Biomedical subjects
Publications and source records attributed to J Monks.
Explore the source record for details and available documents.
We have identified novel nuclear transcripts in the human beta-globin locus using nuclear run-on analysis in erythroid cell lines and in situ hybridization analysis of erythroid tissue. These transcripts extend across the LCR and intergenic regions but are undetectable in nonerythroid cells. Surprisingly, transient transfection of a beta-globin gene (epsilon, gamma, or beta) induces transcription of the LCR and intergenic regions from the chromosomal beta-globin locus in nonerythroid cell lines. The beta-globin genes themselves, however, remain transcriptionally silent. Induction is dependent on transcription of the globin gene in the transfected plasmid but does not require protein expression. Using in situ hybridization analysis, we show that the plasmid colocalizes with the endogenous beta-globin locus providing insight into the mechanism of transinduction.
Poly(A) signals of mammalian pre-mRNA have been defined as an AAUAAA sequence 10-30 nt upstream of the cleavage/poly(A) site followed by a GU/U-rich element immediately downstream. However, a number of viral poly(A) signals have been shown to possess additional signals upstream of AAUAAA that increase poly(A) site efficiency. We describe the first non-viral example of such an upstream sequence element (USE) for the poly(A) site of the human C2 complement gene. As this gene is very closely spaced to the related Factor B gene [the C2 poly(A) site is only 421 bp from the transcription start site of Factor B] we have isolated this same intergenic sequence from four other mammals (mouse, cat, rabbit and cow). We show that the USE of the C2 poly(A) site is highly conserved between these five different mammals. Furthermore, extensive mutagenesis of the human USE indicates that most of the 53 nt sequence is required for full activity. The human C2 poly(A) site does not possess any obvious downstream GU/U-rich sequences, although sequences immediately 3' to AAUAAA as well as 13 nt of sequence following the cleavage site are both required for full activity. Interestingly the other mammalian C2 poly(A) sites do possess significant downstream GU/U-rich sequences. Finally we show that all five mammalian C2 poly(A) signals are immediately followed by conserved signals for transcriptional termination, consistent with the close proximity of the downstream Factor B gene.
This paper concerns how a 'performance' perspective may aid our understanding of life story data in the investigation of sickness experience. The argument is illustrated through structural and thematic analysis of the life story of a young English woman with multiple sclerosis (MS). The life story genre allowed the author creatively to explore contrasting perspectives on the shaping of social relations by bodily disorder. This was in the context of her more general concerns about definition and change in social relationships and the physical body. Performance relates the form and content of the story to generative social experience as well as to multiple readings and reformulations. It thus gives insight into the constitutive processes through which bodily knowledge is produced and shared in relation to notions of person and self.
Meeting the community care needs of elderly people at home requires close co-ordination of health and social services input. Social worker Jonathan Monks and health visitor Lou Illesley report on how they work together to plan and deliver effective packages of care to elderly people registered with the GP practice to which they are both attached.
We demonstrate that multiple SP1 protein:DNA binding sites confer enhancer-independent activation on the HIV-1 and globin gene promoters. This activation process can be achieved either by DNA replication of the promoter-containing plasmid or by high concentrations of input plasmid DNA used in the transfections. In the case of HIV-1, the three SP1 sites adjacent to the promoters TATA box are essential for this activation process. Furthermore, the human beta globin gene, which is normally dependent on a linked enhancer for transcriptional activity, can be made enhancer independent by insertion of SP1 binding sites adjacent to its TATA box. We speculate that (SP1)n-TATA type RNA polymerase II promoters may be generally permissive when present on actively replicating DNA templates and that this property of the HIV-1 promoter may be of importance to the activation of the DNA provirus in latently infected T cells.
To investigate the selective use of poly(A) sites in the 3' long terminal repeat (LTR) but not the 5' LTR of retroviruses, we have studied the poly(A) site of the human immunodeficiency virus (HIV-1). Using hybrid HIV/alpha-globin gene constructs, we demonstrate that the HIV poly(A) site is inactive or occluded when adjacent to an active promoter, either the homologous HIV promoter or the alpha-globin gene promoter. Furthermore, this occlusion of the HIV poly(A) site occurs over a considerable distance of up to at least 500 bp. In contrast, two nonretroviral poly(A) sites [alpha-globin and a synthetic poly(A) site] are active when close to a promoter. We also show that a short fragment of approximately 60 nucleotides containing the HIV poly(A) site is fully active when placed at the 3' end of the human alpha-globin gene or within the rabbit beta-globin gene. This result rules out the requirement of more distant upstream elements for the activity of the HIV poly(A) site, as has been suggested for other viral poly(A) sites. Finally, we show that the GT-rich downstream region of the HIV poly(A) site confers poly(A) site occlusion properties on a synthetic poly(A) site. This result focuses attention on this more variable part of a poly(A) site in retroviruses as a possible general signal for poly(A) site occlusion.
