time frame of 5-7 days in culture. These data also support the hypothesis that aging compromises hepatocellular ability to maintain AE status and upregulate stress protein expression.

Aging↗
PubMed2001

Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia.

This work tested the hypotheses that splanchnic oxidant generation is important in determining heat tolerance and that inappropriate.NO production may be involved in circulatory dysfunction with heat stroke. We monitored colonic temperature (T(c)), heart rate, mean arterial pressure, and splanchnic blood flow (SBF) in anesthetized rats exposed to 40 degrees C ambient temperature. Heating rate, heating time, and thermal load determined heat tolerance. Portal blood was regularly collected for determination of radical and endotoxin content. Elevating T(c) from 37 to 41.5 degrees C reduced SBF by 40% and stimulated production of the radicals ceruloplasmin, semiquinone, and penta-coordinate iron(II) nitrosyl-heme (heme-.NO). Portal endotoxin concentration rose from 28 to 59 pg/ml (P < 0.05). Compared with heat stress alone, heat plus treatment with the nitric oxide synthase (NOS) antagonist N(omega)-nitro-L-arginine methyl ester (L-NAME) dose dependently depressed heme-.NO production and increased ceruloplasmin and semiquinone levels. L-NAME also significantly reduced lowered SBF, increased portal endotoxin concentration, and reduced heat tolerance (P < 0.05). The NOS II and diamine oxidase antagonist aminoguanidine, the superoxide anion scavenger superoxide dismutase, and the xanthine oxidase antagonist allopurinol slowed the rates of heme-.NO production, decreased ceruloplasmin and semiquinone levels, and preserved SBF. However, only aminoguanidine and allopurinol improved heat tolerance, and only allpourinol eliminated the rise in portal endotoxin content. We conclude that hyperthermia stimulates xanthine oxidase production of reactive oxygen species that activate metals and limit heat tolerance by promoting circulatory and intestinal barrier dysfunction. In addition, intact NOS activity is required for normal stress tolerance, whereas overproduction of.NO may contribute to the nonprogrammed splanchnic dilation that precedes vascular collapse with heat stroke.

Allopurinol↗
PubMed2000

Ovariectomy does not induce osteopenia through interleukin-6 in rhesus monkeys (Macaca mulatta).

To characterize the role of interleukin-6 (IL-6) in estrogen (E2)-depletion bone loss, we utilized a nonhuman primate model of human skeletal physiology. Adult female rhesus monkeys were sham-operated (S; n = 5), ovariectomized (ovx; n = 10), or ovx followed by E2 replacement (ovx + E2; n = 10) and evaluated for the indicated parameters at 0, 3, 6, and 9 months post-ovx. Lumbar spine bone mineral density (BMD) decreased by 3 months and continued to decline through 9 months in the ovx, but not in the ovx + E2 or S groups. Middle and distal radius BMD was decreased at 9 months in the ovx, but not in the ovx + E2 or S groups. The S group had marked fluctuations in bone remodeling parameters, and cytokine levels in S animals were consistent with menstrual cycling, and therefore only those values in the ovx and ovx + E2 groups are reported. Serum osteocalcin and skeletal-specific alkaline phosphatase were elevated in the ovx group compared with the ovx + E2 group. There was no difference in serum or bone marrow plasma IL-6 levels between the ovx and ovx + E2 groups. Similarly, there was no difference in basal or phorbol ester-stimulated IL-6 levels of peripheral blood mononuclear cell or bone marrow cell culture supernatants between groups. There was no difference in serum or bone marrow soluble IL-6 receptor between groups. However, the bone marrow plasma soluble IL-6 receptor levels were transiently increased from baseline at 3 months in the ovx but not in the ovx + E2 group. In summary, there was no bone loss in the ovx + E2 group, although the serum and bone marrow IL-6 levels were similar to those of the ovx group. These data suggest that modulation of IL-6 is not the key mechanism through which estrogen deprivation mediates bone loss in rhesus monkeys.

Animals↗
PubMed2000

Levels of satisfaction of 'low-risk' mothers with their current health visiting service.

