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Biomedical subjects

K Harrison

Publications and source records attributed to K Harrison.

At least 19 recordsLinked to original sources
PubMed2006

Dwarfism and cytochrome P450-mediated C-6 oxidation of plant steroid hormones.

BRs (brassinosteroids) are plant steroid hormones that are essential for normal plant development. The dramatic dwarfism exhibited by mutants in the CYP (cytochrome P450) enzymes involved in BR biosynthesis indicates a role for these hormones in plant growth and development. Since the mid-1990s, collaborative research has been geared towards developing a better understanding of the CYP85 class of CYPs involved in BR biosynthesis in both Arabidopsis and tomato. Some of the most recent observations include the fact that certain CYP85 CYPs catalyse the synthesis of the most bioactive BR, BL (brassinolide). Current evidence suggests that evolution of this function may have occurred independently in different dicotyledonous species. Interestingly, BL accumulates in tomato fruits, highlighting a key role for this hormone in fruit development. At the same time as developing a better understanding of the enzymatic function of these CYPs, we have also carried out experiments towards characterizing where and when these genes are expressed and mechanisms of their regulation. As expected for a hormone involved in growth and development, biosynthetic gene promoter activity is associated with young rapidly growing cells and with fruit development.

Arabidopsis↗
PubMed2006

Potential cervical spine injury and difficult airway management for emergency intubation of trauma adults in the emergency department--a systematic review.

BACKGROUND: Emergency airway management for trauma adults is practised by physicians from a range of training backgrounds and with differing levels of experience. The indications for intubation and technique employed are factors that vary within EDs and between hospitals. OBJECTIVES: To provide practical evidence based guidance for airway management in trauma resuscitation: first for the trauma adult with potential cervical spine injury and second the management when a difficult airway is encountered at intubation. SEARCH STRATEGY AND METHODOLOGY: Full literature search for relevant articles in Medline (1966-2003), EMBASE (1980-2003), and the Cochrane Central Register of Controlled Trials. Relevant articles relating to adults and written in English language were appraised. English language abstracts of foreign articles were included. Studies were critically appraised on a standardised data collection sheet to assess validity and quality of evidence. The level of evidence was allocated using the methods of the Australian National Health and Medical Research Council.

Adult↗
PubMed2004

Regulators of G protein signaling: potential drug targets for controlling cardiovascular and immune function.

Heterotrimeric G-protein-coupled receptors (GPCRs) mediate a wide variety of organismal functions ranging from vision, olfaction, and gustation to the development and physiology of the cardiovascular, neuronal, and immune system. Naturally they are targets of a large number of therapeutic drugs. The regulators of G protein signaling (RGS) are a family of diverse proteins that regulate the GPCR-mediated signaling pathways principally by acting as GTPase activating proteins (GAPs) for the alpha subunit of the heterotrimeric G-proteins. Certain members of the RGS family contain multiple domains and motifs that mediate interactions with other signaling molecules, thus linking GPCR-dependent and GPCR-independent signaling pathways. Because of their ability to fine-tune vital GPCR-mediated processes and recent findings linking them to brain disorders, retinitis pigmentosa, and cancer RGS proteins have become excellent candidates for new drug discovery. The focus of this review is to discuss the roles of the RGS proteins in the development and normal physiology of cardiovascular and immune system, and to explore their potential as drug targets useful for the treatment of pathological conditions of the cardiovascular and immune systems.

Animals↗
PubMed2003

Current practice for induction of labour in the United Kingdom: time for a review?

This paper presents the results of postal survey of protocols for induction of labour. The drug regimes used for the induction of labour in NHS hospitals in England and Wales have been compared to both RCOG guidelines and to the drug manufacturer's recommendations. A wide variation in practice was found, with many units using dosages that are different from those recommended. The implications of such departures from the norm are discussed in terms of the importance of evidence-based practice and the role of national guidelines in ensuring optimum care.

Female↗
PubMed2002

Developmental control of promoter activity is not responsible for mature onset of Cf-9B-mediated resistance to leaf mold in tomato.

