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At least 1,261 records · Page 70Linked to original sources
PubMed2003

What features of the home and the area might help to explain observed relationships between housing tenure and health? Evidence from the west of Scotland.

This study aimed to explore the role of dwelling conditions and neighbourhood characteristics in explaining the frequently observed association between housing tenure and health. A postal questionnaire, focusing on a number of specific aspects of the home and the area, was sent to a random sample of adults in the west of Scotland (achieved sample size 2867, response rate 50%). The health measures were limiting long-standing illness, self-assessed health, recent symptoms, and anxiety and depression. Having controlled for age, sex, and marital status, housing tenure explained, respectively, 2.7%, 5.4%, 3.9%, 2.4% and 5.4% of the variance in these variables. These percentages were reduced by between 93% (for anxiety) and 73% (for self-assessed health) when housing problems, housing fixtures, overcrowding, dwelling type, access to garden, area type and area amenities were introduced into the model. This suggests that features of the dwelling and its surroundings help to explain observed associations between tenure and health in the UK, and that housing and area problems may be particularly important. Housing improvements and urban regeneration may help to reduce the health gap between housing tenures, and more generally to reduce inequalities in health.

Adult↗
PubMed1991

Evaluating the sensitivity and predictive value of tests of recent infection: toxoplasmosis in pregnancy.

The diagnosis of maternal infection in early pregnancy depends on tests which are sensitive to recent infection, such as specific IgM. Two types of test are considered: those where the response persists for a period following infection and then declines, such as IgM, and those whose response increases with time since infection, such as IgG-avidity. However, individuals vary in their response to infection, and it may not always be possible to determine whether an infection occurred during pregnancy or before it. Mathematical methods are developed to evaluate the performance of these tests, and are applied to the diagnosis of toxoplasmosis in pregnancy. It is shown that, based on existing information, tests of recent infection are unlikely to be both sensitive and predictive. More data on these tests are required, before they can be reliably used to determine whether infection has occurred during pregnancy or before it.

Animals↗
PubMed1992

Methods for estimating the incidence of primary infection in pregnancy: a reappraisal of toxoplasmosis and cytomegalovirus data.

Accurate incidence information is required to plan and evaluate screening programmes which have been proposed for the detection of primary toxoplasmosis and cytomegalovirus infection in pregnancy. Appropriate statistical methods are described for deriving incidence rates and their confidence intervals from three types of data: change in age-specific seroprevalence, seroconversion, and IgM studies. These methods are applied to seven published studies on toxoplasmosis and cytomegalovirus carried out in the UK. In these publications only one estimate of the infection rate per pregnancy was correctly derived, and none were accompanied by confidence intervals. Using the proposed methods, most estimates of the primary toxoplasmosis rate in these studies were between 2.5 and 5.5 per 1000 pregnancies, compared to the 2 per 1000 usually cited. Most cytomegalovirus incidence estimates were between 4 and 10 per 1000 pregnancies.

Cytomegalovirus Infections↗
PubMed1993

Maternal prevalence of Toxoplasma antibody based on anonymous neonatal serosurvey: a geographical analysis.

A total of 12,902 neonatal samples collected on absorbent paper for routine metabolic screening were tested anonymously for antibodies to toxoplasma. Seroprevalence varied from 19.5% in inner London, to 11.6% in suburban London, and 7.6% in non-metropolitan districts. Much of this variation appeared to be associated with the proportions of livebirths in each district to women born outside the UK. However, additional geographical variation remained and seroprevalence in UK-born women was estimated to be 12.7% in inner London, 7.5% in suburban London, and 5.5% in non-metropolitan areas. These estimates are considerably lower than any previously reported in antenatal sera in the UK. The wide geographical variation highlights a need for further research to determine the relative importance of different routes of transmission.

Antibodies, Protozoan↗
PubMed1996

Risk factors for recent toxoplasma infection in pregnant women in Naples.

Effective primary prevention of congenital toxoplasmosis requires up to date information on locally relevant risk factors for infection in pregnant women. In Naples, risk factors for toxoplasma infection were compared in recently infected women (as assessed by detection of specific IgM in serum) and susceptible, IgG negative women. Recent infection was strongly associated with frequency of consumption of cured pork and raw meat. Eating cured pork or raw meat at least once a month increased the risk of toxoplasma infection threefold. This simple study design for determining locally relevant sources of toxoplasma infection is the first report of cured pork as a risk factor for infection. Further research is required to determine cyst viability in cured pork products. Our findings suggest that in southern Italy, cured pork and raw meat should be avoided by susceptible pregnant women.

