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Biomedical subjects

P Bell

Publications and source records attributed to P Bell.

At least 19 recordsLinked to original sources
PubMed2005

Migrant status, age, gender and social isolation in very late-onset schizophrenia-like psychosis.

BACKGROUND: Data from two retrospective first contact studies suggest that the risk of developing very-late onset schizophrenia-like psychosis (SLP) may be raised in older migrant than British-born populations resident in the UK. OBJECTIVE: To investigate whether the relative excess of SLP observed amongst younger and male migrants in the above studies might have been explained by differences in the age-gender structures of migrant and British-born denominator populations. A secondary aim was to examine the associations of migrant group status and gender with markers of social isolation. METHOD: Eighty-six new referrals of SLP to the Mile End (1997-2003) and Maudsley (1995-2000) hospitals were identified from two retrospective case note studies. Local census data were used to estimate the denominator populations and to calculate rate ratios for migrant and British-born cases of SLP. Case notes were re-examined, to assess markers of social isolation in migrant and British-born patients. RESULTS: Migrant patients were more likely to be male (odds ratio = 4.8; CI(odds) = 1.8-13.2) than British-born patients. The ratio of first contact rates for migrant compared to British-born populations were highest amongst men. There was a lower mean age of onset of SLP in migrant than British-born patients (t = 4.30, 95% CI = 3.78-10.27), which was largely explained by a higher mean age of illness onset in British-born women. There were no differences between migrant and British-born patients with respect to markers of social isolation. Male patients were more likely to have never married than women (odds ratio = 0.28; 95% CI odds = 0.09-0.89). CONCLUSIONS: The age-gender structure of the background population is not sufficient to explain the socio-demographic differences between migrant and British-born patients with SLP. Male patients may be more socially isolated.

Age of Onset↗
PubMed2002

Deterioration in carotid baroreflex during carotid endarterectomy.

OBJECTIVE: Blood pressure instability after carotid endarterectomy (CEA) has been associated with a disturbance of the baroreflex control mechanism caused by the surgery in the carotid sinus region. The purpose of this study was to determine if a deterioration in carotid baroreceptors occurs during the surgery. METHOD: Heart rate (HR) and blood pressure (BP) were recorded continuously in 60 patients undergoing CEA as well as preoperatively and postoperatively at 2 days and 6 weeks. The baroreflex sensitivity was determined by cross-spectral analysis of HR and systolic blood pressure (SBP). During the surgery, three tests were used to assess the baroreflex response. The first test simulated a sudden fall in systemic blood pressure by clamping the common carotid artery. The second test simulated a rise in systemic blood pressure by applying pressure by using a rubbing action on the luminal surface of the carotid sinus region. The rub test was performed twice, once with the atheromatous plaque in situ and once when the plaque had been removed. The third test is clamp removal and restoration of blood flow through the carotid sinus. RESULTS: Carotid cross-clamping increased mean +/- standard error of the mean SBP from 117 +/- 3 mm Hg before clamping to 125 +/- 3 mm Hg (P <.05) at 30 beats after clamping. The first rub test with the plaque in situ decreased SBP from 121 +/- 3 mm Hg to 117 +/- 3 mm Hg (P <.01) at 10 beats after the rub test, indicating a functioning baroreceptor reflex. The second rub test increased SBP from 126 +/- 3 mm Hg to 128 +/- 3 mm Hg (P <.05). SBP dropped (P <.01) when unclamping suggesting a selective alteration of the baroreflex sensitivity. The baroreflex sensitivity was significantly reduced 2 days postoperatively when compared to preoperative values (P <.05). CONCLUSIONS: These findings suggest that the act of plaque removal could be associated with a partial disruption of baroreceptor mechanism in the carotid artery. This could affect type I baroreceptors.

Aged↗
PubMed2001

Supplementation of islet culture medium with insulin may have a beneficial effect on islet secretory function.

