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L Olsen

Publications and source records attributed to L Olsen.

At least 19 recordsLinked to original sources

Intrinsic DNA distortion of the bacteriophage Mu momP1 promoter is a negative regulator of its transcription. A novel mode of regulation of toxic gene expression.

The momP1 promoter of the bacteriophage Mu mom operon is an example of a weak promoter. It contains a 19-base pair suboptimal spacer between the -35 (ACCACA) and -10 (TAGAAT) hexamers. Escherichia coli RNA polymerase is unable to bind to momP1 on its own. DNA distortion caused by the presence of a run of six T nucleotides overlapping the 5' end of the -10 element might prevent RNA polymerase from binding to momP1. To investigate the influence of the T(6) run on momP1 expression, defined substitution mutations were introduced by site-directed mutagenesis. In vitro probing experiments with copper phenanthroline ((OP)(2)Cu) and DNase I revealed distinct differences in cleavage patterns among the various mutants; in addition, compared with the wild type, the mutants showed an increase (variable) in momP1 promoter activity in vivo. Promoter strength analyses were in agreement with the ability of these mutants to form open complexes as well as to produce momP1-specific transcripts. No significant role is attributed to the overlapping and divergently organized promoter, momP2, in the expression of momP1 activity, as determined by promoter disruption analysis. These data support the view that an intrinsic DNA distortion in the spacer region of momP1 acts in cis as a negative element in mom operon transcription. This is a novel mechanism of regulation of toxic gene expression.

Bacteriophage mu↗

[Anti-reflux surgery is possible also in children with multiple disabilities. Good results after Nissen fundoplication in 10-years experience].

82 children with gastroesophageal reflux, 43 of whom were seriously neurologically impaired, were operated according to Nissen. A retrospective study compares the results, complications and recurrences between children with and children without neurological disability. There were no major differences between the groups; four of the neurologically impaired children and one without impairment had died from unrelated causes. In 62 children, 31 of whom were neurologically impaired, the operation was completely successful, 13 children (six of whom were neurologically impaired) had minor problems, two (both neurologically impaired) had major problems. The conclusion is that serious neurological impairment can not be considered a contraindication to antireflux surgery.

Adolescent↗

[Circumcision of boys--a child's right versus parents' right].

Male circumcision was practiced long before Abraham established a covenant with God to the effect that he should circumcize himself and all male members of his house. Thereafter it has become a potent religion-ethnic commandment also in the Islamic world, although it is not mentioned in the Koran. Several million boys are circumcised yearly in for instance traditional Africa and the USA (in the USA originally as prophylaxis against masturbation). In Sweden the yearly figure is some 3000 boys. A comprehensive review of the literature reveals that there are no or only marginal medical benefits of the operation, particularly in view of the fact that up to 10% suffer complications, and also that newborns both experience pain and will respond more strongly to new pain stimuli for years to come. There are two opposing interests--those related to the religious tradition and those related to the welfare of the child as expressed in the United Nations Convention on the Rights of the Child.

Child Welfare↗

Expression of leukaemia inhibitory factor during the development of the human enteric nervous system.

Leukaemia inhibitory factor (LIF) is a neuropoietic cytokine, which promotes the development of enteric neurons in vitro, particularly when administered together with neurotrophin-3 (NT-3). The purpose of this study was to map the LIF immunoreactivity in the human enteric nervous system in foetuses, children, adults, and in patients with Hirschsprung's disease. Normal bowel specimens were obtained at postmortem examination of 13 foetuses, at 13-31 weeks of gestation, and at surgery in five children and two adults. Bowel resected in seven patients with Hirschsprung's disease was also investigated. Immunohistochemical analysis was performed on material fixed in formalin and embedded in paraffin. The specimens were exposed to antibodies raised against LIF. The ABC-complex method was used to visualise binding of antibodies to the corresponding antigen. LIF immunoreactivity was disclosed in the myenteric and submucous ganglion cells at 13-31 weeks of gestation, in childhood cases, and adults. LIF-immunoreactive ganglion cells were absent in aganglionic bowel, where the ganglia in the intermuscular layer were replaced by hypertrophic nerve bundles. These morphological findings indicate that LIF may play a role in the development of the enteric nervous system.