Adult↗
PubMed1988

Computer matching of oligonucleotide patterns on electrophoretic gels: an application to the epidemiology of cytomegalovirus.

A computer program was written to analyse oligonucleotide patterns displayed by gel electrophoresis following restriction endonuclease digestion of human cytomegaloviral DNA, and was applied to an epidemiological study of the transmission of infection in a hospital special care baby unit, with regard to infant-to-infant and mother-to-infant transmission. The program calculates the molecular weight of oligonucleotides from their mobilities, using a cubic spline curve based on the mobilities of oligonucleotides from the AD169 strain. A matching algorithm then calculates the number of unmatched fragments for each pair of viral isolates. This was used as a similarity measure which successfully distinguished mother and infant isolate pairs from epidemiologically unrelated pairs. The program is not intended to provide fully automatic matching, but could be recommended as a screening device to pick out pairs of strains which are sufficiently similar to suggest a common source of infection, and which may warrant closer comparison. Other applications are discussed, and the possible use of densitometers to automate data entry is considered.

Algorithms↗
PubMed1999

Non-participation bias in unlinked anonymous HIV-prevalence surveys in England and Wales.

The objective was to assess the potential bias in unlinked anonymous HIV-seroprevalence surveys from objections to specimens being included. Objection rates in seroprevalence surveys were examined. Statistically large clusters of objections were considered to be the result of health care worker behaviour, and were disregarded. Underlying objection rates were estimated from remaining data and compared to seroprevalence. Overall objection rates approached or exceeded seroprevalence in many participating centres. However, underlying objection rates declined with time while prevalences were generally unchanging. Also, underlying rates correlated poorly with observed seroprevalences. Findings were therefore consistent with processes producing the clusters of objections and underlying objection rates independently of serostatus of individuals. Although national seroprevalence estimates produced by the surveys are reasonably free from objection bias, regional seroprevalence estimates outside London remain vulnerable to bias as a result of some centres returning data whose quality cannot be guaranteed.

Bias↗
PubMed2000

HCV prevalence in pregnant women in the UK.

The objective of the study was to assess the prevalence and epidemiology of hepatitis C virus (HCV) infection in pregnant women in the North Thames region, and in the UK in general. Demographic data were linked to neonatal samples prior to anonymization and testing by anti-HCV EIA, and with RIBA 3 confirmation. Risk factors for maternal infection were explored. Area-specific seroprevalence rates were multiplied into population sizes to estimate HCV prevalence in pregnant women in the UK. A total of 241/126,009 samples were confirmed anti-HCV positive, and a further 40 were indeterminate, representing a seroprevalence of 0.19-0.22%; 51% of maternal HCV infections were in UK-born women (71% of the population), and 22% in women from continental Europe (5% of the population). Among European-born women, HCV prevalence was associated with birth in continental Europe, partner not being notified at birth registration, partner born in a different region to the mother, and inner city residence. Four of the 241 anti-HCV positive samples (1.7%) were also anti-HIV-1 positive. It was estimated that each year an estimated 1150 out of 730,000 pregnancies in the UK would involve a woman infected with HCV (uncertainty range 660-1850), a prevalence of 0.16% (0.09-0.25%). On the basis of reported rates of mother-to-child transmission of HCV, this would represent approximately 70 paediatric HCV infections per year.

Adolescent↗
PubMed2006

Carbon-13 labeled polymers: an alternative tracer for depth profiling of polymer films and multilayers using secondary ion mass spectrometry.

13C labeling is introduced as a tracer for depth profiling of polymer films and multilayers using secondary ion mass spectrometry (SIMS). Deuterium substitution has traditionally been used in depth profiling of polymers but can affect the phase behavior of the polymer constituents with reported changes in both bulk-phase behavior and surface and interfacial interactions. SIMS can provide contrast by examining various functional groups, chemical moieties, or isotopic labels. 13C-Labeled PS (13C-PS) and unlabeled PS (12C-PS) and PMMA were synthesized using atom-transfer radical polymerization and assembled in several model thin-film systems. Depth profiles were recorded using a Cameca IMS-6f magnetic sector mass spectrometer using both 6.0-keV impact energy Cs+ and 5.5-keV impact energy O2+ primary ion bombardment with detection of negative and positive secondary ions, respectively. Although complete separation of 12C1H from 13C is achieved using both primary ion species, 6.0-keV Cs+ clearly shows improved detection sensitivity and signal-to-noise ratio for detection of 12C, 12C1H, and 13C secondary ions. The use of Cs+ primary ion bombardment results in somewhat anomalous, nonmonotonic changes in the 12C, 12C1H, and 13C secondary ion yields through the PS/PMMA interface; however, it is shown that this behavior is not due to sample charging. Through normalization of the 13C secondary ion yield to the total C (12C + 13C) ion yield, the observed effects through the PS/PMMA interface can be greatly minimized, thereby significantly improving analysis of polymer films and multilayers using SIMS. Mass spectra of 13C-PS and 12C-PS were also analyzed using a PHI TRIFT I time-of-flight mass spectrometer, with 15-keV Ga+ primary ion bombardment and detection of positive secondary ions. The (12)C7(1)H7 ion fragment and its 13C-enriched analogues have significant secondary ion yields with negligible mass interferences, providing an early indication of the potential for future use of this technique for cluster probe depth profiling of high molecular weight 13C-labeled fragments.

