Ivory tower derision.
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Attitude of Health Personnel↗
Biomedical subjects
N Cole
Publications and source records attributed to N Cole.
Organisational infrastructures to promote evidence based nursing practice.
BACKGROUND: The purpose of this systematic review is to determine to what extent organisational infrastructures are effective in promoting the implementation of high quality research evidence on the effectiveness of nursing interventions. OBJECTIVES: To identify and summarize rigorous evaluations of organisational infrastructure developments aimed at promoting evidence based nursing practice. SEARCH STRATEGY: We searched: The Cochrane Library, MEDLINE, EMBASE, CINAHL, SIGLE, HEALTHLINE, National Research Register, Nuffield Database of Health Outcomes, NIH Databases up to August 2002. We hand searched the Journal of Advanced Nursing, Applied Nursing Research and Journal of Nursing Administration (to 1999), and checked the reference lists of articles obtained. We contacted experts in the field and relevant Internet groups. SELECTION CRITERIA: Randomized controlled trials, controlled clinical trials and interrupted times series studies of an entire or identified component of an organisational infrastructure development aimed at promoting effective nursing interventions. The participants were health care organisations comprising nurses, midwives and health visitors in hospital and community settings. DATA COLLECTION AND ANALYSIS: All identified papers were screened independently for relevance, design and outcome by two reviewers. MAIN RESULTS: No studies were sufficiently rigorous to be included in this systematic review. Seven case study evaluations were identified but excluded from the review because of poor design and lack of controls. REVIEWER'S CONCLUSIONS: 1. There are no clear implications for practice.2. Several conceptual models on organisational processes to promote evidence based practice have been described in published papers, and a number of organisational infrastructural interventions have been described in published papers. None have been evaluated properly. The next step in this field should be to conduct well planned evaluations of well planned interventions. 3. Interrupted and Complex Interrupted Times Series (ITS and CITS) designs should be adopted as a useful alternative to randomized controlled trials where such trials would be impractical. The health service cost of any infrastructure developments should be assessed in any evaluation. If possible, patient outcomes should be measured directly.
Efficiency, Organizational↗
Treatment of carious deciduous teeth.
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Child↗
The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).
Amino Acid Sequence↗
Effects of exogenous interleukin-6 during Pseudomonas aeruginosa corneal infection.
Lack of interleukin-6 (IL-6) during Pseudomonas aeruginosa corneal infection leads to more severe disease with changes in neutrophil recruitment. Exogenous IL-6 leads to increased efficiency of neutrophil recruitment and reduced bacterial loads in corneal infection in both IL-6 gene knockout and wild-type mice. This may be mediated by IL-6 increasing the production of corneal macrophage inflammatory protein 2 and intercellular cell adhesion molecule 1. We conclude that effective recruitment of neutrophils into the cornea is dependent on the production of IL-6 and that early augmentation of IL-6 may be protective in corneal infection.
Animals↗
Multiple transcripts of the human Cu,Zn superoxide dismutase gene.
We have identified five alternatively spliced transcripts of the gene for human Cu,Zn superoxide dismutase (SOD1), a causative gene for autosomal dominant amyotrophic lateral sclerosis (ALS). The splice variants of wild-type or mutant SOD1 were expressed in a tissue-specific manner; therefore, their expression may be regulated to modify SOD1 function. In addition, the expression in the brain implies that variants may play a role in the nervous system, the region involved in ALS. Immunoblot study of HeLa cells transfected with two variants encoding C-terminal truncated proteins did not show the proteins of expected size. However, this observation is consistent with the previous study of C-terminal truncated mutant proteins that cause ALS, suggesting that both variant and mutant proteins may share certain properties, such as instability or insolubility in the cytosol. These findings suggest that the splice variants may contribute to a physiological function of SOD1 or to a pathological mechanism in ALS.
Alternative Splicing↗
KC production in the cornea in response to Pseudomonas aeruginosa challenge.
Pseudomonas aeruginosa can cause ulcerative bacterial keratitis. A feature of keratitis is the rapid infiltration of the avascular corneal stroma by neutrophils. KC is a potent neutrophil chemokine. The present study used a mouse model of ocular infection to assess the relationship between KC and inflammation in the cornea in response to challenge with a strain of P. aeruginosa causing keratitis. Low levels of KC mRNA and protein were detected by in situ hybridization and ELISA, respectively, in unchallenged corneas. Dramatically increased numbers of KC mRNA+ cells were present in P. aeruginosa strain 6294-challenged corneas. Expression of KC mRNA was found to be up-regulated in the corneal epithelium in response to wounding alone. The KC mRNA+ cells were located in the epithelium and corresponding to infiltrating neutrophils cells in the stroma. Quantification of KC protein at different time points showed peak levels at 8 h of bacterial challenge. These results suggest that KC may be involved with the regulation of leucocyte infiltration early during bacterial keratitis.
