Search PubMed⌕ Search

Biomedical subjects

S Bell

Publications and source records attributed to S Bell.

At least 73 records · Page 4Linked to original sources
PubMed1997

S. cerevisiae and sulfur: a unique way to deal with the environment.

Saccharomyces cerevisiae is by far the best-studied unicellular eukaryote. Although yeast cells are very similar to higher eukaryotes in many respects, there is striking evidence that S. cerevisiae is not a perfect model for a eukaryotic cell (cf. 1). Here we report that yeast proteins contain a significantly lower amount of cysteine residues compared to other eukaryotes. Explanations for this phenomenon could not be found in the sulfur metabolism of yeast, which showed no major differences from other organisms (2-4). However, previous examinations could link a defect in sulfate uptake of S. cerevisiae to an increased resistance against toxic substances like selenate and chromate in the environment, which share the same permeases (5-7). This environmental problem might have caused S. cerevisiae to down-regulate its sulfate uptake and therefore lead to a lower amount of available sulfur in the cell, making it necessary to replace all dispensable sulfur amino acids in proteins. We show in two examples that S. cerevisiae proteins contain only such cysteine residues that are structurally or functionally needed. Therefore, we conclude that S. cerevisiae has solved a widespread environmental problem in a specific way which might be unique among eukaryotes.

Base Sequence↗
PubMed1997

Site-directed and linker insertion mutagenesis of herpes simplex virus type 1 glycoprotein H.

The gH-gL complex of herpes simplex virus type 1 (HSV-1) is essential for virion infectivity and virus-induced cell fusion, but functional domains of the gH molecule remain to be defined. We have addressed this question by mutagenesis. A set of linker insertion mutants in HSV-1 gH was generated and tested in transient assays for their ability to complement a gH-negative virus. Insertions at three sites in the C-terminal third of the external domain affected the ability of gH to function in cell-cell fusion and virus entry, while insertions at six sites in the N-terminal half of the external domain induced conformational changes in gH such that it was not recognized by monoclonal antibody LP11, although expression at the cell surface was unchanged. A recombinant virus in which a potential integrin-binding motif, RGD, in gH was changed to the triplet RGE entered cells as efficiently as the wild type, indicating that HSV-1 entry is not mediated by means of the gH-RGD motif binding to cell surface integrins. Furthermore, mutagenesis of the glycosylation site which is positionally conserved in all herpesvirus gH sequences in close proximity to the transmembrane domain generated a recombinant virus that grew in vitro with wild-type single-step kinetics.

Animals↗
PubMed1997

Prevention of hepatitis A and B.

The vaccine preventable hepatitides, hepatitis A and hepatitis B, cause a great burden of illness in both developing and industrialized nations. There is increased community awareness of the problems of viral hepatitis, and it is important for general practitioners to be aware of current recommendations for prevention of hepatitis A and B.

Adolescent↗
PubMed1996

An Mll-AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: a method to create fusion oncogenes.

Homologous recombination in embryonal stem cells has been used to produce a fusion oncogene, thereby mimicking chromosomal translocations that frequently result in formation of tumor-specific fusion oncogenes in human malignancies. AF9 sequences were fused into the mouse Mll gene so that expression of the Mll-AF9 fusion gene occurred from endogenous Mll transcription control elements, as in t(9;11) found in human leukemias. Chimeric mice carrying the fusion gene developed tumors, which were restricted to acute myeloid leukemias despite the widespread activity of the Mll promoter. Onset of perceptible disease was preceded by expansion of ES cell derivatives in peripheral blood. This novel use of homologous recombination formally proves that chromosomal translocations contribute to malignancy and provides a general strategy to create fusion oncogenes for studying their role in tumorigenesis.

Acute Disease↗
PubMed1996

Neonatal osteofibrous dysplasia: report of two cases.

Skeletal neoplasms of the newborn and neonatal period are infrequently encountered and often misdiagnosed. Osteofibrous dysplasia is a tumor of childhood that may be seen in the newborn. Because of its unique natural history, with and without surgical treatment, and the similarity in radiographic appearance of this tumor to other lesions, a high index of suspicion must be maintained when a tibial lesion is encountered in the newborn. We present two additional cases of neonatal osteofibrous dysplasia and discuss the differential diagnostic considerations.

Diagnosis, Differential↗
PubMed1996

Improving outpatient clinic staffing and scheduling with computer simulation.

Patient flow in an appointment-based, outpatient internal medicine clinic involving multiple, sequential providers-registrar, triage nurse, physician, and discharger-was studied using computer simulation. Provider task time distributions were obtained through a time-motion study and then input into the computer program, which simulated the clinic situation well. Time interval and sensitivity analyses yielded insights into staffing levels, appointment times, and clinic dynamics. A bottleneck provider was shown, and patient time in the clinic was related to the time of appointment and was slowed by having too many doctors in the clinic. Subsequent operational changes significantly decreased the average observed patient total time in clinic from 75.4 (SD 34.2) minutes to 57.1 (SD 30.2) minutes (p < .001, t test).

Appointments and Schedules↗
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↗