Cf-9 confers resistance to tomato seedlings and mature plants against Cladosporium fulvum races expressing the Avr9 elicitor. It is the central member of a cluster of five paralogous genes in an introgressed segment of chromosome 1 derived from Lycopersicon pimpinellifolium. The other four genes have been named Hcr9-9A, Hcr9-9B, Hcr9-9D, and Hcr9-9E. Hcr9-9B, here designated Cf-9B, encodes weaker resistance than Cf-9, recognizes a different elicitor, and protects only mature plants from infection. The onset of Cf-9B-mediated resistance and the molecular basis for its developmental control were investigated in this study. Fungal inoculation of tomato plants containing reciprocal Cf-9/Cf-9B promoter-coding region swaps, analysis of tomato plants containing promoter-gusA fusions, and a reverse transcriptase-polymerase chain reaction study of Cf-9 and Cf-9B transcripts in tomato plants suggested that transcriptional control of Cf-9B did not account for the late onset of Cf-9B-mediated resistance. Alternative explanations for the onset of Cf-9B-mediated resistance in mature plants are discussed.

Base Sequence↗
PubMed2001

Identification of selective inhibitors of cyclin dependent kinase 4.

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.

Carbazoles↗
PubMed2001

Methylation of HpaII site at the human DXS16 locus on Xp22 as an assay for abnormal patterns of X inactivation.

The highly polymorphic human DXS16 locus on Xp22 contains a BglII restriction fragment length polymorphism with 33% heterozygosity. We report that methylation of the HpaII site, 3.1 kb away from this restriction fragment length polymorphism, correlates with X-inactivation. The BglII polymorphism distinguishes between the maternal and paternal alleles, and HpaII digestion identifies their methylation status. The accuracy of this assay was tested on more than 30 control females and some patients with known patterns of X-inactivation. The data obtained from this assay agree substantially with those obtained using the androgen receptor assay, which is widely used for detecting patterns of X-inactivation. This is the first marker on Xp22 found to be suitable for clonal analysis. Of additional significance is this marker's proximity to the pseudoautosomal boundary on the X chromosome and its potential use in identifying rare events occurring in this region, which lead to escape from normal X-inactivation.

Alleles↗
PubMed2001

Cryptic duplication of 21q in an individual with a clinical diagnosis of Down syndrome.

We describe an adult male who was diagnosed with Down syndrome (DS) at 9 months of age, but had repeatedly normal karyotypes until recent mid-resolution chromosome studies showed a possible duplication of 21q22.13 to 21q22.3. The abnormality was investigated using fluorescent in situ hybridization (FISH) studies. These showed hybridization of a whole chromosome paint probe (wcp21, Oncor Coatasome 21) to the entire length of both chromosome 21 homologues and one very large hybridization signal of a cosmid contig probe localized within bands 21q22.13-21q22.2(LSI-21, Vysis) on the ?dup(21q) homologue. CGH analysis identified a ratio of 1.5 for the segment of chromosome 21 involving band 21q22, indicating a gain of part, or all, of the terminal band of chromosome 21. The karyotype was thus defined as 46,XY,?dup(21) (q22.13q22.2).ish dup(21)(LSI-21++,wcp21+). Common DS characteristics in our case and 12 previously reported cases with duplications involving chromosome 21 included mental retardation, fifth finger clinodactyly, open mouth and oblique eye fissures. Transverse palmar creases and congenital heart defects, seen in DS less than 40% of the time, were infrequent. Presence of these features did not appear to depend on the specific portion of chromosome 21 that was duplicated. A review of 18 additional clinical features showed no consistent phenotype-genotype correlations.

Adult↗
PubMed2001

Comparative analysis of multiple-casualty incident triage algorithms.

STUDY OBJECTIVE: We sought to retrospectively measure the accuracy of multiple-casualty incident (MCI) triage algorithms and their component physiologic variables in predicting adult patients with critical injury. METHODS: We performed a retrospective review of 1,144 consecutive adult patients transported by ambulance and admitted to 2 trauma centers. Association between first-recorded out-of-hospital physiologic variables and a resource-based definition of severe injury appropriate to the MCI context was determined. The association between severe injury and Triage Sieve, Simple Triage and Rapid Treatment, modified Simple Triage and Rapid Treatment, and CareFlight Triage was determined in the patient population. RESULTS: Of the physiologic variables, the Motor Component of the Glasgow Coma Scale had the strongest association with severe injury, followed by systolic blood pressure. The differences between CareFlight Triage, Simple Triage and Rapid Treatment, and modified Simple Triage and Rapid Treatment were not dramatic, with sensitivities of 82% (95% confidence interval [CI] 75% to 88%), 85% (95% CI 78% to 90%), and 84% (95% CI 76% to 89%), respectively, and specificities of 96% (95% CI 94% to 97%), 86% (95% CI 84% to 88%), and 91% (95% CI 89% to 93%), respectively. Both forms of Triage Sieve were significantly poorer predictors of severe injury. CONCLUSION: Of the physiologic variables used in the triage algorithms, the Motor Component of the Glasgow Coma Scale and systolic blood pressure had the strongest association with severe injury. CareFlight Triage, Simple Triage and Rapid Treatment, and modified Simple Triage and Rapid Treatment had similar sensitivities in predicting critical injury in designated trauma patients, but CareFlight Triage had better specificity. Because patients in a true mass casualty situation may not be completely comparable with designated trauma patients transported to emergency departments in routine circumstances, the best triage instrument in this study may not be the best in an actual MCI. These findings must be validated prospectively before their accuracy can be confirmed.