Animals↗
Differential interleukin-6 mRNA expression in Nippostrongylus brasiliensis infection of susceptible and resistant strains of mice.
Intestinal parasitic infection is still a major problem in humans and animals, yet host immunity against gut parasitic infection remains partially understood. Eosinophilia and mastocytosis are features of such infection that have been shown to be genetically controlled. The expression of IL-6 is detected in eosinophils, mast cells and neutrophils and may be responsible for the regulation of leucocytes at infective sites. The relationships between IL-6 expression, eosinophilia, mastocytosis and host immunity remain unclear. In the present report, a close correlation between IL-6 mRNA+ cells, eosinophilia, mastocytosis and worm expulsion is demonstrated, which may indicate a role for IL-6 in regulation of host immunity against intestinal parasite infection.
Animals↗
Protein microanalysis of animal tears.
Sub-microlitre volumes of normal koala, mouse, dog, rat and cat tears were fractionated using size exclusion-high performance liquid chromatography (SE - HPLC), giving reproducible profiles which were different for each species. Microlitre volumes of tears were also fractionated using sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS - PAGE), resulting in good separation of individual tear proteins with a species specific distribution. Tears from koalas with conjunctivitis and mice with keratitis were similarly examined and showed mostly quantitative changes. These simple, rapid techniques gave reproducible results and, in contrast to conventional separation techniques, used easily obtainable volumes (as little as 0.75 microl) of tears. Their expansion could allow isola tion, identification and quantitation of individual tear components, enabling effective investigation of changes occurring in disease.
Animals↗
TNF-alpha production in the cornea in response to Pseudomonas aeruginosa challenge.
Pseudomonas aeruginosa can cause ulcerative bacterial keratitis or contact lens-induced acute red eye (CLARE) in humans. The present study used a mouse model of ocular infection and inflammation to examine the relationship between TNF-alpha and inflammation in the cornea in response to challenge with either a strain of P. aeruginosa causing keratitis or a CLARE strain. Constitutive TNF-alpha mRNA was detected in the epithelium, mainly towards the periphery. After infection with the keratitis-inducing strain (6294), TNF-alpha expression was elevated four-fold by 24 h post-challenge. No detectable induction of TNF-alpha mRNA was seen with CLARE strain (Paer1) challenge at any time point. The TNF-alpha protein production detected by ELISA showed a corresponding pattern to the mRNA expression, which also correlated with pathological changes. These results suggest that invasive strains of P. aeruginosa create greater pathological changes as a result of elevated TNF-alpha production, which contributes to inflammation during keratitis in vivo.
Animals↗
Genetic disorders of motor neurons.
Disorders of the motor neuron are etiologically and clinically heterogeneous and cause serious disability and death. Whereas mendelian inheritance can be demonstrated in a subset of these disorders, the genetic contribution to the sporadic forms of motor neuron degeneration are not well understood. In families with spinal muscular atrophy, Kennedy disease and amyotrophic lateral sclerosis, genetic linkage analysis and positional cloning have proven to be extremely productive. The genetics of these neurodegenerative disorders are reviewed.
Amyotrophic Lateral Sclerosis↗
Van Gogh and lithium. Creativity and bipolar disorder: perspective of a lawyer/parliamentarian.
Neil Cole has been the State Member for Melbourne since 1988 and was a Melbourne City Councillor for 3 years. He was the first Member of Parliament in Australia to confront the stigma of mental illness by publicly acknowledging his manic depression. Prior to entering parliament he was a Community Lawyer at Flemington Community Legal Service for 7 years. Neil was National Convenor of the Nuclear Free Zone Secretariat (1986-88), Chairperson Joint Parliamentary Economic and Budget Review Committee (1991-92) and Shadow Attorney General from 1992 to 1995. He is Deputy Chair of the Joint Parliamentary Law Reform Committee of the Victorian Parliament. Neil has written three plays with 'Alive at Williamstown Pier' being his first. He is currently employed as a consultant to the Mental Health Research Institute at Royal Park Melbourne.
Affect↗
Expression of interleukin-6 in the cornea in response to infection with different strains of Pseudomonas aeruginosa.
