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Biomedical subjects

P Smith

Publications and source records attributed to P Smith.

At least 145 records · Page 8Linked to original sources
PubMed2001

The impact of unwaged domestic work on the duration and timing of sleep of female nurses working full-time on rotating 3-shift rosters.

The study examined the impact of family type on the timing and duration of sleep of 16 experienced female shiftworkers working a rotating 3-shift roster. The nurses lived in one of three domestic lifestyle arrangements: single with no child care responsibilities (N = 4), partnered with no child care responsibilities (N = 5) and partnered with child care responsibilities (N = 7). Self report sleep diaries were used to collect data over a period of 28 days, following which each nurse took part in a conversational interview. Comparisons of the roster mean sleep durations between groups show that nurses who do not have the added unwaged workload of child care, record significantly more sleep than nurses with such responsibilities. Analysis of the data by shift type shows a significant difference for afternoon shift: nurses with child care responsibilities record a significantly earlier rise time and a significantly shorter total sleep duration. The interview data further highlights how sleep patterns are related to the time constraints of both domestic and waged work.

Adult↗
PubMed2000

Cloning and expression profiling of Hpa2, a novel mammalian heparanase family member.

Heparan sulfate proteoglycans are important constituents of the extracellular matrix and basement membrane. Cleavage of heparan sulfate by heparanase, an endoglycosidase, is implicated in the extravasation of leukocytes and metastatic tumour cells, identifying this enzyme(s) as a target for anti-inflammatory and anti-metastatic therapies. The cloning of a cDNA encoding human heparanase (Hpa1) was reported recently, together with evidence indicating that the hpa1 gene is unique and unlikely to belong to a family of related genes. Here we report the cloning of a cDNA encoding a novel human protein, HPA2, with significant homology to Hpa1. Alternative splicing of the hpa2 transcript yields three different mRNAs, encoding putative proteins of 480, 534, and 592 amino acids. Sequence analyses predict that all three Hpa2 proteins are intracellular, membrane-bound enzymes. Hpa2 also shows a markedly different mRNA distribution to Hpa1 in both normal and cancer tissues. The difference in expression profiles and predicted cellular locations suggests that Hpa2 and Hpa1 proteins have distinct biological functions.

Alternative Splicing↗
PubMed2000

Patterning of polymer-supported metal films by microcutting

The ability to micropattern materials is of great importance for manufacturing advanced electronic, optical and mechanical devices ranging from displays to biosensors. For this purpose a variety of methods have been developed, including X-ray, electron-beam and photo-lithography, microcontact printing, embossing, micromouldings and cold welding. But these techniques are often of restricted applicability, involve a multitude of elaborate and cumbersome processing steps, or require aggressive chemistry. Here we describe a simple and versatile way to create well resolved metallic structures on polymer substrates, which is based on solid-state embossing of metal-coated polymer films. Ductility of both the metal layer and the polymer substrate permits the metal to be cut into surprisingly regular, micrometre-size structures. We illustrate the method by preparing patterned electrically conducting structures, highly efficient infrared polarizers and polarization-dependent colour filters.

Journal Article↗
PubMed2000

National, state, and urban area vaccination coverage levels among children aged 19-35 months--United States, 1998.

PROBLEM/CONDITION: High vaccination levels in the population are necessary to decrease disease transmission and prevent disease; therefore, an important component of the U.S. vaccination program is the assessment of vaccination coverage. Current goals are for > or = 90% coverage with recommended vaccines during the first 2 years of life. REPORTING PERIOD: January-December 1998. DESCRIPTION OF SYSTEMS: The National Immunization Survey (NIS) is an ongoing, random-digit-dialed telephone survey that gathers vaccination coverage data for children aged 19-35 months in all 50 states and 28 urban areas. Vaccination coverage rates derived from NIS data are adjusted statistically for households with multiple telephone lines, household nonresponse, the proportion of households without telephones, and vaccination provider nonresponse. The results were also adjusted to match the known total population of children in each survey area. RESULTS: On the basis of NIS data, national coverage was > or = 90% for three doses of poliovirus vaccine (Polio), three doses of Haemophilus influenzae type b vaccine (Hib), and one dose of measles-containing vaccine (MCV). Coverage was the highest ever reported for four doses of any diphtheria and tetanus toxoids and pertussis vaccine (DTP) (i.e., diphtheria and tetanus toxoids and pertussis vaccine, diphtheria and tetanus toxoids [DT], or diphtheria and tetanus toxoids and acellular pertussis vaccine [DTaP]) (83.9%), three doses of hepatitis B vaccine (Hep B, 87.0%), and one dose of varicella vaccine (43.2%). The number of states achieving the > or = 90% goal was 47 for three doses of Hib, 40 for three doses of Polio, 40 for one dose of MCV, nine for three doses of Hep B, and seven for four doses of DTP. Proportionally fewer urban areas achieved the > or = 90% goal: 23 of 28 for three doses of Hib, 13 for three doses of Polio, 16 for one dose of MCV, five for three doses of Hep B, and one for four doses of DTP. No state or urban area has yet achieved the > or = 90% goal for varicella. INTERPRETATION: Findings from the 1998 NIS indicate that national vaccination coverage levels for routinely recommended childhood vaccines are at the highest levels ever reported. However, substantial variation in coverage remains at the state and urban area levels. PUBLIC HEALTH ACTIONS: The public health community and vaccination providers in areas with low coverage should intensify their efforts to implement recommended strategies for increasing vaccination coverage to ensure that children are equally well protected throughout the United States.

