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Biomedical subjects

Karen Moore

Publications and source records attributed to Karen Moore.

9 recordsLinked to original sources

Mammalian cell delivery via aerosol deposition.

The objective of this study was to test the hypothesis that bovine dermal fibroblasts can survive aerosol delivery via an airbrush with mean cell survival rates greater than 50%. This technology has great implications for burn and other wound therapies, for delivery of genetically altered cells in gene therapies, and for tissue engineering with tissue scaffolds. Bovine dermal fibroblasts were suspended at a concentration of 200,000 cells/mL in Hank's Balanced Salt Solution, and delivered into six-well tissue culture plates using a Badger 100G airbrush. Cells were delivered through three nozzle diameters (312, 484, and 746 microm) at five different air pressures (41, 55, 69, 96, and 124 kPa). Nine repetitions were performed for each treatment group, and cell viability was measured using trypan blue exclusion assay. Mean cell viability ranged from 37 to 94%, and depended on the combination of nozzle diameter and delivery pressure (p < 0.0001). Linear regression analysis was used to develop a stochastic model of cell delivery viability as a function of nozzle diameter and delivery air pressure. This study demonstrates the feasibility of using an airbrush to deliver viable cells in an aerosol to a substrate.

Aerosols↗

Increasing smoking cessation care in a preoperative clinic: a randomized controlled trial.

BACKGROUND: Evidence suggests that preoperative clinics, like other hospital outpatient clinics and inpatient wards, fail to systematically provide smoking cessation care to patients having planned surgery. METHODS: The aim of the study was to assess the efficacy, acceptability, and cost of a multifaceted intervention to facilitate the provision of comprehensive smoking cessation care to patients attending a preoperative clinic. Two hundred ten smoking patients attending a preoperative clinic at a major teaching hospital in Australia took part in the study. One hundred twenty-four patients were randomly assigned to an experimental group and 86 patients to a usual cessation care group. A multifaceted intervention was developed that included the use of opinion leaders, consensus processes, computer-delivered cessation care, computer-generated prompts for care provision by clinic staff, staff training, and performance feedback. RESULTS: Ninety-six percent of experimental group patients received behavioral counseling and tailored self-help material. Experimental group patients were significantly more likely than usual care patients to report receiving brief advice by nursing (79% vs. 47%; P < 0.01) and anaesthetic (60% vs. 39%; P < 0.01) staff. Experimental group patients who were nicotine dependent were also more likely to be offered preoperative nicotine replacement therapy (NRT) (82% vs. 8%; P < 0.01) and be prescribed postoperative NRT (86% vs. 0%; P < 0.01). The multifaceted intervention was found to be acceptable by staff. CONCLUSION: A multifaceted clinical practice change intervention may be effective in improving the delivery of smoking cessation care to preoperative surgical patients.

Adult↗

Fission yeast Cdc23 interactions with DNA replication initiation proteins.

Schizosaccharomyces pombe Cdc23 is an essential DNA replication protein, conserved in eukaryotes and functionally homologous with Saccharomyces cerevisiae Dna43 (Mcm10). We sought evidence for interactions between Cdc23 and the MCM2-7 complex, a component of both the pre-replicative complex and the replication fork. Cdc23 shows genetic interactions with four MCM subunits: cdc23-M36 and cdc23-1E2 alleles both show synthetic phenotypes with mcm2 (cdc19-P1) and mcm6 (mis5-268), and cdc23-M36 is synthetically lethal with mcm4 (cdc21-K46) and with mcm5 (nda4-108). The wild-type cdc23 gene on multicopy plasmids can partially suppress temperature-dependent defects in mcm5 (nda4-108). Two-hybrid analysis demonstrates interactions at the protein-protein level between Cdc23 and Mcm4, Mcm5 and Mcm6. Cdc23 also interacts with four subunits of the Schizosaccharomyces pombe origin recognition complex (ORC) in yeast two-hybrid assay: Orc1, Orc2, Orc5 and Orc6. We found no evidence for interaction between Cdc23 and the MCM recruitment factor Cdc18 (the homologue of Saccharomyces cerevisiae Cdc6). Unlike Cdc18, Cdc23 mRNA shows no significant fluctuation in level through the cell cycle. These data suggest that fission yeast Cdc23 is an MCM-associated factor which has a role in the initiation of DNA replication.

Anaphase-Promoting Complex-Cyclosome↗

NH3-dependent NAD+ synthetase from Bacillus subtilis at 1 A resolution.

The final step of NAD+ biosynthesis includes an amide transfer to nicotinic acid adenine dinucleotide (NaAD) catalyzed by NAD+ synthetase. This enzyme was co-crystallized in microgravity with natural substrates NaAD and ATP at pH 8.5. The crystal was exposed to ammonium ions, synchrotron diffraction data were collected and the atomic model was refined anisotropically at 1 A resolution to R = 11.63%. Both binding sites are occupied by the NAD-adenylate intermediate, pyrophosphate and two magnesium ions. The atomic resolution of the structure allows better definition of non-planar peptide groups, reveals a low mean anisotropy of protein and substrate atoms and indicates the H-atom positions of the phosphoester group of the reaction intermediate. The phosphoester group is protonated at the carbonyl O atom O7N, suggesting a carbenium-ion structure stabilized by interactions with two solvent sites presumably occupied by ammonia and a water molecule. A mechanism is proposed for the second catalytic step, which includes a nucleophilic attack by the ammonia molecule on the intermediate.

