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Biomedical subjects

S Bell

Publications and source records attributed to S Bell.

At least 37 records · Page 2Linked to original sources
PubMed1996

An endoplasmic reticulum-retained herpes simplex virus glycoprotein H is absent from secreted virions: evidence for reenvelopment during egress.

Although it is generally accepted that one of the first steps of herpesvirus egress is the acquisition of an envelope by nucleocapsids budding into the inner nuclear membrane, later events in the pathway are not well understood. We tested the hypothesis that the virus then undergoes de-envelopment, followed by reenvelopment at membranes outside the endoplasmic reticulum (ER), by constructing a recombinant virus in which the expression of an essential glycoprotein, gH, is restricted to the inner nuclear membrane-ER by means of the ER retention motif, KKXX. This targeting signal conferred the predicted ER localization properties on gH in recombinant virus-infected cells, and gH and gL polypeptides failed to become processed to their mature forms. Cells infected with the recombinant virus released particles with 100-fold less infectivity than those released by cells infected with the wild-type parent virus, yet the number of enveloped virus particles released into the medium was unaltered. These particles contained normal amounts of gD and VP16 but did not contain detectable amounts of gH, and these data are consistent with a model of virus exit whereby naked nucleocapsids in the cytoplasm acquire their final envelope from a subcellular compartment other than the ER-inner nuclear membrane.

Amino Acid Sequence↗
PubMed1996

I(kappa)B(gamma) inhibits DNA binding of NF-kappaB p50 homodimers by interacting with residues that contact DNA.

NF-(kappa)B is an inducible transcription factor that activates many cellular genes involved in stress and immune response and whose DNA binding activity and cellular distribution are regulated by I(kappa)B inhibitor proteins. The interaction between NF-(kappa)B p50 and DNA was investigated by protein footprinting using chemical modification and partial proteolysis. Both methods confirmed lysine-DNA contacts already found in the crystal structure (K-147, K-149, K-244, K-275, and K-278) but also revealed an additional contact in the lysine cluster K-77-K-78-K-80 which was made on an extended DNA. Molecular modelling of such a DNA-protein complex revealed that lysine 80 is ideally placed to make phosphate backbone contacts in the extended DNA. Thus, it seems likely that the entire AB loop, containing lysines 77, 78, and 80, forms a C-shaped clamp that closes around the DNA recognition site. The same protein footprinting approaches were used to probe the interaction of p50 with the ankyrin repeat containing proteins I(kappa)B(gamma) and I(kappa)B(alpha). Lysine residues in p50 that were protected from modification by DNA were also protected from modification by I(kappa)B(gamma) but not I(kappa)B(alpha). Similarly, proteolytic cleavage at p50 residues which contact DNA was inhibited by bound I(kappa)B(gamma) but was enhanced by the presence of I(kappa)B(alpha). Thus, I(kappa)B(gamma) inhibits the DNA binding activity of p50 by direct interactions with residues contacting DNA, whereas the same residues remain exposed in the presence of I(kappa)B(alpha), which binds to p50 but does not block DNA binding.

Amino Acid Sequence↗
PubMed1996

Sleeping position and upper airways bacterial flora: relevance to cot death.

The hypothesis that the prone sleeping position is associated with accumulation of upper airways secretions and increased bacterial growth was investigated in adults. Ten subjects with upper respiratory tract infection lay prone for one hour and then supine for one hour. Nasal swabs after the prone period yielded higher bacterial counts than swabs obtained after the supine period. This result could be relevant to sudden infant death syndrome (SIDS), as infants who sleep in the prone position are at increased risk of SIDS and one theory is that death is caused by toxins produced by bacterial overgrowth in the upper respiratory tract following a viral infection.

Adult↗
PubMed1996

The management of common dislocations in the upper limb.

Dislocations are among the many orthopaedic injuries that the general practitioner is expected to manage. Many are fairly straightforward to treat, however, there are also many pitfalls. In this paper we provide an overview of the common dislocations in the upper limb, and some that are less common but important to recognise. We have also described the important complications to watch out for and an indication as to which dislocations should be referred for specialist management.