Child, Preschool↗
PubMed2000

Modulating effect of estrogen and testosterone on prostatic stromal cell phenotype differentiation induced by noradrenaline and doxazosin.

BACKGROUND: Noradrenaline (NA) has been shown to enhance expression of the contractile phenotype of human prostatic stromal cells in tissue culture. This study examined the possibility that changing levels of sex hormones in elderly men with BPH may modulate the differentiating effect of NA and hence the efficacy of alpha(1)-adrenoceptor-blocking drugs. METHODS: Confluent, quiescent stromal cell cultures from 6 different patients were treated with combinations of 20 microM NA, 1 microM doxazosin, 0.1 microM beta-estradiol, and 0.1 microM testosterone, over a period of 10 days. Harvested cells were labelled with fluorescein-conjugated antisera to alpha-smooth muscle actin and myosin to identify cells of contractile phenotype which were thereafter analyzed flow-cytometrically. RESULTS: NA increased mean immunoexpression of both actin and myosin. Enhancement of myosin expression was highly significant (P </= 0.02). This effect was incompletely opposed by doxazosin. Neither estradiol nor testosterone influenced mean expression of contractile filaments and did not significantly enhance or inhibit the effects of NA or doxazosin. However, both sex hormones exhibited a differentially powerful effect on cell lines from individual patients. The expression of myosin increased by NA was further elevated by addition of estradiol in four of the cell lines and by testosterone in three. CONCLUSIONS: The data suggest that levels of estrogens and androgens, either alone or in combination, are unlikely to predict the development of obstructive symptoms in patients with BPH or their response to doxazosin. Nevertheless, prostatic stromal cells from individual patients may be exceptionally sensitive to both sex hormones, with enhanced modulation towards a contractile phenotype. Since alpha- and beta-subtypes of the estrogen receptor are differentially expressed between the stroma and epithelium of the early fetal prostate, it is likely that interaction between sex hormones and noradrenaline is an important factor in determining the phenotypic composition of prostatic stroma at this early stage of development, and possibly predisposition to BPH during later adult life.

Actins↗
PubMed2000

A(2A) receptor dependent and A(2A) receptor independent effects of extracellular adenosine on murine thymocytes in conditions of adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency causes severe combined immunodeficiency (SCID) and is accompanied by T-cell depletion and accumulation of both intracellular and extracellular adenosine (extAdo) and deoxyadenosine. To better understand the causes of T-cell depletion in vivo and to discriminate between extracellular and intracellular effects of exogenously added adenosine in vitro, we investigated mechanisms of 2 different effects of adenosine on murine thymocytes. These effects of adenosine include direct induction of apoptosis in about 6% to 15% thymocytes and inhibition of T-cell receptor (TCR)-induced activation of the majority of thymocytes with inhibited ADA. A(2A) adenosine receptors, but not A(2B), A(1), or A(3) receptors, are shown to be mostly responsible for extAdo-triggered signaling (cyclic adenosine monophosphate [cAMP] accumulation) in murine thymocytes and this prompted studies of the effects of extAdo on thymocytes from A(2A)R gene-deficient mice. It is found that direct apoptotic effects of extAdo on CD4(+)CD8(+) double positive (DP) thymocytes are completely accounted for by signaling through A(2A)R, with no contribution of intracellular lymphotoxicity or of compensating A(2B)Rs because only A(2A)R +/+, but not A(2A)R -/- thymocytes were susceptible to apoptotic effects of extAdo. Studies of the effects of cAMP-raising agents support observations of extAdo/A(2A)R/cAMP-triggered apoptosis in DP thymocytes. Unexpectedly, the extAdo strongly inhibited TCR-triggered activation of both A(2A)R +/+ and A(2A)R -/- thymocytes in the presence of ADA inhibitors. This was confirmed with thymocytes from ADA gene-deficient mice, suggesting the existence of A(2A)R-independent effects of extAdo on thymocytes. The presented data raises questions about the identity and functional role of A(2A)R-expressing thymocytes in T-cell differentiation and of the role of TCR-antagonizing effects of extAdo in conditions of ADA SCID. (Blood. 2000;95:3859-3867)