Recent reports suggest that apoptosis resulting from the disruption of the normal cell-matrix relationship (anoikis) during islet isolation could lead to a loss of islet tissue in culture. Insulin is known to have a role in cell growth and survival, and this study was undertaken to assess any beneficial effect on islets by supplementing the islet culture medium with insulin. Human and porcine islets were cultured in medium supplemented with 0, 10, 100, and 1,000 ng x mL(-1) insulin. Secretory function was assessed by perifusion at days 1 and 8. The results demonstrated a significant variation in stimulation index between isolations for human islets, but there was no effect relating to the concentration of insulin in the medium or time in culture. For porcine islets, there was a significant (p < 0.001) improvement in secretory function for islets cultured in 10 and 100 ng x mL(-1) insulin, relative to 0 and 1,000 ng x mL(-1) insulin. There was no interisolation variation or effect of time in culture. In conclusion, the secretory function of porcine islets benefited from the addition of 10 to 100 ng x mL(-1) insulin to the culture medium, but interisolation variation in human islet secretory function did not allow any specific effect of the insulin to be determined.

Animals↗
PubMed2001

Accumulation and intranuclear distribution of unintegrated human immunodeficiency virus type 1 DNA.

The RNA genome of human immunodeficiency virus type 1 (HIV-1) is converted into DNA after infection in order to integrate into the host cell DNA. However, a large number of these reverse-transcribed genomes remain unintegrated in the nucleus of infected cells. Currently, there are no data available about the intranuclear distribution pattern of unintegrated HIV-1 DNA in relation to nuclear structures as observed on the single-cell level. In the present study, we investigated the intranuclear fate of unintegrated viral DNA in cell lines expressing CD4 and coreceptors (HOS-CD4.CCR5 and U373-MAGI-CXCR4(CEM)) infected with HIV-1 (strain 89.6). We used a novel approach to distinguish in situ unintegrated from integrated viral DNA by performing fluorescent in situ hybridization on cells in which stress-induced chromosome condensation had been induced, a procedure that contracts chromosomes independent of the cell cycle. Cells infected for 15 h accumulated large amounts of HIV-1 DNA which was located between the condensed chromosome strands, allowing the identification of this viral DNA as unintegrated. In contrast, in HeLa/LAV, a cell line carrying integrated HIV-1 genomes, the great majority of viral DNA colocalized with the cellular DNA. We show that unintegrated HIV-1 DNA does not evenly distribute within the host cell nucleus but tends to aggregate into clusters containing many copies of the viral genomes. The formation of these DNA clusters was independent of viral DNA replication and thus appeared to result solely from multiple infections. The DNA aggregates remained in the nuclei of infected cells for at least 25 h after the infection was stopped. The emergence of transcription sites, which most likely denote sites of the integrated provirus, lagged clearly behind the accumulation of viral DNA. These transcription foci could not be linked to unintegrated DNA molecules, suggesting that this DNA type is unable to transcribe, at least at levels comparable to those of integrated DNA. Neither unintegrated HIV-1 DNA nor transcription foci nor integrated DNA was observed to associate with nuclear domain 10 (ND10), a nuclear structure known to represent the site where several DNA viruses replicate and transcribe. Also, HIV-1 does not modify ND10 at early or late times of infection. There was no specific association of HIV-1 transcripts with splicing factor SC35 domains, in contrast to what has been reported for a number of both cellular and viral genes. Surprisingly, unintegrated HIV-1 DNA was found to accumulate within or in close association with SC35 domains, demonstrating a specific distribution of the viral DNA within the host cell nucleus. Taken together, our results demonstrate that unintegrated proviral HIV-1 DNA does not randomly localize within infected cells but preferentially aggregates in the nucleus within SC35 domains.

Biological Transport↗
PubMed2001

Cohort studies of health effects among people exposed to estuarine waters: North Carolina, Virginia, and Maryland.