Acromioclavicular Joint↗
PubMed1995

Urinary creatinine adjusted reference ranges for homovanillic and vanillylmandelic acid in children and adults.

The relationship between urinary homovanillic acid (HVA), vanillylmandelic acid (VMA) and creatinine is investigated and reference ranges are constructed for HVA and VMA. A total of 769 urine samples were obtained from children and adults. The ratios HVA/creatinine and VMA/creatinine were highly correlated with creatinine concentration; hence, reference to creatinine was found to be an inappropriate adjustment for urinary dilution. An alternative method based upon linear regression is proposed. After allowing for differing levels of creatinine, HVA and VMA were found to be significantly correlated with age, height and weight for individuals aged less than 20 years. In those aged over 20 years, HVA was significantly correlated with weight and VMA with age. Differences between sexes were found in the levels of HVA and VMA, the exception being VMA in the over 20 age group. Reference ranges were constructed for HVA and VMA which are variously dependent upon creatinine, age, sex and weight.

Adolescent↗
PubMed1995

Cardiac allograft vascular disease. Relationship to microvascular cell surface markers and inflammatory cell phenotypes on endomyocardial biopsy.

BACKGROUND: Cardiac allograft vascular disease is characterized by accelerated and diffuse intimal proliferation involving both the microvasculature and epicardial vessels. Because in vivo documentation of this complication is now possible with intracoronary ultrasound imaging, we can examine the relationship of intimal proliferation to markers of immunity and endothelial activation. We hypothesize that alterations of microvascular cell surface markers likely mirror changes in the epicardial vessels that may be important in the pathophysiology of intimal proliferation. METHODS AND RESULTS: Forty-three heart transplant patients were examined by intracoronary ultrasound more than 1 year after transplantation, and these images were analyzed to obtain mean intimal thickness and intimal thickness class (I through IV), calculated from the mean thickness and circumferential involvement. Right ventricular endomyocardial biopsies obtained at the time of intracoronary ultrasound were examined by immunohistochemistry to detect microvascular expression of histocompatibility leukocyte antigen (HLA) classes I and II (HLA ABC, DR, DP, and DQ); endothelial-specific antigen detected by the monoclonal antibody E 1.5; intercellular adhesion molecules (ICAM-1); CD4+ and CD8+ lymphocytes and macrophages (CD 14+). Microvascular antigen expression was graded 1 through 5 on the basis of the diffuseness of positive staining. The number of each inflammatory cell phenotype present per high-power field was counted. By ANOVA, scores for HLA DR, HLA DQ, and E1.5 expression were lower in intimal thickness classes II, III, and IV compared with class I. This inverse relationship was significant by linear regression analysis of mean intimal thickness. Inflammatory cells were not significantly correlated with intimal thickening. Rejection incidence was higher, and time since transplantation longer, in intimal thickness classes II, III, and IV compared with class I. CONCLUSION: Transplant coronary artery intimal proliferation is associated with alteration of microvascular endothelial cell surface markers. These changes in cell surface antigen expression could provide the substrate for coronary artery intimal proliferation and narrowing.

Adult↗
PubMed1995

Psychological response to cervical screening.

BACKGROUND: Few studies have examined the psychological costs of cervical screening, despite expressed concern over possible negative sequelae. METHODS: Seventy-five women with mild or moderately dyskaryotic smears, under cytological surveillance, 75 women referred for colposcopy after a first-ever abnormal smear showing severe dyskaryosis, and 75 controls with recent negative cytology were interviewed at home, and their psychological adjustment was assessed. RESULTS: Levels of distress were higher among women with an abnormal smear than among controls with a recent negative smear. Anxiety (Hospital Anxiety and Depression Scale range 0-21, "normal" range 0-7) was highest among those referred for colposcopy (mean 8.12, controls 5.88, P < 0.001); afterward, distress fell (mean 6.61, P < 0.001) but more problems of social adjustment were evident (surveillance vs controls, P < 0.01). High anxiety was associated with social maladjustment (colposcopy, P < 0.001; surveillance, P < 0.01) and negative feelings about the self (P < 0.05). Current anxiety was unrelated to knowledge about abnormal smears, but in the surveillance group was related to satisfaction with the explanation provided (P < 0.05). CONCLUSION: A positive cervical smear may by psychologically traumatic for a significant minority of women, irrespective of management strategy.