The criteria which may be employed by chronically ill people in their decision about whether to continue with therapy were investigated in the context of a clinical trial of hyperbaric oxygen therapy for multiple sclerosis. An open-ended question about reasons for continuing or discontinuing treatment obtained data from 48 trial participants on completion of the trial and six months later. Physical factors were the most commonly cited reasons for continuing treatment; stabilization of the condition was mentioned as well as improvement. Lack of effectiveness was more commonly given as a reason to stop therapy six months after the trial. Social and practical reasons were also cited as reasons for discontinuing therapy and there was implicit evidence of a high level of social support enabling patients to continue therapy. Most problems appeared to have surfaced by the end of the trial. Epistemological reasons provided rationales for the decisions taken and referred particularly to the time required to make an informed judgement about the effectiveness of treatment. Personal experience and knowledge of the effects of hyperbaric oxygen on others were more significant to the decision than anticipation of the trial's formal results. The participants in the trial were sophisticated and responsible decision-makers even though their judgements would not always have coincided with medical opinion.
Problems with case ascertainment in epidemiological research on multiple sclerosis (MS) make it necessary to use indirect sources. However, there is a lack of information about the characteristics of cases drawn from different sources and thus little basis on which sampling frames for large scale surveys may be constructed. The characteristics of a population drawn from the membership of Action for Research into Multiple Sclerosis (ARMS) were compared with those of 10 other British MS populations reported between 1980 and 1987. Demographic variables examined were geographical location, nationality, ethnicity, sex ratio and age. Diagnostic status, age at diagnosis and duration since diagnosis were considered together with data on the comparative populations based on date of onset. On all the variables investigated the ARMS population fell close to or within the range shown by the comparative populations. The relative youth of the ARMS population and its bias towards a high proportion of females were differences in keeping with existing knowledge about the membership of mutual support organisations. A population drawn from such an organisation may usefully complement other MS research populations provided that the likely biases in each are understood.
Explore the source record for details and available documents.
The interaction between imipenem, a carbapenem antibiotic, and two representative beta-lactamases has been studied. The first enzyme was beta-lactamase I, a class-A beta-lactamase from Bacillus cereus; imipenem behaved as a slow substrate (kcat. 6.7 min-1, Km 0.4 mM at 30 degrees C and at pH 7) that reacted by a branched pathway. There was transient formation of an altered species formed in a reversible reaction; this species was probably an acyl-enzyme in a slightly altered, but considerably more labile, conformation. The kinetics of the reaction were investigated by measuring both the concentration of the substrate and the activity of the enzyme, which fell and then rose again more slowly. The second enzyme was the chromosomal class-C beta-lactamase from Pseudomonas aeruginosa; imipenem was a substrate with a low kcat. (0.8 min-1) and a low Km (0.7 microM). Possible implications for the clinical use of imipenem are considered.
Inclusion of subjective measures in clinical trials has raised questions concerning the basis on which their results may be compared with medical findings. Central problems relate to the status of such measures as indicators of 'real' change and to appropriate methods of assessing their significance. These issues were explored in a controlled trial of hyperbaric oxygen therapy (HBO) for multiple sclerosis (MS). Subjective measures were incorporated on the basis of an explicit view of their status vis à vis medical assessments. The General Health Questionnaire (GHQ) and Nottingham Health Profile (NHP) were investigated with respect to their usefulness as indicators of the significance of reported benefit. While neither measure appeared sensitive to the kinds of significance involved, the NHP in particular might have a role in identifying orders of effectiveness which remain untapped by more commonly employed measures of perceived improvement.
An understanding of the influences upon nurses' time distribution is important for the evaluation of care and the justification of the cost of the nursing service. Time devoted to the care of breast cancer patients at different stages of their illness was studied by direct observation in ward, theatre and outpatient departments. Factors affecting the time spent with patients were found to differ in each location. In the ward and theatre, nurses' work was primarily patient-orientated in that the most significant determinants of the amount of nurse-patient contact appeared to be characteristics of the patients themselves. Particularly in the ward, nurses seemed free to make their own decisions concerning the patients who most needed their attention. In outpatient departments, organizational factors and the characteristics of the doctors conducting the clinics seemed most significant in determining nurses' time distribution. However, there were signs that nurses recognize differences between patients to which their current pattern of work organization does not allow adequate response.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
This paper examines the various ways in which symptoms of chronic illness may be experienced. With particular reference to fatigue in multiple sclerosis, it discusses how the conceptualization of symptoms as discrete entities requiring targeted action (common in much current writing on chronic illness) is only one form in which physical disorder may be recognized by those directly affected, and one which probably applies little in the course of everyday life. The paper draws attention to the significance of personal and social context in symptom definition and to the implications for the measurement of symptoms and for advice to patients on management.