A variety of human symptoms have been associated with exposure to the dinoflagellate Pfiesteria and have been grouped together into a syndrome termed "possible estuary-associated syndrome." Prospective cohort studies of health effects associated with exposure to estuarine waters that may contain Pfiesteria spp. and related organisms are in progress in North Carolina, Virginia, and Maryland. The three studies recruited cohorts of 118-238 subjects who work or engaged in recreation in estuary waters. Baseline health and neuropsychological evaluations are conducted, and study subjects are followed prospectively for 2-5 years with periodic assessments of health and performance on a battery of neuropsychological tests. Health symptoms and estuary water exposure are recorded by telephone interviews or diaries every 1-2 weeks. Water quality information, including measurements of Pfiesteria spp., is collected in the areas where the subjects are working. Because it is not possible to measure individual exposure to Pfiesteria or a toxin produced by this organism, these studies examine surrogate exposure measures (e.g., time spent in estuary waters, in a fish kill area, or in waters where Pfiesteria DNA was detected by molecular amplification). Preliminary analyses of the first 2 years (1998-2000) of data indicate that none of the three ongoing cohorts have detected adverse health effects. However, there have not been any reported fish kills associated with Pfiesteria since the studies began, so it is possible that none of the study subjects have been exposed to toxin-producing Pfiesteria spp.

Animals↗
PubMed2001

Women, war and trauma: a study description.

The last few decades have seen a sharp increase in research into the psychological, psychiatric and social consequences of war. However the bulk of this research relates to male veterans and refugees. There is a serious dearth of literature on female civilians, particularly where the research is being performed in the country of trauma origin. This study aims to explore the psychosocial effects of war on women. One hundred and fifty female civilians participated in this study, conducted in the city of Sarajevo and surrounding refugee settlements in Bosnia. The subjects were divided into three groups: domestic women residing in Sarajevo during and after the war, displaced: women forced to leave their homes, and staying in refugee settlements, returness: women who have returned to Sarajevo from exile. Each woman was interviewed extensively by local psychiatrists. This interview contained the Harvard Trauma Scale for the screening of PTSD and Social Functioning, and the Hopkins Checklist for Anxiety and Depression. Both these tests have been revised, translated and validated for the Bosnian population. The Rosenberg Self-Esteem Scale and the Lazarus Coping scale examine psychological aspects of self-esteem and coping. A questionnaire containing demographic information was devised for the purposes of this study.

Adaptation, Psychological↗
PubMed2000

Review: properties and assembly mechanisms of ND10, PML bodies, or PODs.

Nuclear domain 10 (ND10), also referred to as PML bodies or PODs, are discrete interchromosomal accumulations of several proteins including PML and Sp100. We describe here developments in the visualization of ND10 and the mechanism of ND10 assembly made possible by the identification of proteins that are essential for this process using cell lines that lack individual ND10-associated proteins. PML is critical for the proper localization of all other ND10-associated proteins under physiological conditions. Introducing PML into a PML -/- cell line by transient expression or fusion with PML-producing cells recruited ND10-associated proteins into de novo formed ND10, attesting to its essential nature in ND10 formation. This recruitment includes Daxx, a protein that can bind PML and is highly enriched in condensed chromatin in the absence of PML. The segregation of Daxx from condensed chromatin to ND10 by increased accumulation of Sentrin/SUMO-1 modified PML suggests the presence of a variable equilibrium between these two nuclear sites. These findings identify the basic requirements for ND10 formation and suggest a dynamic mechanism for protein recruitment to these nuclear domains controlled by the SUMO-1 modification state of PML. Additional adapter proteins are suggested to exist by the behavior of Sp100, and Sp100 will provide the basis for their identification. Further information about the dynamic balance of proteins between ND10 and the actual site of functional activity of these proteins will establish whether ND10 function as homeostatic regulators or only in storage of excess proteins destined for turnover.

Animals↗
PubMed2000

Non-apoptotic chromosome condensation induced by stress: delineation of interchromosomal spaces.