Adult↗

From vision to reality: how to actualize the vision of discharging patients from a hospital, with an increased focus on prevention.

Experiences in creating dialogue possibilities to stimulate interdisciplinary and intersectoral collaboration in hospital discharge and prevention are presented. Time is often a major constraint that persuades decision-makers to avoid using qualitative methodologies in research and development. Quick results are demanded of today's health-care system, not allowing ideas to be implemented or visions owned by professionals. Action-orientated research is used and recommended, despite its time-demanding methodology. A multidisciplinary management team and the authors, over a 2-year period, worked with the development and implementation of 'Preventive Discharge' in a Danish hospital clinic. The empirical starting point, developmental processes, piloting and implementation of the project are described. Earlier research from a literature review on discharge is referenced. The results show that while there are many barriers to dialogue between professions and between organizational levels, it is possible to frame such opportunities and improve interdisciplinary and intersectoral collaboration for health. External supervision may be an effective tool for stimulating dialogue. The testing phase afforded a valuable lesson when pilot-site collaborators, initially not involved in the development of the process tools, reformulated the project to suit their cultural climate while maintaining the project's original aims. Finally, a discussion is presented on actualizing the vision for 'Preventive Discharge'.

Aged↗

Induction of micronuclei in V79 cells by fractions of roofing asphalt fume condensate.

More than 50,000 workers in the United States are exposed to roofing asphalt fumes that may pose genotoxic and potential carcinogenic hazards. The Type III roofing asphalt is most frequently used in roof-application. Results of our previous studies showed that fume condensates of Type III roofing asphalts induced micronuclei (MN) in vitro in cultured V79 cells and DNA adduct formation in vivo in rat lung cells. In this study, the genotoxicity of whole fume condensates (WFC) of Type III roofing asphalt and its five chemical fractions (A, B, C, D and E) was determined by the micronucleus assay using V79 cells. Linear regressions were determined for the dose response of MN frequencies and percent of binucleated and multinucleated cells (MTC) following the treatment. Results showed that the numbers of micronucleated cells in cultures treated with Type III roofing asphalt WFC and its fractions B, C, D and E were significantly higher than that in the control culture, and that the slopes of the linear regression line for fractions B and C were greater than those for the WFC and fractions D and E. A clear dose response of binucleated cells was also induced by the WFC and fractions B and C. These findings indicate that: (1) WFC and all fractions, except fraction A, induced MN formation in cultured V79 cells; (2) fractions B and C possess the highest genotoxic activity; (3) the roofing asphalt WFC contains chemicals or chemical classes that induce not only chromosomal aberrations but also binucleation in V79 cells.

Animals↗

Pressure-flow studies: short-time repeatability.

The within and between examination variation in selected test parameters and test results in repeated pressure-flow studies was determined in a prospective study of consecutive pressure-flow examinations in 22 patients. The patients were pressure-flow tested twice within a month. Furthermore, it was evaluated whether there was a systematic change in the measured parameters during retesting. By using the Abrams-Griffiths nomogram, patients were classified as obstructed, equivocal, or unobstructed. Within and between examination variations in classification were evaluated. We found a systematic variation in P(det.Qmax) during testing, which in the absence of statistically significant systematic variations in P(det.Close) and Qmax, indicates a physiological effect of repeated pressure-flow studies, resulting in a less-obstructed second voiding. Supporting this, we found that all patients who changed group of classification of bladder outlet obstruction in the first examination shifted to a group of less obstruction, as did 66% of the patients who changed group of classification of bladder outlet obstruction in the second examination. Still, 80, respectively 85%, of the patients remained in the same group of classification of bladder outlet obstruction during retesting in the first and second examinations, respectively. Classifying the degree of bladder outlet obstruction by Qmax, P(det.Qmax), and P(det.Close) 85% of the patients reproduced their test results accurately in both examinations and taking only the first voiding in both examinations into account 95% reproduced their test results.

Aged↗

Mathematical modelling of anisotropy in fibrous connective tissue.

