Biomedical subjects
Publications and source records attributed to C R Burton.
A new structural type of kinase inhibitor, containing a benzocarbazole nucleus, has been identified. Members of the series are selective for inhibition of the cyclin dependent kinase family of enzymes. Although the cdks are highly homologous, representatives of the series showed intra-cdk selectivities, especially for cdk4. SAR studies elucidated the important features of the molecules for inhibition.
Quinazolines have been identified as inhibitors of CDK4/D1 and CDK2/E. Aspects of the SAR were investigated using solution-phase, parallel synthesis. An X-ray crystal structure was obtained of quinazoline 51 bound in CDK2 and key interactions within the ATP binding pocket are defined.
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A theoretical description of the nursing role in stroke rehabilitation remains elusive in the literature. The United Kingdom strategy for health service development will increasingly require nurses from all clinical specialities to collaborate with other health care professionals and stakeholders to evaluate the services they provide. In stroke rehabilitation, an understanding of the contribution that nursing makes is essential, if that collaboration is to be effective. This paper details a study undertaken to describe the nature of the nursing role in stroke rehabilitation, and the factors that shape this role. A reflective enquiry was used to enable the collection of data grounded in the realities of clinical practice. Study participants were qualified nursing staff (n=13) working in a rehabilitation unit in the north-west of England. A total of 35 in-depth reflections were obtained for analysis. Three role categories were identified in the data: the nurse as care giver, facilitator of personal recovery and care manager. Sub-categories of nursing intervention were identified within each category, together with anticipated outcomes and contextual features that shaped the category. The results of the study were verified by a purposive sample of nursing staff from the rehabilitation unit.
Understanding how stroke sufferers experience their stroke and recovery is essential if the development of rehabilitation services is to be effective and appropriate. Previous research in this area has tended to be either cross-sectional or with a limited amount of informant follow-up, and consequently has limited utility. This paper describes a study underpinned by a phenomenological approach, which tracked the experiences of six patients admitted to a rehabilitation unit in the north-west of England. Informants were followed for at least 12 months after stroke, and a total of 73 interviews were undertaken during the study. The data demonstrate that recovery from stroke involved restructuring and adaptation in physical, social and emotional aspects of an individual's life. Two important features of recovery were highlighted. First, whilst aspects of pre-stroke life may be used to describe individual progress, no end-point to recovery was identified as informants described and anticipated life with stroke. Second, informants focused on the social context of recovery where engagement in the social world was emphasized over discrete physical function. Although no common path of recovery was found, it is recommended that stroke services are structured to take account of the long-term needs of stroke patients and their families in their home environment.
Re-thinking stroke rehabilitation: the Corbin and Strauss chronic illness trajectory framework The dramatic effects of a stroke can have far-reaching implications for patients and carers. Effective recovery involves a considerable array of coping strategies that facilitate and promote engagement in the social world. Their development is a long-term process that requires considerable effort, motivation and enterprise on the part of patients and their families. Traditional approaches to the provision of stroke rehabilitation services, however, appear to be underpinned by frameworks that are short-term in outlook. As a consequence, nursing interventions often focus on the progression of the patient through the care system, rather than on facilitating future recovery. Much of the work of stroke recovery is consequently done by patients and their families at home, with little provision of ongoing professional help and advice. This paper explores the application of the Corbin and Strauss Chronic Illness Trajectory Framework for stroke. In particular, the major concepts of the framework are applied to a vignette derived from a longitudinal study of patients' experiences of recovery. The trajectory framework is shown to be a useful structure that has the potential to enhance the appropriateness of nursing interventions for stroke patients. However, the validity of the framework can only be established through its application and evaluation in clinical practice. The purpose of this paper is to contribute to a debate that encourages consideration of the framework's utility for nurses to enhance the stroke rehabilitation experience.
Although there is knowledge of the substantial benefits of collaborative approaches to stroke rehabilitation, information on alternative management strategies is sparse. This paper describes an exploratory survey, undertaken in the north-west of England, to highlight features of the stroke co-ordinator role. The role is explored in terms of rehabilitation management and service development. Some strategies to support practitioners in the role, and areas for role development, are suggested.
The objective of this study was to determine whether the three isoforms of recombinant Ang II receptors (rAT1A, rAT1B and hAT1), stably and individually expressed in CHO cells, could be pharmacologically distinguished by their ligand binding signatures. Competition studies were performed to characterize the inhibition of [125I]Ang II binding to each of the cell membrane preparations by an extensive series of peptide and nonpeptide Ang II analogs. Scatchard plot analyses revealed the following binding characteristics:rAT1A-Kd = 1.27 +/- 0.14 nM; rAT1B- Site 1:Kd = 0.56 +/- 0.11 nM, Site 2: Kd = 126 +/- 23 nM; and hAT1-Site 1:Kd = 1.06 +/- 0.16 nM, Site 2: Kd = 257 +/- 55 nM. The binding of [125I]Ang II in the three preparations was similarly sensitive to inhibition by GTP gamma S. The ligand binding signatures of the three receptor isoforms are essentially the same and are illustrated by the affinity and order of potency of the following ligands: L-158,809 > or = Sar1, Ile8Ang II > saralasin Ang II > or = Ang III > EXP581 > EXP3174 > losartan > or = EXP811 > GR117,289c > EXP6803 > DuP 532 > Ang I >> PD123177. In conclusion, the two rat AT1 receptor isoforms are pharmacologically indistinguishable from each other and from that of the human.
The infectious laryngotracheitis virus (ILTV) homologue of the herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) gene was identified by PCR amplification of genomic ILTV DNA. A 488-bp amplified DNA fragment was used to identify and clone two adjacent PstI fragments from genomic ILTV DNA. Sequence analysis of the region surrounding the amplified fragment identified a 2619-bp open reading frame that has 39% homology with both the nucleotide and amino-acid sequences of the HSV-1 gB gene. Northern blot analysis using a portion of the open reading frame as a probe identified a 2.7-kb RNA transcript in ILTV-infected chicken embryo liver cells. Analysis of the predicted amino acid sequence of the ILTV protein indicated that it shares structural features with the gB glycoproteins of other herpesviruses.
An an initial step in the development of a recombinant poultry infectious laryngotracheitis virus (ILTV) vaccine, we report on the identification, cloning, and sequencing of a thymidine kinase (tk) gene from a virulent U.S. field isolate of ILTV. Degenerate oligonucleotide primers for the consensus nucleotide (ATP) binding site and the nucleoside (thymidine) binding site of other herpesvirus tk genes were used in the polymerase chain reaction (PCR) to amplify a fragment of ILTV DNA. The 344-base-pair (bp) amplified fragment was cloned into plasmid pKSII and used in Southern hybridizations to locate the ILTV tk gene on a 2.4-kb HindIII fragment. Upon cloning and sequencing this fragment, a 1089-bp open reading frame was identified, which is predicted to encode a protein demonstrating 27.9% amino acid homology to the herpes simplex virus type 1 (HSV-1) thymidine kinase protein. Analysis of the sequence revealed one region of difference from that reported for the Thorne strain of ILTV. In addition, the portion of the TK protein corresponding to the nucleotide binding domain is highly conserved among the avian herpesviruses.