Journal Article↗
PubMed1995

Specificity of minor-groove and major-groove interactions in a homeodomain-DNA complex.

To assess the importance of minor-groove and major-groove interactions in homeodomain-DNA recognition, the binding properties of variants of the altered-specificity engrailed homeodomain, containing Lys50, and its DNA site TAATCC were determined. This homeodomain contacts bases in the minor groove of the DNA using Arg3 and Arg5 from its N-terminal arm and contacts bases in the major groove of the DNA using Ile47, Lys50, and Asn51 from its third alpha-helix. Mutation of Arg3 or Ile47 to alanine reduces binding affinity 10-20-fold while mutation of Arg5, Asn51, or Lys50 to alanine reduces binding affinity > 100-fold, indicating that both minor-groove and major-groove interactions contribute to the overall binding energy. Binding site selections and affinity measurements show that the homeodomain can also discriminate among different base pairs in the minor groove and the major groove. However, the interactions between Lys50 of the recognition helix and the major-groove edges of base pairs 5 and 6 are more specific than interactions mediated by Arg3 and Arg5 in the N-terminal arm and the minor-groove edges of base pairs 1 and 2.

Alanine↗
PubMed1994

Differential DNA-binding specificity of the engrailed homeodomain: the role of residue 50.

To assess the importance of residue 50 in determining the binding specificity of the homeodomain from the engrailed transcription factor of Drosophila, the DNA-binding properties of isolated homeodomains containing glutamine (wild type), alanine, and lysine at this position have been studied. In binding site selection experiments using the wild-type engrailed homeodomain, TAATTA was identified as a high-affinity, consensus binding site. When the glutamine at position 50 was replaced by a lysine (QK50), the binding site preference changed to TAATCC. The half-life and affinity of the complex between the QK50 protein and a DNA site containing TAATCC were increased significantly compared to the half-life and affinity of the complex between the wild-type protein and a TAATTA site. This suggests that Lys50 forms a more favorable interaction with the TAATCC DNA than Gln50 does with the TAATTA site. In fact, the wild-type Gln50 side chain (which forms a hydrophobic interaction with the last A:T base pair of the TAATTA site in the cocrystal structure [Kissinger, C. R., Liu, B., Martin-Blanco, E., Kornberg, T. B., & Pabo, C. O. (1990) Cell 63, 579-590]) appears to play only a small role in determining binding affinity and specificity for the TAATTA site, as the QA50 mutant has only a 2-fold reduced affinity for the TAATTA site and discriminates between the TAATTA and TAATCC sites as well as the wild-type protein. As a result, determinants in addition to Gln50 must be involved in establishing the differential binding specificity of the engrailed homeodomain.

Amino Acid Sequence↗
PubMed2004

Overexpression of the endoplasmic reticulum 60 protein ER-60 downregulates apoB100 secretion by inducing its intracellular degradation via a nonproteasomal pathway: evidence for an ER-60-mediated and pCMB-sensitive intracellular degradative pathway.