Adenosine↗
PubMed2000

Randomised controlled trial comparing effectiveness of touch screen system with leaflet for providing women with information on prenatal tests.

OBJECTIVE: To compare the effectiveness of touch screen system with information leaflet for providing women with information on prenatal tests. DESIGN: Randomised controlled trial; participants allocated to intervention group (given access to touch screen and leaflet information) or control group (leaflet information only). SETTING: Antenatal clinic in university teaching hospital. SUBJECTS: 875 women booking antenatal care. INTERVENTIONS: All participants received a leaflet providing information on prenatal tests. Women in the intervention arm also had access to touch screen information system in antenatal clinic. MAIN OUTCOME MEASURES: Women's informed decision making on prenatal testing as measured by their uptake of and understanding of the purpose of specific tests; their satisfaction with information provided; and their levels of anxiety. RESULTS: All women in the trial had a good baseline knowledge of prenatal tests. Women in the intervention group did not show any greater understanding of the purpose of the tests than control women. However, uptake of detailed anomaly scans was significantly higher in intervention group than the control group (94% (351/375) v 87% (310/358), P=0.0014). Levels of anxiety among nulliparous women in intervention group declined significantly over time (P<0.001). CONCLUSIONS: The touch screen seemed to convey no benefit over well prepared leaflets in improving understanding of prenatal tests among the pregnant women. It did, however, seem to reduce levels of anxiety and may be most effective for providing information to selected women who have a relevant adverse history or abnormal results from tests in their current pregnancy.

Attitude to Health↗
PubMed2000

Enhancing performance in health care: a theoretical perspective on agency and the role of information.

This paper examines the role of information in securing control of health care systems. The discussion focuses on the impact of the proposed 'Performance Framework', which entails a significant increase in the importance attached to formal performance indicators in the management of the UK National Health Service. The paper starts with a discussion of the role of performance data in securing organizational control within health care systems and summarizes recent research into the behavioural consequences of seeking to control health care agents using such information. A theoretical principal/agent model is then used to illustrate the incentives that exist for dysfunctional behaviour within health care when only imperfect information systems are available. The theoretical results are then examined in the context of a qualitative empirical study, which elicited the perceptions of managers and health care professionals connected with eight NHS hospitals. The study confirmed the existence and importance of serious dysfunctional consequences arising from the use of information as a means of control, and concludes that the Performance Framework will be successful only if it is used in careful conjunction with other means of control.

Delivery of Health Care↗
PubMed2000

Analysis of CDKN1C in Beckwith Wiedemann syndrome.

In this study we have examined 32 patients with Beckwith Wiedemann Syndrome (BWS) for mutations affecting the CDKN1C gene, including seven cases of familial BWS. Mutations were not detected in the coding region of the CDKN1C gene in any individual with BWS. However in two patients, two G/A base substitutions at adjacent positions in the 5'UTR were detected. These substitutions were also found in normal controls. Expression of CDKN1C in somatic tissues was examined in 18 of the 32 cases using semi-quantitative RT-PCR. CDKN1C expression was significantly reduced in the peripheral blood of three cases compared with controls. These results suggest that, although coding region mutations in the CDKN1C gene are rare in BWS, mutations disrupting CDKN1C expression may be found. Three of five informative patients exhibited biallelic CDKN1C expression in lymphocytes, cord blood, and kidney tissue, respectively. Biallelic expression was not associated with overall CDKN1C levels significantly different to those in controls. Patients who expressed CDKN1C biallelically, or who were low CDKN1C expressors, maintained monoallelic methylation in the Differentially Methylated Region 2 (DMR2) of the IGF2 locus. One patient expressing CDKN1C biallelically, maintained imprinted gene expression at the IGF2 locus. These results suggest that biallelic CDKN1C expression does not significantly perturb the overall levels of CDKN1C expression in somatic tissue. They also confirm other studies showing that the mechanisms associated with regulating CDKN1C expression and imprinting are separate from those regulating IGF2 imprinting.