Chromosomes are known to occupy distinct territories, suggesting the existence of definite borders. Visualization of these borders requires chromatin condensation like that seen in prophase cells. We developed a novel method to induce chromosome condensation in all cells regardless of cell cycle stage using a complex set of stresses. The cells were not apoptotic, as indicated by the absence of DNA damage, maintenance of the intact lamina and scaffold attachment factor A, and by the continuation of metabolic processes as well as proliferative capacity. That the appearance of chromosome condensation did not represent a premature mitotic event was shown by the absence of fibrillarin and Ki67 envelopment of chromosomes, continued protein synthesis and the reversibility of chromosome condensation. That chromosome condensation was achieved was demonstrated by the removal of chromatin from the nuclear envelope and chromosome painting. Specific genetic sites known to be at the surface of chromosomes retained their positions as shown by in situ hybridization. Stress-induced chromosome condensation was used to prove that specific nuclear domains such as ND10 are interchromosomally located and that green fluorescent protein-tagged ND10-associated proteins are useful markers for chromosomal boundaries after adenovirus 5 track formation in vivo. From these observations we conclude that chromosomal territories appear to have boundaries that exclude developing macromolecular aggregates.

Apoptosis↗
PubMed2000

An exploratory investigation into the housing preferences of consumers of mental health services.

In the present qualitative study, 10 mental health consumers living in the community were interviewed in relation to their housing situations. Three themes emerged from the interview data: 'The place', 'Other consumers' and 'A normal life'. Consumers rejected congregated housing because it enables the larger community to more easily identify them as former psychiatric patients. The views of participants consistently indicate a desire to live a normal life. Results of this study highlight the need for greater consumer participation with mental health nurses and policy makers, in relation to the development of housing services.

Activities of Daily Living↗
PubMed2000

Factors affecting the adhesion of Candida albicans to epithelial cells of insulin-using diabetes mellitus patients.

This study investigated the influence of the carbon source of the growth medium, strains of Candida albicans and source of epithelial cells, and the influence of smoking and gender, on the adhesion of C. albicans to epithelial cells from insulin-using diabetic patients. Adhesion was determined by an autologous adhesion assay with exfoliated buccal or palatal epithelial cells and one strain of C. albicans isolated from each patient. The type strain CBS 562 was also used. Glucose or sucrose were used as the predominant carbon sources of the growth medium. The autologous strain of C. albicans adhered selectively to the oral mucosa of diabetic patients. Palatal epithelial cells retained significantly more C. albicans in vivo and adhesion was influenced by the availability of sugars in the growth medium and the strain of C. albicans.

Candida albicans↗
PubMed2000

Hepatitis delta virus replication generates complexes of large hepatitis delta antigen and antigenomic RNA that affiliate with and alter nuclear domain 10.

Hepatitis delta virus (HDV), a single-stranded RNA virus, bears a single coding region whose product, the hepatitis delta antigen (HDAg), is expressed in two isoforms, small (S-HDAg) and large (L-HDAg). S-HDAg is required for replication of HDV, while L-HDAg inhibits viral replication and is required for the envelopment of the HDV genomic RNA by hepatitis B virus proteins. Here we have examined the spatial distribution of HDV RNA and proteins in infected nuclei, with particular reference to specific nuclear domains. We found that L-HDAg was aggregated in specific nuclear domains and that over half of these domains were localized beside nuclear domain 10 (ND10). At later times, ND10-associated proteins like PML were found in larger HDAg complexes that had developed into apparently hollow spheres. In these larger complexes, PML was found chiefly in the rims of the spheres, while the known ND10 components Sp100, Daxx, and NDP55 were found in the centers of the spheres. Thus, ND10 proteins that normally are closely linked separate within HDAg-associated complexes. Viral RNA of antigenomic polarity, whether expressed from genomic RNA or directly from introduced plasmids, colocalizes with L-HDAg and the transcriptional repressor PML. In contrast, HDV genomic RNA was distributed more uniformly throughout the nucleus. These results suggest that different host protein complexes may assemble on viral RNA strands of different polarities, and they also suggest that this RNA virus, like DNA viruses, can alter the distribution of ND10-associated proteins. The fact that viral components specifically linked to repression of replication can associate with one of the ND10-associated proteins (PML) raises the possibility that this host protein may play a role in the regulation of HDV RNA synthesis.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Replication but not transcription of simian virus 40 DNA is dependent on nuclear domain 10.