Adaptation, Psychological↗
PubMed1995

The origin recognition complex in silencing, cell cycle progression, and DNA replication.

This report describes the isolation of ORC5, the gene encoding the fifth largest subunit of the origin recognition complex, and the properties of mutants with a defective allele of ORC5. The orc5-1 mutation caused temperature-sensitive growth and, at the restrictive temperature, caused cell cycle arrest. At the permissive temperature, the orc5-1 mutation caused an elevated plasmid loss rate that could be suppressed by additional tandem origins of DNA replication. The sequence of ORC5 revealed a potential ATP binding site, making Orc5p a candidate for a subunit that mediates the ATP-dependent binding of ORC to origins. Genetic interactions among orc2-1 and orc5-1 and other cell cycle genes provided further evidence for a role for the origin recognition complex (ORC) in DNA replication. The silencing defect caused by orc5-1 strengthened previous connections between ORC and silencing, and combined with the phenotypes caused by orc2 mutations, suggested that the complex itself functions in both processes.

Amino Acid Sequence↗
PubMed1995

A multidisciplinary team approach to day hospital patient care.

A review of practice in a mental health day hospital led to a multidisciplinary quality group being established. Outlines changes implemented leading to service improvements and increases in patient and staff satisfaction.

Community Mental Health Services↗
PubMed1994

False positive results in a neuroblastoma screening programme.

Twenty thousand, eight hundred and twenty-nine babies were screened for neuroblastoma at 6 months of age by measuring homovanillic (HVA) and vanillylmandelic (VMA) acid in urine and rationing these to creatinine. Using a "cut off" of the mean + 3 SD, 10 were found to be positive. Two were found on evaluation to have neuroblastoma and in the remaining 8 the raised levels of HVA and/or VMA returned to normal. Only one of the 8 false positive babies was absolutely normal, most having a chronic disorder or illness. Utilising new centiles which relate HVA and VMA to creatinine, only 3 of the 8 would have remained positive, a false positive rate of 0.01%. The false negative rate would have remained unchanged.

Creatinine↗
PubMed1994

Identification of a gene from Xp21 with similarity to the tctex-1 gene of the murine t complex.

Long range physical mapping within the p21 region of the X chromosome identified a CpG rich island approximately 180 kb centromeric to the chronic granulomatous disease (CGD) locus. The segments adjacent to the CpG island hybridized to discrete bands in DNAs of several species and when used to screen retinal cDNA libraries led to the identification of cDNAs that detected a mRNA of 2.1 kb in many tissues. Molecular characterization of corresponding genomic clones of this novel human gene confirmed the origin of the cDNA clones and indicated a genomic structure with five exons spanning a total of 9 kb. The complete cDNA sequence revealed that this gene contained a putative open reading frame of 116 amino acids with a 3' untranslated region of 1.74 kb. The amino acid sequence shows a high degree of similarity to the predicted product of the tctex-1 gene of the mouse t complex. As linkage studies and patients with deletions have implicated the Xp21 region as containing the retinitis pigmentosa defect (RP3), the gene was assessed as a candidate disease gene in RP3 families. A single base pair polymorphism was identified within the coding region but no disease associated changes were found by single strand conformational polymorphism and sequencing analysis of amplified exons of 20 RP patients. Analysis of a dinucleotide repeat polymorphism within this gene in families affected with RP3 suggested refinement of the RP3 region.

Amino Acid Sequence↗
PubMed1994

An analysis of the in vitro and in vivo phenotypes of mutants of herpes simplex virus type 1 lacking glycoproteins gG, gE, gI or the putative gJ.