Strains of Pseudomonas aeruginosa causing keratitis can be either cytotoxic (6206) or invasive (6294), while a strain (Paer1) causing contact lens-induced acute red eye has been shown to be neither. In situ hybridization was used to examine the location and identity of cells expressing interleukin-6 (IL-6) mRNA in the murine cornea and changes in expression in response to infection with different strains of P. aeruginosa. The number of IL-6-positive cells was determined by image analysis. IL-6 protein levels were measured by an enzyme-linked immunosorbent assay. BALB/c mice were challenged by use of the wounded-cornea model with P. aeruginosa 6294, 6206, or Paer1 (2 x 10(6) CFU). At time intervals up to 24 h, postchallenge corneal tissue was probed for IL-6 mRNA. IL-6 mRNA expression was rapidly elevated in the epithelium in response to strains 6294 and 6206. At the conclusion of the experiments, infiltrating inflammatory cells also stained positively for IL-6 mRNA. In contrast, corneas challenged with strain Paer1 showed significant upregulation of IL-6 mRNA only at 4 h postchallenge. Three distinct patterns of IL-6 mRNA expression in the mouse cornea occur in response to these three ocular isolates of P. aeruginosa. The data obtained for mRNA expression in the cornea for all three strains of P. aeruginosa correlated well with IL-6 protein analysis of whole-eye homogenates. Differences in the cytokine responses to these strains correlate with differences in the pathology associated with each strain and may offer an opportunity to develop strategies for the improved management of ocular inflammation.
Animals↗
Unravelling Golgi membrane traffic with green fluorescent protein chimeras.
An important new tool for investigating how the Golgi receives cargo and maintains its integrity in the face of ongoing secretory traffic has emerged with the advent of green fluorescent protein (GFP) chimeras. GFP chimeras, which can be visualized in the unperturbed environment of a living cell, are being used in a wide variety of applications to study Golgi dynamics. These include time-lapse imaging, double-label and photobleach experiments. These studies are helping to clarify the steps involved in the formation, translocation and fate of transport intermediates associated with the Golgi complex, including the roles of cytoskeletal elements. They are also providing insights into mechanisms of protein retention and localization within Golgi membranes.
Animals↗
Embryonic temperature modulates muscle growth characteristics in larval and juvenile herring
The influence of embryonic and larval temperature regime on muscle growth was investigated in Atlantic herring (Clupea harengus L.). Eggs of spring-spawning Clyde herring were incubated at 5 degrees C, 8 degrees C or 12 degrees C until hatching and then reared until after metamorphosis at rising temperatures to simulate a seasonal warming. Metamorphosis to the juvenile stage was complete at 37 mm total length (TL), after an estimated 177 days as a larva at 5 degrees C, 117 days at 8 degrees C and 101 days at 12 degrees C. Growth rate and the development of median fins were retarded in relation to body length at 5 degrees C compared with 8 degrees C and 12 degrees C. Between hatching (at 8-9 mm TL) and 16 mm TL, there was a threefold increase in total muscle cross-sectional area, largely due to the hypertrophy of the embryonic red and white muscle fibres. The recruitment of additional white muscle fibres started at approximately 15 mm TL at all temperatures, and by 37 mm was estimated to be 66 fibres day-1 at 5 degrees C and 103 fibres day-1 at 8 degrees C and 12 degrees C. Peptide mapping studies revealed a change in myosin heavy chain composition in white muscle fibres between 20 and 25 mm TL. Embryonic red muscle fibres expressed fast myosin light chains until 24-28 mm TL at 5 degrees C and 22 mm TL at 12 degrees C, and new red fibres were added at the horizontal septum starting at the same body lengths. Following metamorphosis, the total cross-sectional area of muscle was similar at different temperatures, although the number of red and white fibres per myotome was significantly greater at the warmest than at the coldest regime. For example, the mean number of white muscle fibres per myotome in 50 mm TL juveniles was calculated to be 23.4 % higher at 12 degrees C (12 065) than at 5 degrees C (9775). In other experiments, spring-spawning (Clyde) and autumn-spawning (Manx) herring were reared at different temperatures until first feeding and then transferred to ambient seawater temperature and fed ad libitum for constant periods. These experiments showed that, for both stocks, the temperature of embryonic development influenced the subsequent rate of muscle fibre recruitment and hypertrophy as well as the density of muscle nuclei. Labelling experiments with 5'-bromo-2-deoxyuridine showed that both the hypertrophy and recruitment of muscle fibres involved a rapidly proliferating population of myogenic precursor cells. The cellular mechanisms underlying the environmental modulation of muscle growth phenotype are discussed.