Co- and posttranslational regulation of apolipoprotein B (apoB) has been postulated to involve degradation by both proteasomal and nonproteasomal pathways; however, nonproteasomal mechanisms of apoB degradation are currently unknown. We have previously demonstrated an intracellular association of newly synthesized apoB with endoplasmic reticulum (ER)-60, an ER-localized protein, possessing both proteolytic and chaperone activities. In the present paper, adenoviral expression vectors containing rat ER-60 cDNA were used to achieve dose- and time-dependent overexpression of ER-60 to investigate its role in apoB100 turnover. Overexpressed ER-60 accumulated in the microsomal lumen of HepG2 cells and was associated with apoB100 in dense lipoprotein particles. Overexpression of ER-60 in HepG2 cells significantly reduced both intracellular and secreted apoB100, with no effect on the secretion of a control protein, albumin. Similar results were obtained in McA-RH7777 rat hepatoma cells. ER-60-stimulated apoB100 degradation and inhibition of apoB100 secretion were sensitive to the protease inhibitor, p-chloromercuribenzoate (pCMB), in a dose-dependent manner but were unaffected by the proteasomal or lysosomal protease inhibitors, N-acetyl-leucinyl-leucinyl-nor-leucinal, E64, and leupeptin. Interestingly, enhanced expression of ER-60 induced apoB100 fragmentation in permeabilized HepG2 cells and resulted in detection of a unique 50 kDa degradation intermediate, a process that could be inhibited by pCMB. Intracellular stability and secretion of apoB100 in primary hamster hepatocytes were also found to be sensitive to pCMB. When taken together, the data suggest an important role for ER-60 in promoting apoB100 degradation via a pCMB-sensitive process in the ER. ER-60 may act directly as a protease or may be involved indirectly as a chaperone/protein factor targeting apoB100 to this nonproteasomal and pCMB-sensitive degradative pathway.

Adenoviridae↗
PubMed2005

Oleate-mediated stimulation of microsomal triglyceride transfer protein (MTP) gene promoter: implications for hepatic MTP overexpression in insulin resistance.

Hepatic lipoprotein overproduction in a fructose-fed hamster model of insulin resistance was previously shown to be associated with a significant elevation of intracellular mass of microsomal triglyceride transfer protein (MTP) and elevated plasma levels of free fatty acids (FFA). Here, we further establish that fructose feeding and development of an insulin resistant state result in higher levels of MTP mRNA, protein mass, and lipid transfer activity. MTP protein mass was increased in fructose-fed hamster hepatocytes to 161 +/- 35.8% of control (p < 0.05), while MTP mRNA levels and MTP lipid transfer activity were increased to 147.5 +/- 30.8% (p < 0.05) and 177.5 +/- 14.5% (p < 0.05) of control levels, respectively. To identify underlying mechanisms, we also investigated the potential link between enhanced FFA flux and hepatic MTP gene expression. Direct modulation of MTP gene transcription by fatty acids was investigated by transfecting HepG2 cells with a reporter (luciferase) construct containing various base pair regions of the human MTP promoter including pMTP124 (with the sterol response element (SRE)), pMTP116, pMTP109 and pMTP100 (no SRE), and pMTP124SREKO (SRE sequences mutated). Treatment of HepG2 cells with oleic acid (360 muM) significantly increased luciferase activities in cells transfected with pMTP124 (136.6 +/- 11.0%, p < 0.05) and pMTP124SREKO (153.9 +/- 11.1%, p < 0.01) compared with control. Luciferase activity was also increased in a time and dose-dependent manner in the presence of oleic acid when transfected with pMTP124SREKO but not pMTP109 and pMTP100. Furthermore, long-term oleic acid treatment of HepG2 cells (10 days) induced higher levels of MTP mRNA (p < 0.05) confirming transcriptional stimulation of the MTP gene by oleic acid. In contrast, palmitate, arachidonic acid or linoleic acid did not significantly stimulate pMTP124 or pMTP124SREKO luciferase activity (p > 0.05). These data demonstrate that (1) MTP gene transcription may be directly up-regulated by oleic acid; (2) up-regulation of MTP gene transcription by oleic acid is SRE sequence independent; and (3) the sequence -116 to -109 in the MTP promoter region is essential for oleic acid-mediated stimulation. Stimulation of MTP gene expression may be a novel mechanism by which certain FFAs can induce hepatic lipoprotein secretion in insulin resistant states.

Animals↗
PubMed2004

Translational control of apolipoprotein B mRNA: regulation via cis elements in the 5' and 3' untranslated regions.