Adolescent↗
PubMed2001

Subcellular localization and targeting of glucocorticoid receptor protein fusions expressed in transgenic Arabidopsis thaliana.

An animal system of inducible activation of protein fusions with the binding domain of glucocorticoid receptor (BDGR) was tested in Arabidopsis thaliana by monitoring dexamethasone (DEX)-induced nuclear targeting of reporter constructs. Two constructs containing green fluorescent protein (GFP), human homeobox protein Hanf-1 and Xenopus laevis BDGR were used, GFP/Hanf-1/BDGR and GFP/BDGR. The control construct contained GFP alone. In the absence of DEX both fusion proteins were uniformly distributed in the cytoplasm of root cells, but showed strong association with plastids in plant aerial parts. DEX treatment of roots prompted a strong and reversible nuclear accumulation of GFP/Hanf-1/BDGR, but not GFP/BDGR. Thus, in roots, the specific nuclear translocation of GFP/Hanf-1/BDGR was driven by Hanf-1 and tightly regulated by BDGR. However, in plant aerial parts treated with DEX, nuclear translocation of GFP/Hanf-1/BDGR was observed only in a few cases, and most part of the fusion protein was incorrectly and irreversibly targeted to plastids. Protease X digestion of isolated chloroplasts showed that BDGR fusion proteins were translocated into the chloroplast envelope and bound to envelope membranes, probably due to association with the chloroplast import apparatus. Thus, for efficient use of the glucocorticoid-inducible system in plants, it will be necessary to modify BDGR structure to prevent incorrect targeting of fusion proteins.

Animals↗
PubMed2001

Role of IFN-gamma in bacterial containment in a model of intra-abdominal sepsis.

Interferon-gamma (IFN-gamma) is a specific activator of macrophage function and plays a critical role in the host immune defense to bacterial infection. In this study we examined the role of IFN-gamma in the regulation of bacterial load in the cecal ligation and puncture (CLP) model of intra-abdominal sepsis in the rat. In initial studies, levels of IL-12, MCP-1, and IFN-gamma were measured in the peritoneal lavage fluid 24 and 48 h after CLP. IL-12 and MCP-1 levels were both significantly increased at 24 h after CLP compared to sham controls and this difference was maintained at 48 h after CLP. Interestingly, IFN-gamma levels were not significantly increased 24 h after CLP, but were increased at 48 h after CLP. These results clearly suggest that although an inflammatory response had occurred 24 h post-surgery, with increases in the proinflammatory cytokine IL-12 and the potent chemotactic agent MCP-1, levels of IFN-gamma in CLP rats were similar to sham controls. To further investigate the role of IFN-gamma on the development of sepsis we examined the effect(s) of administering anti-IFN-gamma antibody on bacterial load after CLP. We show that use of anti-IFN-gamma antibody can significantly decrease bacterial load in the peritoneum. The mechanism of the effect(s) of anti-IFN-gamma is probably by increasing intestinal adhesions to seal the cecum and reduce bacterial movement into the peritoneum.

Animals↗
PubMed2000

TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease.