DNA viruses from several families including herpes simplex virus type 1, adenovirus type 5, and simian virus 40 (SV40), start their transcription and replication adjacent to a specific nuclear domain, ND10. We asked whether a specific viral DNA sequence determines the location of these synthetic activities at such restricted nuclear sites. Partial and overlapping SV40 sequences were introduced into a beta-galactosidase expression vector, and the beta-galactosidase transcripts were localized by in situ hybridization. Transcripts derived from control plasmids were found throughout the nucleus and at highly concentrated sites but not at ND10. SV40 genomic segments supported ND10-associated transcription only when the origin and the coding sequence for the large T antigen were present. When the large T-antigen coding sequence was eliminated but the T antigen was constitutively expressed in COS-7 cells, the viral origin was sufficient to localize transcription and replication to ND10. Deletion analysis showed that only the large T-antigen binding site II (the core origin) was required but the T antigen was needed for detectable transcription at ND10. Large T antigen expressed from plasmids without the viral core origin did not bind or localize to ND10. Blocking of DNA replication prevented the accumulation of transcripts at ND10, indicating that only sites with replicating templates accumulated transcripts. Transcription at ND10 did not enhance total protein synthesis of plasmid transcripts. These findings suggest that viral transcription at ND10 may only be a consequence of viral genomes directed to ND10 for replication. Although plasmid transcription can take place anywhere in the nucleus, T-antigen-directed replication is apparently restricted to ND10.

Animals↗
PubMed2000

Lytic but not latent replication of epstein-barr virus is associated with PML and induces sequential release of nuclear domain 10 proteins.

Nuclear domains called ND10 (nuclear domain 10) are discrete nuclear protein aggregations characterized by a set of interferon-upregulated proteins including Sp100 and PML, where papova-, adeno-, and herpesviruses begin their transcription and DNA replication. Both the alpha- and betaherpesvirus subfamilies disrupt ND10 upon infection by dispersing and/or destroying ND10-associated proteins. We studied the effect of the gammaherpesvirus Epstein-Barr virus (EBV) on ND10 and its spatial distribution in the nucleus of cells during latency and lytic reactivation. In latently infected Burkitt's lymphoma, lymphoblastoid, and D98/HR1 cells, ND10 were intact, as judged by immunofluorescence localization of PML, Sp100, NDP55, and Daxx. Fluorescent in situ hybridization revealed no association between viral episomes and ND10 during latency, implying that the maintenance replication of EBV, which depends on host cell proliferation, occurs independent of ND10. As in mitosis, the EBV genomes were attached to interphase chromosomes, suggesting that they are unable to move freely within the interchromosomal space and thus unable to associate with the interchromosomally located ND10 or other nuclear domains. Upon lytic activation, ND10 became dispersed in cells expressing lytic proteins. Redistribution of ND10 proteins occurred sequentially at different stages of the lytic cycle, with Sp100, Daxx, and NDP55 dispersed before and PML dispersed after the onset of lytic replication. ND10 remnants were retained until the early stages of lytic replication, and replicating EBV genomes were frequently found beside this nuclear domain; the number of replication domains was usually lower than the average latent virus frequency. Thus, latency does not require or induce interaction of EBV with ND10 for transcription and replication, whereas lytic replication triggers dispersion of ND10 proteins and occurs in close association with PML aggregates. The required movement of chromosome-attached latent EBV episomes to ND10 after reactivation from latency might include physical release of the chromosome-bound episomes. Only episomes contacting ND10 after such a release might be able to begin lytic replication.

Cell Line↗
PubMed2000

Re-survey of the Whitehall study of London civil servants: changes in risk factors for cardiovascular disease during 29 years of follow-up.