AIMS AND OBJECTIVES: To assess the expressed levels of satisfaction of 'low-risk' mothers with the current health visiting service. Setting Sheffield, England, Autumn 1997. METHODOLOGY: Self-completion, postal questionnaire (initial postcard reminder followed by a second letter and questionnaire) to a sample of 403 mothers assessed as 'low priority' by their health visitor. Questions largely related to maternal opinion of the adequacy of the health visiting service delivered during the first 9-12 months. The local research ethics committee approved the study. RESULTS: A corrected response rate of 75% with little evidence of significant bias. A high proportion (86%) of women stated that they were either 'fairly' or 'very' satisfied with the service they had received from their health visitor with regard to their baby. A lower proportion (72%) was equally satisfied with the service they had received in respect of their own health. Despite an average number of approximately 10 contacts in relation to infant health with the health visitor during the first year of life, some 6% of women wanted more frequent contacts, particularly in the first few weeks. Study limitations The questionnaire was designed specifically for the study and validation was limited. The study population comprised a selected, 'low-risk' group. CONCLUSIONS: The number of reported contacts with the health visitor seemed to greatly exceed those indicated by a basic child health surveillance programme. The overall level of maternal satisfaction is high, though a minority of women would like more support. Dissatisfaction was expressed with the lack of an appointment system for clinics, poor punctuality in home visits, and inappropriate or inadequate advice.

Adolescent↗
PubMed2000

School nursing: costs and potential benefits.

BACKGROUND: Previous reports that variations in school nursing resources across the UK had no relationship to deprivation; controversy about the changing role of the school nursing service. OBJECTIVES: To measure the resources allocated to school nursing, determine whether the variations can be explained by deprivation, and assess whether the allocation of school nursing time to a range of tasks is in line with current evidence and perceptions of changing needs. STUDY DESIGN: Quantitative economic analysis; qualitative descriptive study. SETTING: Detailed study of four English districts with diverse characteristics; staffing and service questionnaire and telephone survey of 62 districts. MAIN MEASURES: Staff resources and their salaries; measures of population and deprivation; activity statistics. RESULTS: There were wide variations in the cost of the school nursing service, but in contrast to previous reports 24% of the variance was explained by deprivation. There were no clear associations with any other social or educational variables. The greatest allocation of time was in routine screening and surveillance tasks. Relatively little time was allocated to other activities such as health promotion, support of special needs or unwell children, or teenage clinics. The expenditure on school nursing is only loosely related to deprivation and the results of this study offer guidance on what districts should spend to achieve equity of provision. CONCLUSIONS: The current allocation of resources to school nursing in between districts comparisons is not equitable and the use of school nursing time is out of step with current evidence of need and effectiveness.

Adolescent↗
PubMed2000

Hitting the target: the equitable distribution of health visitors across caseloads.

BACKGROUND: Health visitors in the United Kingdom work mainly with pre-school children and their mothers. Their distribution across the population is largely historical, highly variable and relates poorly to indicators of population need. METHODS: A range of largely routine data sources were used to describe the nature, variation and statistical determinants of the workload of individual health visitors in Sheffield, England, in 1996-1997. Regression models were tested relating measures of need and deprivation to the total number of client contacts. RESULTS: Caseloads were smaller in the most deprived areas, with wide variation. Most (93 per cent) contacts were with mothers and young children. Health visitors visited the clients designated as highest priority on average 4.7 times more often than routine clients. The main reasons for high priority ratings were child protection concerns, maternal mental health problems, child development and health concerns, and first-time mothers in the postnatal period. Half of all client contacts were with low-priority families for routine child health surveillance or were client initiated. Models based on the number of children under five and any one of a range of measures of social deprivation account for 57-59 per cent of variation in workload and could be used to allocate resources more equitably. CONCLUSIONS: Although most health visitors apparently subscribe to the principle of targeting, the extent varies widely. Constraints on targeting are routine child health surveillance reviews, and client demands. More equitable allocation of health visitors and more explicit targeting policies might increase the effectiveness of the health visiting service.

Child↗
PubMed2000

Caloric restriction improves thermotolerance and reduces hyperthermia-induced cellular damage in old rats.

Adult-onset, long-term caloric restriction (CR) prolongs maximum life span in laboratory rodents. However, the effect of this intervention on an organism's ability to cope with a physical challenge has not been explored. We investigated the influence of CR and aging on stress tolerance in old rats exposed to an environmental heating protocol on two consecutive days. We hypothesized that CR would increase heat tolerance by reducing cellular stress and subsequent accrual of oxidative injury. All calorically restricted rats survived both heat exposures compared with only 50% of their control-fed counterparts. CR also decreased heat-induced radical generation, stress protein accumulation, and cellular injury in the liver. In addition, heat stress stimulated marked induction of the antioxidant enzymes manganese-containing superoxide dismutase and catalase, along with strong nuclear catalase expression in liver samples from rats subjected to CR. In contrast, stress-related induction of antioxidant enzymes was blunted, and nuclear catalase expression was unchanged from euthermic conditions in the control-fed group. These data suggest that CR reduces cellular injury and improves heat tolerance of old animals by lowering radical production and preserving cellular ability to adapt to stress through antioxidant enzyme induction and translocation of these proteins to the nucleus.