B cells are important in the development of autoimmune disorders by mechanisms involving dysregulated polyclonal B-cell activation, production of pathogenic antibodies, and co-stimulation of autoreactive T cells. zTNF4 (BLyS, BAFF, TALL-1, THANK) is a member of the tumour necrosis factor (TNF) ligand family that is a potent co-activator of B cells in vitro and in vivo. Here we identify two receptors for zTNF4 and demonstrate a relationship between zTNF4 and autoimmune disease. Transgenic animals overexpressing zTNF4 in lymphoid cells develop symptoms characteristic of systemic lupus erythaematosus (SLE) and expand a rare population of splenic B-Ia lymphocytes. In addition, circulating zTNF4 is more abundant in NZBWF1 and MRL-lpr/lpr mice during the onset and progression of SLE. We have identified two TNF receptor family members, TACI and BCMA, that bind zTNF4. Treatment of NZBWF1 mice with soluble TACI-Ig fusion protein inhibits the development of proteinuria and prolongs survival of the animals. These findings demonstrate the involvement of zTNF4 and its receptors in the development of SLE and identify TACI-Ig as a promising treatment of autoimmune disease in humans.

Amino Acid Sequence↗
PubMed2000

Predicting early adolescent substance use: do risk factors differ depending on age of onset?

This study was designed to identify different risk models associated with non-use, first use, and prior substance use among a group of early adolescents. A total of 582 students completed a self-report questionnaire at the beginning and end of sixth grade. Nine predictor variables were used in discriminant function analysis to classify adolescents into three groups. Five variables distinguished non-users (never used by the end of sixth grade) and new users (first used during sixth grade) from prior users (first used before sixth grade). Prior users were found to have weaker decision making skills, more susceptibility to peer pressure, more negative perceptions of school, less confidence in their skills, and an increased likelihood of being male. A second function indicated that new users were similar to prior users in that they had less positive peer relations, were more likely to come from single parent families, and had less knowledge about alcohol and drugs than did non-users. The similarities and differences between new and prior users have implications for future research and prevention programming.

Adolescent↗
PubMed2000

High-dose therapy with 90Yttrium-labeled monoclonal antibody CC49: a phase I trial.

A Phase I trial of increasing administered activities of 90yttrium (90Y)-labeled monoclonal antibody (MAb) CC49 was conducted to determine whether extrahematopoietic toxicity occurred with this radioimmunoconjugate. Twelve patients with various gastrointestinal tract cancers were administered a tracer dose of 111In-labeled MAb CC49 for biodistribution and pharmacokinetic studies. Patients then underwent a single treatment with increasing administered activities of 90Y-labeled MAb CC49 (0.3, 0.4, and 0.5 mCi/kg). Biodistribution studies, using 111In-labeled MAb CC49 as a surrogate, were determined using planar and single photon emission computed tomography imaging. Pharmacokinetic studies were performed by measuring radioactivity in blood samples taken at intervals after radioimmunoconjugate infusions. Tissue biopsies of tumor metastases and related normal tissues (liver and bone marrow) were obtained for radioactivity measurements. Radiation dosimetry estimates were calculated using these data. Toxicity was evaluated using the National Cancer Institute Common Toxicity Criteria. No dose limiting extrahematopoietic toxicity was identified in the range of administered activities used in this study. Radioimmunolocalization based on planar and single photon emission computed tomography images 111In-labeled MAb CC49 showed heterogeneous (nonspecific) liver and splenic uptake. Liver metastases were usually photopenic, and extrahepatic metastases showed faint to moderate uptake. The alpha and beta half-lives of 111In-labeled MAb CC49 and 90Y-labeled MAb CC49 in the blood were similar. Absorbed radiation dose estimates in metastatic tumor sites ranged from 180 to 3000 cGy. The percentage of injected dose/kg of tumor ranged from 1.12 to 18.14; however, tumor:normal liver ratios were consistently <1. No objective responses were observed. Doses of up to 0.5 mCi/kg could be administered with reversible grade IV myelotoxicity. Absorbed radiation dose in tumor was suboptimal, even at the highest administered activity level. Deposition of 90Y in liver was high, and estimates of absorbed dose in liver equaled or exceeded that which could be achieved in metastatic tumor sites. Strategies to enhance access of radioimmunoconjugates in tumor and diminish deposition in the liver need to be developed for effective treatment using MAb CC49 with chelated radiometals.

Adenocarcinoma↗
PubMed2000

Beneath the veil--health records in the Middle East.

The healthcare industry is a fast-growing, dynamic industry within the UAE today. It is a basic necessity that is constantly changing in line with advancing technology, and the need to provide the right service to the right patient at the right time. The MAT programme aims to provide its students with the education necessary to enable them to meet and exceed the needs of these demands. The three cornerstones of this programme will ensure that this is achieved, as with quality, standards and confidentiality for clear signposts to industry relevance, the students cannot fail to reach their potential.

Certification↗