Adenosine Triphosphate↗

Antihypertensive effects of angiotensin converting enzyme inhibition by lisinopril in post-transplant patients.

BACKGROUND: It is not known whether strict control of blood pressure (BP) in mild post-transplant hypertension gives any benefit. Our primary objective was to test the antihypertensive effects of lisinopril added to standard therapy on ambulatory BP (ABP) of post-transplant patients. The secondary objective was to monitor echocardiographic and hemodynamic end points. METHODS: Post-transplant patients with an abnormality of the 24-h ABP recording were recruited to this double-blind randomized prospective study that started 2 to 3 months after transplantation. Patients were then evaluated at 6, 12, 18, and 24 months after transplantation. RESULTS: Lisinopril decreased the clinic BP and ABP, the latter from 134/85 to 126/82 mm Hg at 6 months (P =.01 v placebo) and 121/79 mm Hg after 2 years (P =.03 v placebo). Fewer patients in the lisinopril group required added amlodipine to control the BP (P =.01). Data on left ventricular (LV) mass are difficult to interpret because by coincidence in this small study, the lisinopril group had lower initial values than placebo. However, in the lisinopril group mean LV mass decreased by 10% (P =.02) and mass index by 13% (P =.01), whereas placebo LV mass and index did not change. The LV end-diastolic diameter increased only in the placebo group (P =.008). There were no significant changes in any of the other secondary outcomes, including the cardiac index and systemic vascular resistance. CONCLUSIONS: Thus, in these post-transplant patients, stricter BP control to normal levels by the addition of lisinopril to existing therapy, reduced BP and modestly decreased LV mass without altering cardiac hemodynamic function.

Angiotensin-Converting Enzyme Inhibitors↗

Evaluation of peripheral blood CD4 and CD8 lymphocyte subsets, CD69 expression and histologic rejection grade as diagnostic markers for the presence of cardiac allograft rejection.

We investigated the dynamics of the CD4+ and CD8+ lymphocyte subsets, and the expression of activation markers in cardiac transplant recipients. We tested 132 peripheral blood samples from 62 cardiac transplant recipients using fluorescent staining and flow cytometry analysis. The results were correlated with histological rejection grade of concurrently taken biopsies, and 5-year survival of the recipients. A decrease in the total T lymphocyte subset, and in CD4+ lymphocytes was associated with higher rejection grade and lesser survival. An increase (5-11%) of double positive CD4+ CD8+ lymphocytes was observed; these were mostly CD4brightCD8dim. The CD4/CD8 ratio was significantly (P < 0.00) lower in the transplant recipients than in normal individuals. CD69 expression was higher than CD54 and CD154 expression on CD4 and CD8 lymphocytes of cardiac transplant recipients; correlation between these activation markers was excellent (P < 0.001). Fluorescent staining for CD69 was often of low intensity. Multiple regression for % CD8+ CD69+ cells and survival, and for % CD69+ T cells and rejection grade yielded a significant correlation (P < 0.050). Both % CD8+ CD69+ and % CD69+ T cells were significantly higher in samples with severe and moderate rejection grade (grades 3A, 3B and 4) than in samples which showed no, minimal or mild rejection (grades < or = 2); P-values were 0.052 and 0.003, respectively. Preliminary results indicated that false negative results could be contributed to increased immunosuppression. We conclude that CD69 expression on circulating CD4 and CD8 lymphocytes is a useful parameter for the diagnosis of moderate and severe rejection.

Antigens, CD↗

Novel strategy to stop cigarette smoking by surgical patients: pilot study in a preadmission clinic.

BACKGROUND: Evidence-based guidelines suggest that all services, wards and clinics within hospitals consider smoking status a vital sign and routinely provide cessation care. Despite this, such opportunities are currently under-utilized. The aim of the present pilot study was to determine the potential effectiveness, feasibility and acceptability of computer delivery of smoking cessation advice to surgical preadmission patients. METHODS: All smokers attending a non-cardiac surgical preadmission clinic at the John Hunter Hospital, New South Wales, completed a brief computerized smoking cessation intervention programme. Nine months following completion of the programme, patients completed a follow-up telephone interview that assessed their smoking status and the acceptability of the programme. RESULTS: At follow up, 22 of the 37 participants (60.0%) reported that they had stopped smoking prior to their surgery 9 months previously. Of the 37 participants at follow up, five reported that they were no longer smokers at that time, a cessation rate of 13.5%. Among those patients still smoking, a trend toward smoking fewer cigarettes was evident. Of the 56 smokers at baseline, all completed the computerized smoking cessation programme, with an average completion time of 21 min. A large majority of the smokers (80%) and non-smokers (88%) found that the provision of smoking cessation advice by the computer was appropriate and acceptable. Extrapolation of the results to a full year suggests a cost per quitter of $443. CONCLUSIONS: An interactive computerized smoking cessation programme is an acceptable and feasible method of routinely encouraging surgical preadmission clinic patients to stop or reduce their smoking. Further development and testing of the efficacy of this approach is required.

Admitting Department, Hospital↗

Structure and culture of schools of public health to support academic public health practice.

Schools of public health have been cautioned about producing graduates and research that were disconnected from public interest. Although institutions may implement a variety of strategies to rectify the situation, institutional structural and cultural barriers impede progress. Public health practice coordinators in accredited schools of public health were surveyed to describe the presence of structural and cultural barriers to academic public health practice using the Stevens model. Administrative leadership and faculty reward systems are described as critical to advance academic public health practice.

Education, Graduate↗