Journal Article↗
Scaling of intrinsic contractile properties and myofibrillar protein composition of fast muscle in the fish myoxocephalus scorpius L
Contractile properties were determined for fast muscle fibres from short-horn sculpin (Myoxocephalus scorpius L.) ranging from 5 to 35 cm total body length (L) and from 2.0 to 758 g body mass. Maximum unloaded shortening velocity (V0) decreased with increasing body size, scaling as 19.5L-0.34, and isometric twitch activation and tetanus relaxation times became longer, scaling as 12.0L0.31 and 19. 5L0.42 respectively. Myofibrillar Mg2+/Ca2+-ATPase activity scaled as 2.51L-0.28. In order to investigate the mechanisms underlying the scaling of contractile properties, myofibrillar protein composition and I filament lengths were determined. One-dimensional SDS-PAGE and two-dimensional isoelectric focusing/non-equilibrium isoelectric focusing-PAGE revealed no differences in the myofibrillar protein isoforms of myosin light chains, actin, tropomyosin, troponin-T and troponin-C in fish of differing body size. Peptide maps of purified myosin heavy chains digested with eight different proteolytic enzymes were also similar in all fish examined. Three isoforms of troponin-I were present in fish less than 20 cm in total length with relative molecular masses of 17 (TnIf3), 22 (TnIf2) and 23 (TnIf1). The ratio of TnI isoforms varied with body length, and only TnIf3 was present in fish greater than 28 cm total length. The length of I filaments was independent of body length. Thus, although the expression of TnI isoforms changes during growth, the underlying mechanism responsible for increased shortening velocity with decreased body size remains unknown.
Journal Article↗
Different strains of Pseudomonas aeruginosa isolated from ocular infections or inflammation display distinct corneal pathologies in an animal model.
PURPOSE: The present investigation sought to define the responses of mouse eyes to challenge with three different strains of P. aeruginosa isolated from human corneas or contact lenses: two different strains produced an ulcerative keratitis, and one strain produced contact lens-induced acute red eye (CLARE). METHODS: The corneas of BALB/c mice were inoculated with three different strains of P aeruginosa. The strains were allowed to interact with the corneas for up to 24 h. In addition, strain Paerl, isolated from CLARE, was subjected to in vitro assays to measure its ability to invade corneal epithelial cells, or to produce cytotoxicity in these cells. Both these assays used cultured rabbit corneal epithelial cells. RESULTS: Both MK isolates were able to infect the corneas of mice, but the CLARE isolate was non-infective. The predominant response to infection with the cytotoxic strain was severe corneal edema and infiltration of the corneal stroma with polymorphonuclear leukocytes (PMNs). The predominant response with the invasive MK isolate was corneal ulceration and infiltration with PMNs. The CLARE strain produced only low levels of PMN infiltration. In in vitro assays the CLARE strain was non-invasive and non-cytotoxic. CONCLUSIONS: This study has identified that P. aeruginosa produces at least three different types of corneal pathology and that not all strains are able to infect mouse corneas.
Animals↗
Golgi tubule traffic and the effects of brefeldin A visualized in living cells.
The Golgi complex is a dynamic organelle engaged in both secretory and retrograde membrane traffic. Here, we use green fluorescent protein-Golgi protein chimeras to study Golgi morphology in vivo. In untreated cells, membrane tubules were a ubiquitous, prominent feature of the Golgi complex, serving both to interconnect adjacent Golgi elements and to carry membrane outward along microtubules after detaching from stable Golgi structures. Brefeldin A treatment, which reversibly disassembles the Golgi complex, accentuated tubule formation without tubule detachment. A tubule network extending throughout the cytoplasm was quickly generated and persisted for 5-10 min until rapidly emptying Golgi contents into the ER within 15-30 s. Both lipid and protein emptied from the Golgi at similar rapid rates, leaving no Golgi structure behind, indicating that Golgi membranes do not simply mix but are absorbed into the ER in BFA-treated cells. The directionality of redistribution implied Golgi membranes are at a higher free energy state than ER membranes. Analysis of its kinetics suggested a mechanism that is analogous to wetting or adsorptive phenomena in which a tension-driven membrane flow supplements diffusive transfer of Golgi membrane into the ER. Such nonselective, flow-assisted transport of Golgi membranes into ER suggests that mechanisms that regulate retrograde tubule formation and detachment from the Golgi complex are integral to the existence and maintenance of this organelle.
Animals↗