Translational control of apolipoprotein B (apoB) mRNA has been previously documented; however, the molecular mechanisms that govern translation of apoB mRNA are unknown. We investigated the role of the untranslated regions (UTR) in the regulation of apoB mRNA translation first by analyzing apoB UTR sequences using M-fold, a program used to predict RNA secondary structure. M-fold analysis revealed hairpin-like elements within the 5'UTR and 3'UTR of apoB mRNA with potential to form stable secondary structure. Luciferase (LUC) reporter assays were conducted to assess the biological activity of the putative RNA motifs within the UTR sequences by transiently transfecting HepG2 cells with chimeric mRNAs containing the 5' and/or 3' apoB UTRs linked to a LUC reporter gene. We observed statistically significant increases in LUC activity for the 5'UTRpGL3 and 5'/3'UTRpGL3 constructs. LUC mRNA levels remained constant for all constructs, suggesting that increased LUC activity was likely posttranscriptional in nature. When RNA isolated from transfected cells was translated in vitro, parallel increases in translatable LUC activity were observed. We also examined the role of UTR sequences within the context of the apoB coding sequence, using constructs containing the N-terminal 15% of apoB (apoB15). We observed a 40% and 25% increase in total protein mass with the 5'UTR-apoB15 construct and the 5'UTR-apoB15-3'UTR, respectively, over the control construct with no apoB UTR, with only a slight stimulation observed for apoB15 3'UTR. Radiolabeling analysis of apoB15 synthetic rate showed a more striking 4.5-fold stimulation of protein synthesis by 5'UTR while addition of both UTRs caused a 3.1-fold stimulation over the control construct. Deletion mutant analysis revealed that the stimulatory effect of the 5'UTR on apoB mRNA translation may be dependent on specific hairpin elements formed within the 5'UTR secondary structure. Overall, our data suggest that putative 5'UTR motifs are important for optimal translation of the apoB message whereas the presence of the 3'UTR appears to attenuate wild-type expression. Potential cis-trans interactions of these motifs with putative RNA binding proteins/translational factors are likely to govern apoB mRNA translation and protein synthesis and may play an important role in dysregulation of atherogenic lipoprotein production in dyslipidemic states.

3' Untranslated Regions↗
PubMed2005

Insulin-mediated suppression of apolipoprotein B mRNA translation requires the 5' UTR and is characterized by decreased binding of an insulin-sensitive 110-kDa 5' UTR RNA-binding protein.

Insulin has been shown to acutely regulate hepatic apolipoprotein B (apoB) secretion at both translational and post-translational levels; however, mechanisms of apoB mRNA translational control are largely unknown. Recent studies of apoB untranslated regions (UTRs) revealed a potentially important role for cis-trans interactions at the 5' and 3' UTRs. In the present paper, deletion constructs of the UTR regions of apoB revealed that the 5' UTR was necessary and sufficient for insulin to inhibit synthesis of apoB15. Metabolic radiolabeling and in vitro translation experiments in the presence of protease inhibitors confirmed that the effect of insulin on the apoB 5' UTR was translational in nature. Using the nondenaturing electrophoretic mobility shift assay (EMSA), protein-RNA complexes were detected binding to the apoB 5' and 3' UTRs. Denaturing EMSA identified a 110-kDa protein interacting at the 5' UTR. Nondenaturing EMSA determined that insulin altered binding of large protein complexes to the 5' UTR. Binding specificity was determined by competition with both specific and nonspecific competitors. Insulin treatment decreased binding of the 110-kDa protein to the 5' UTR as visualized by EMSA. Absence of insulin increased binding of this trans-acting factor to the 5' UTR by 2-fold. Analysis of the 3' UTR showed no significant insulin-mediated changes in binding of trans-acting factors. We thus propose the existence of a novel RNA-binding insulin-sensitive factor that binds to the 5' UTR and may regulate apoB mRNA translation. Perturbations in hepatic insulin signaling as observed in insulin-resistant states may alter cis-trans interactions at the 5' UTR, leading to alterations in the rate of apoB mRNA translation, thus contributing to apoB-lipoprotein overproduction.

5' Untranslated Regions↗
PubMed2005

Effect of chemical speciation on toxicity of mercury to Escherichia coli biofilms and planktonic cells.

While it is known that microbial uptake of mercury (Hg) by planktonic cultures is influenced by the extracellular speciation of mercury in aquatic systems, Hg uptake in biofilm cultures is understudied. We compared the importance of Hg(II) speciation in toxicity to both planktonic and biofilm cultures of the Gram-negative bacterium Escherichia coli 055. Variable chloride chemistry experiments were carried out to modify mercury speciation. Biofilms were observed to be more resistant to Hg than planktonic cells. In both planktonic and biofilm cultures, the toxicity of Hg increased and then decreased along the chloride gradient. The percent reduction in cell viability was linearly related to the concentration of HgCl2(0) when Hg-chloro complexes dominated the speciation, consistent with a passive diffusion model. However, toxicity to both planktonic cells and biofilms at low salinities could not be explained by passive diffusion alone, which suggests that microbial uptake of Hg in both planktonic cells and biofilms may occur by both passive diffusion of neutral species and facilitated uptake. The relationship between toxicity and chloride concentration was similar in the presence and absence of a biofilm, indicating that the presence of the biofilm does not drastically change the relative availability of the dominant mercury species.

Biofilms↗