BACKGROUND: Substantial uncertainty persists about the relevance of blood pressure and cholesterol to the risk of cardiovascular disease in the elderly. OBJECTIVE: To investigate the determinants of cardiovascular risk in old age, and the relevance of such risk factors when recorded in middle and old age. METHODS: A re-survey in 1997 of 8537 survivors of a cohort of men who were originally examined in 1967-1970 when aged 40-69 years. RESULTS: Completed questionnaires were received from 7050 (82%) of the survivors, and blood pressure and blood samples from 5427 (64%). The response rate declined with increasing age, was inversely related to markers of socioeconomic status in 1967-70 and in 1997, and was lower in those who had been current smokers or had a higher blood pressure level in 1967-70. After excluding those with reported cardiovascular disease (25% of respondents), the mean levels of total cholesterol and apolipoprotein B were lower in older age groups, whereas apolipoprotein A1 levels did not vary much with age. Among those with risk factors recorded both in 1967-70 and 1997, the prevalence of smoking had declined by two-thirds (32% in 1970 and 12% in 1997), the prevalence of diabetes had increased (0.3% versus 4.5%), and the mean systolic blood pressure had increased by 16 mmHg (130 versus 146 mmHg), but the diastolic blood pressure had not changed materially (80 versus 81 mmHg), and the measured levels of total cholesterol had increased by 0.5 mmol/l (although that change may be artefactual). CONCLUSION: Follow-up of vital status in this cohort should permit an assessment of the relevance of risk factors recorded in middle and old age to cardiovascular disease in old age.

Adult↗
PubMed1999

Developmental changes in RNA polymerase I and TATA box-binding protein during early Xenopus embryogenesis.

Xenopus early embryos are transcriptionally quiescent until the midblastula transition (MBT). We have examined the question of whether the absence of rRNA synthesis is related to a deficiency in the RNA polymerase I (pol I) transcription machinery. Previously we have demonstrated that the maternally provided pol I transcription factor UBF already binds to the inactive rRNA genes of pre-MBT embryos (P. Bell et al., 1997, J. Cell Sci. 110, 2053-2063). Here we have analyzed the fate of pol I and the TATA box-binding protein (TBP) through immunofluorescence and immunoblotting experiments. Pol I stockpiled in the egg is taken up by in vitro assembled pronuclei and concentrated into numerous distinct nuclear domains. Comparable storage sites of template-free pol I are also seen in nuclei of blastula to neurula stage embryos. In contrast, the amount of TBP is relatively low in oocytes and eggs but increases dramatically during the cleavage stages. Most of the newly synthesized TBP colocalizes with the stored form of pol I in the extranucleolar domains of blastula/gastrula embryos. The amount of TBP per embryo reaches peak values at the blastula/gastrula stage and then rapidly declines to normal somatic levels. The positive correlation of maximal TBP levels with the timing of the MBT suggests that overproduction of TBP is required for the formation of productive transcription complexes.

Animals↗
PubMed1999

Vascular surgical society of great britain and ireland: transcranial doppler-directed dextran therapy in the prevention of postoperative carotid thrombosis

BACKGROUND: Evidence suggests that embolization precedes carotid thrombosis, a previously unpredictable event complicating 2-3 per cent of all carotid endarterectomies. It was hypothesized that dextran 40 therapy might prevent progression to complete thrombosis in high-risk patients. METHODS: Between October 1995 and July 1998, 400 consecutive patients were monitored following carotid endarterectomy using transcranial Doppler ultrasonography. Those with sustained embolization (more than 25 in 10 min) or those with emboli that distorted the middle cerebral artery waveform were commenced on an incremental dextran 40 infusion. RESULTS: Two hundred and sixteen patients (54 per cent) had one or more emboli detected (96 per cent within 2 h of flow restoration) but only 15 (4 per cent) required dextran therapy. Embolization ceased in each case although the dextran dose had to be adjusted in four. In one of the latter patients, embolization recurred on day 5 but was again controlled with high-dose dextran. Overall, the death and any stroke rate was 2 per cent and no patient suffered a stroke due to carotid thrombosis. CONCLUSION: A few patients develop sustained embolization following carotid endarterectomy which, in previous studies, has been shown to be highly predictive of carotid thrombosis. The authors' experience to date suggests that dextran can stop this phase of embolization and prevent progression to complete carotid thrombosis. However, the dose of dextran has to be adjusted in 25 per cent of patients (i.e. blind administration of dextran may not be effective) and, very rarely, embolization may recur later.

Journal Article↗