Alleles↗
PubMed2000

Elevated type 1, diminished type 2 cytokines and impaired antibody response are associated with hepatotoxicity and mortalities during Schistosoma mansoni infection of CD4-depleted mice.

During murine Schistosoma mansoni infections parasite eggs evoke a type 2 cytokine-dependent and CD4(+) T cell-mediated granulomatous response in the liver. In this study CD4(+) T cell-depleted CBA / Ca mice developed hepatic steatosis and had high mortalities during early acute schistosome infection. CD4-depleted mice had smaller liver granulomas and reduced hepatic fibrosis. The hepatocytotoxicity was characterized by microvesicular steatosis and neutrophil infiltration. The livers of depleted mice had similar levels of apoptosis as control infected mice but had a marked increase in lipid peroxidation indicative of their livers being under oxidative stress. CD4-depleted mice had impaired egg excretion and exacerbated intestinal pathology. A type 1 cytokine-dominated response was present in infected CD4-depleted mice and relatively reduced production of type 2 cytokines. Antibody responses to parasite antigens were also substantially reduced. Transfer of immune serum or IgG significantly delayed mortalities in depleted mice and prevented hepatocyte damage. Although biasing the cytokine dichotomy to a type 1-dominated response during murine schistosome infection is desirable with respect to certain pathological processes, i. e. it will reduce the granulomatous inflammation and hepatic fibrosis, these effects contribute to fatal pathology if there is reduced protective type 2 cytokines and a defect in antibody responses.

Animals↗
PubMed2000

Genetic enhancement of matrix synthesis by articular chondrocytes: comparison of different growth factor genes in the presence and absence of interleukin-1.

OBJECTIVE: To determine whether articular chondrocytes express growth factor genes delivered by adenoviral vectors and whether expression of these genes influences matrix synthesis in the presence and absence of interleukin-1 (IL-1). METHODS: Monolayer cultures of rabbit articular chondrocytes were infected with recombinant adenovirus carrying genes encoding the following growth factors: insulin-like growth factor 1 (IGF-1), transforming growth factor beta1 (TGFbeta1), and bone morphogenetic protein 2 (BMP-2). As a control, cells were transduced with the lac Z gene. Cultures were also treated with each growth factor supplied as a protein. Levels of gene expression were noted, and the synthesis of proteoglycan, collagen, and noncollagenous proteins was measured by radiolabeling. Collagen was typed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The effects of growth factor gene transfer on proteoglycan synthesis in the presence of IL-1 were also measured. RESULTS: The expression of all transgenes was high following adenoviral transduction. Proteoglycan synthesis was stimulated approximately 8-fold by the BMP-2 gene and 2-3-fold by the IGF-1 gene. The effects of BMP-2 and IGF-1 genes were additive upon cotransduction. Synthesis of collagen and noncollagenous proteins, in contrast, was most strongly stimulated by the IGF-1 gene. In each case, collagen typing confirmed the synthesis of type II collagen. IL-1 suppressed proteoglycan synthesis by 50-60%. IGF-1 and TGFbeta genes restored proteoglycan synthesis to control levels in the presence of IL-1. The BMP-2 gene, in contrast, elevated proteoglycan synthesis beyond control levels in the presence of IL-1. CONCLUSION: Transfer of growth factor genes to articular chondrocytes can greatly increase matrix synthesis in vitro, even in the presence of the inflammatory cytokine IL-1. This result encourages the further development of gene therapy for the repair of damaged cartilage.

Animals↗
PubMed2000

Concordance of the toxicity of pharmaceuticals in humans and in animals.

This report summarizes the results of a multinational pharmaceutical company survey and the outcome of an International Life Sciences Institute (ILSI) Workshop (April 1999), which served to better understand concordance of the toxicity of pharmaceuticals observed in humans with that observed in experimental animals. The Workshop included representatives from academia, the multinational pharmaceutical industry, and international regulatory scientists. The main aim of this project was to examine the strengths and weaknesses of animal studies to predict human toxicity (HT). The database was developed from a survey which covered only those compounds where HTs were identified during clinical development of new pharmaceuticals, determining whether animal toxicity studies identified concordant target organ toxicities in humans. Data collected included codified compounds, therapeutic category, the HT organ system affected, and the species and duration of studies in which the corresponding HT was either first identified or not observed. This survey includes input from 12 pharmaceutical companies with data compiled from 150 compounds with 221 HT events reported. Multiple HTs were reported in 47 cases. The results showed the true positive HT concordance rate of 71% for rodent and nonrodent species, with nonrodents alone being predictive for 63% of HTs and rodents alone for 43%. The highest incidence of overall concordance was seen in hematological, gastrointestinal, and cardiovascular HTs, and the least was seen in cutaneous HT. Where animal models, in one or more species, identified concordant HT, 94% were first observed in studies of 1 month or less in duration. These survey results support the value of in vivo toxicology studies to predict for many significant HTs associated with pharmaceuticals and have helped to identify HT categories that may benefit from improved methods.