Mutants of herpes simplex virus type 1 (HSV-1) lacking glycoproteins gG, gE, gI or the putative gJ were constructed by inserting a lacZ expression cassette within the US4, US8, US7 and US5 genes respectively. Revertant viruses were then constructed by rescue with a wild-type DNA fragment. Each of these mutant viruses, by comparison with the parental virus HSV-1 SC16, exhibited normal particle to infectivity ratios, and had no discernible phenotypic abnormalities in baby hamster kidney-21 cells following high or low multiplicity infections. Infection of mice by scarification of the ear with these mutant viruses showed the following. (i) Interruption of the US5 (gJ) gene has no effect on the ability of HSV-1 to multiply at the inoculation site or its ability to enter or multiply in the peripheral or central nervous system (CNS). This shows that the US5 gene provides a convenient site for the insertion of foreign genes for both in vitro and in vivo studies. (ii) Disruption of the US4 (gG) gene results in marginal attenuation in the mouse ear model. (iii) Disruption of the US7 (gI) or US8 (gE) genes results in pronounced attenuation; virus was rapidly cleared from the inoculation site and was barely detectable in sensory ganglia or in the CNS. The failure of gI-negative or gE-negative viruses to replicate efficiently at the inoculation site in vivo led to the investigation of virus behaviour in epithelial cells in vitro. Viruses lacking gE or gI adsorbed to and entered these cells at normal rates compared with the parental virus, but formed minute plaques. This is consistent with a failure of cell-to-cell spread by the cell contact route. This was confirmed by measurement of the rate of increase in infectious centre numbers following low multiplicity infections. The view that gE and gI influence interactions between cells at the plasma membrane was reinforced by showing that the introduction of disrupted gE or gI genes into a syncytial, but otherwise syngeneic, background resulted in a non-syncytial phenotype. We conclude that the gE-gI complex plays a part, at least in some cell types, in the interactions at the cell surface that allow transmission of the virus from infected to uninfected cells by cell contact. In syncytial strains this leads to uncontrolled membrane fusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Analysis of the contributions of herpes simplex virus type 1 membrane proteins to the induction of cell-cell fusion.

The contributions of a set of herpes simplex virus type 1 membrane proteins towards the process of cell-cell fusion were examined with a series of deletion mutants into which a syncytial mutation had been introduced at codon 855 of the glycoprotein B (gB) gene. Analysis of the fusion phenotypes of these recombinant viruses in Vero cells revealed that while gC, gG, US5, and UL43 are dispensable for syncytium formation at both high and low multiplicities of infection, gD, gHgL, gE, gI, and gM were all required for the fusion of cellular membranes. These data confirm that the requirements for virion entry and cell-cell fusion are not identical. gD and gHgL, like gB, are essential for both processes. gG, gI, and gM, on the other hand, are dispensable for virus penetration, yet play a role in cell-to-cell spread by the direct contact route, at least on an SC16 gBANG background.

Animals↗
PubMed1994

Implementing a research-based protocol: an interactive approach.

Endotracheal suctioning (ETS) is a common procedure done in the critical care environment. There are many different practices related to ETS. With the proliferation of research studies about ETS, a change in practice is needed to incorporate these research findings. The authors present a creative teaching strategy that was used to implement a research-based ETS protocol.

Clinical Nursing Research↗
PubMed1994

Interpractice visits by general practitioners.

Most of the objectives have thus been successfully met as the interpractice visits have proven to be a well accepted form of self-regulated implicit peer review activity among GPs, continuing with enthusiasm on the part of the participants over a period of five years and now propagating nationally. Significant to the success is the ownership of the scheme by the participants. The advent of QA and CE credit points can only enhance participation rates. Continuing attention to the principles of audit, namely evaluation, change and review, will refine the method in the future into an even more effective tool, which can be recommended to all those in general practice. A necessary area for attention in the future is effective outcome evaluation.

Australia↗