Adaptation, Physiological↗
PubMed2000

Aging reduces adaptive capacity and stress protein expression in the liver after heat stress.

A decline in an organism's ability to cope with stress through acute response protein expression may contribute to stress intolerance with aging. We investigated the influence of aging on stress tolerance and the capacity to synthesize the 70-kDa heat shock protein (HSP70) in young and old rats exposed to an environmental heating protocol. Livers were assessed for injury and HSP70 expression after heat stress by use of immunohistochemical and immunoblotting techniques. The inducible HSP70 response in the cytoplasm and nucleus was markedly reduced with age at several time points over a 48-h recovery period, although senescent rats were able to strongly express HSP70 early in recovery. Older animals had extensive zone-specific liver injury, which corresponded to the diminished HSP70 response observed in these regions, and a significant reduction in thermotolerance compared with their young counterparts. These data highlight the regional nature of stress-induced injury and HSP70 expression in the liver and the impact of aging on these responses. Furthermore, the results suggest a functional link between the age-related decrements in the expression of inducible HSP70 and the pathophysiological responses to heat stress.

Adaptation, Physiological↗
PubMed1999

Assessment of stool colour in community management of prolonged jaundice in infancy.

Jaundice persisting beyond the first 2 wk of life is often regarded as an indication for investigation to exclude cholestatic liver disease. Most babies with prolonged jaundice have breast milk-related jaundice, which is a benign condition. Cholestatic liver disease is usually accompanied by pale stools and yellow or orange urine. A community programme was established to ascertain the incidence of prolonged jaundice and determine whether abnormal stool and urine colour could be used to assist primary care staff in referral decisions. Data were collected on normal stool and urine colour and used to devise a colour chart and information sheet for parents. Babies with prolonged jaundice were identified and referred for investigation. In all, 3661 babies were recruited into the study, of which 127 were jaundiced at 28 d of age. Of these, 125 were breastfed. The incidence of jaundice in breastfed babies at 28 d was 9.2% (95% CI 7.8%-11.0%) Abnormal liver function tests (LFTs) were common, but no baby had abnormal stool or urine colour and none was found to have liver disease. Jaundiced breastfed babies who are well are unlikely to have serious disease. Elevated LFTs are compatible with a diagnosis of breast milk-related jaundice. Prolonged jaundice in bottle-fed babies, and persistent pallor of stools or yellow/orange urine, are rare and merit immediate referral. Parents and professionals can be advised to report pale stools without generating a large number of unnecessary referrals. Further work is needed to determine whether a colour chart reduces the mean age of referral and treatment of infants with cholestatic liver disease.

Analysis of Variance↗
PubMed1999

The infant index: a new outcome measure for pre-school children's services.

BACKGROUND: The evaluation of community services for preschool children is hampered by the lack of valid and routinely available outcome measures. This study examines the use of data collected by teachers in response to educational legislation to determine whether a routine measure of attainments in primary school is sensitive to factors known to affect mental development. METHOD: A community child health dataset for the cohort of children born in Sheffield in 1990-1991 was matched with a dataset provided by schools in 1995-1996. The educational data consisted of the Infant Index scores which measure education attainments in reception class pupils. RESULTS: We matched 4487 children from both datasets, which represented 75 per cent of all children born in the 1990-1991 cohort. Factors which predicted a poor Infant Index included male gender (odds ratio (OR) = 2.1, 95 per cent confidence interval (CI)= 1.8-2.6), low birthweight (OR = 1.4, 95 per cent CI = 1.1-1.9) and lack of breast feeding either by intention to feed (OR = 1.3, 95 per cent CI = 1.1-1.7) or actual feeding practice at one month (OR = 1.5, 95 per cent CI = 1.1-2.0). Other factors associated with a poor outcome for the child were postnatal depression, number of pregnancies, ethnicity, pre-school educational experiences and poor housing. CONCLUSIONS: Although the results are interesting in themselves, the main significance of our project is in establishing a link between routinely collected health data and routine education data. This could facilitate research in the future thus leading to a considerable saving in the cost of long-term intervention studies.

Birth Weight↗