Animals↗
PubMed2000

War trauma and psychopathology in Bosnian refugee children.

This paper describes the pattern of psychopathology in a sample of 95 children of 8-13 years, who had experienced war in Bosnia. The children were assessed with a battery of standardised measures during a psychosocial support programme in Northern Greece. They either came from refugee families (44%) or had suffered significant family loss (a parent had been killed in 28% and the father was injured or absent in 27% of cases). Children recalled a substantial number of war traumatic experiences. According to previously established cut-off scores on self-report measures, 45 children (47%) scored within the clinical range on the Depression Self-Rating Scale for Children, 28 (23%) on the Revised Children's Manifest Anxiety Scale, and 65 (28%) on the Impact of Event Scale (IES) measuring PTSD reactions. There was a significant association between the number of war traumatic experiences and the intrusion and avoidance scores on the IES. The findings are discussed in relation to setting up intervention programmes for children victims of war and their families.

Adolescent↗
PubMed2000

Intercusp differences in enamel prism patterns in early and late stages of human tooth development.

Enamel prism-packing patterns reflect the past history of ameloblasts, providing information about growth patterns in tooth development. Here, the area and density of enamel prisms on the cuspal surface of molar teeth were measured to examine if the onset and rate of enamel apposition differ according to stage of development and/or cusp type. Scanning electron-microscopic images were taken from the mesiobuccal and distal cusp tips of 30 mandibular first permanent molars at different stages of development recovered from archaeological sites in Israel dating to the past 10000 years. Selected enamel microstructural characters were measured for each cusp. The mean area of prisms on the mesiobuccal (MB) cusp was significantly larger than that of the distal (D) cusp at all stages of development and the differences in prism area between cusps were significant for each stage of development. Prism density was significantly smaller on the MB cusp than the D cusp at all stages of development but no significant differences were found between early and later stages in each cusp. This was interpreted as indicating that enamel formation in the MB cusp was almost complete, even in the earliest tooth germs studied, whereas in the D cusp it was less advanced. The differences between MB and D cusps are proposed to result from asynchrony of enamel formation between the different cusps of molar teeth in recent populations. The method provides a non-destructive approach to the study of growth patterns in teeth and provides baseline data for comparison with fossil teeth.

Ameloblasts↗
PubMed2000

Crown components of mandibular molar teeth in 45,X females (Turner syndrome).

This study was designed to determine the possible effect of one X-chromosome constitution on components of the human permanent and primary molar teeth. Enamel, dentine, pulp and crown dimensions were measured on radiographs of first and second permanent and second primary mandibular molars of 49 Finnish 45,X females (Turner syndrome), their 46 first-degree male and female relatives and 50 non-related males and females. In permanent first and second molars of the 45,X females, crown width and the dimensions of tooth components were less than those of normal females and males. Reduction in size affected first more than second molars, and in both teeth the enamel was relatively as well as absolutely thinner than in the controls. No differences were found in tooth components between normal relatives and unrelated controls. These data agree with previous studies which have demonstrated that the X chromosome promotes enamel apposition and that both X chromosomes in normal females are active in amelogenesis, while the Y chromosome influences both dentine and enamel growth. The relative reduction in "dentine" or the estimated mesiodistal width of the tooth germ in the 45,X females indicates that their tooth development is affected at an early stage of morphogenesis. Taken together with the results already reported for anterior teeth, the present results suggest that there is an inverse correlation between the duration of crown formation and the severity of size reduction.

Amelogenesis↗
PubMed2000

Fitting in: maintaining a sense of self during hospitalisation.

In this study the patients' perspective of 'fitting in' was gained through participant observation and interviews. Eleven patients' stories confirmed that while hospitalisation can alleviate the suffering caused by illness, it may cause distress. In order to minimise this threat to self patients adjust to hospital life. They are supported by family, friends and health professionals in interpreting the social rules of the ward by conforming to, circumventing and challenging them.

Adaptation, Psychological↗