We present two modelling frameworks for studying dynamic anistropy in connective tissue, motivated by the problem of fibre alignment in wound healing. The first model is a system of partial differential equations operating on a macroscopic scale. We show that a model consisting of a single extracellular matrix material aligned by fibroblasts via flux and stress exhibits behaviour that is incompatible with experimental observations. We extend the model to two matrix types and show that the results of this extended model are robust and consistent with experiment. The second model represents cells as discrete objects in a continuum of ECM. We show that this model predicts patterns of alignment on macroscopic length scales that are lost in a continuum model of the cell population.

Anisotropy↗

Safe biotechnology 9: values in risk assessment for the environmental application of microorganisms. The Safety in Biotechnology Working Party of the European Federation of Biotechnology.

Risk assessment for the deliberate release of microorganisms into the environment is traditionally carried out on a case-by-case basis. In a similar approach to that used when assessing human pathogenicity, we propose an alternative approach by introducing risk classes to facilitate or complement this type of risk assessment. These consider several sets of scenarios that address the different values that need to be protected. Examples of this approach include risk-class definitions for soil fertility and biodiversity.

Bacteria↗

Accessory wandering spleen associated with short pancreas. A pediatric case report.

We present an extremely rare case of a 5-year-old girl with short pancreas associated with three accessory spleens, one of which was a large wandering spleen. The diagnosis was established by US and CT. A large accessory wandering spleen is considered to be at risk of torsion and infarction as well as susceptible to abdominal trauma. The authors discuss the difficulty of establishing the diagnosis and underline the importance of US and CT as pre-operative diagnostic tools.

Abdominal Pain↗

Interstitial cells of Cajal in the human fetal small bowel as shown by c-kit immunohistochemistry.

BACKGROUND: Interstitial cells of Cajal (ICCs) express the tyrosine kinase receptor c-kit, which is required for their development and spontaneous pacemaker activity in the bowel. From murine models it has been proposed that ICCs do not develop until after birth, but more recent findings indicate that c-kit is expressed early in the embryonic period. The temporal development of ICCs in the human gut remains unknown. AIM: To investigate ICCs in the human fetal small bowel using c-kit immunohistochemistry. SUBJECTS: Small bowel specimens were obtained at post mortem examination of 16 fetuses and nine neonates, eight of whom were premature, born at gestational ages of 13 to 41 weeks, without gastrointestinal disorders. METHODS: Immunohistochemical analysis was performed on material fixed in formalin and embedded in paraffin. The specimens were exposed to antibodies raised against c-kit (an ICC marker) and neurone specific enolase (a general neuronal marker). The ABC complex method was used to visualise binding of antibodies to the corresponding antigens. RESULTS: c-kit immunoreactive cells were visualised from 13 weeks of gestation. The immunoreactivity was mainly localised in association with the myenteric plexus. From about 17-18 weeks of gestation, the ICCs formed a layer along the myenteric plexus, whereas this layer appeared to be disrupted at 13-16 weeks of gestation. CONCLUSIONS ICCs are c-kit immunoreactive at least from a gestational age of 13 weeks in the human fetal small intestine. From 17-18 weeks of gestation until birth, they form a continuous layer around the myenteric ganglia.

Embryonic and Fetal Development↗

Attention-deficit hyperactivity disorder in children and youth: a quantitative systematic review of the efficacy of different management strategies.

OBJECTIVE: To obtain estimates of the relative efficacy of 3 main treatment strategies for attention-deficit hyperactivity disorder (ADHD) in children and youth (age < 18 years). METHODS DESIGN: quantitative systematic review of randomized trials. SUBJECTS: 999 patients with ADHD from 26 randomized trials. INTERVENTIONS: medications alone, behavioural interventions alone, and a combination of these 2 modalities. MAIN OUTCOME MEASURE: differences in scores between treatment groups on commonly used teacher- and parent-completed behaviour rating scales. RESULTS: Medication-only therapy was efficacious in ADHD. Behavioural therapies used alone appeared not to be efficacious in ADHD. Combination therapy was more efficacious than placebo or no treatment for parent but not teacher ratings, not more efficacious than drug therapy alone, and more efficacious than behavioural treatments alone based on parent but not teacher ratings. CONCLUSION: Though stimulant medications were found to be an effective treatment strategy for ADHD in children and youth, it proved difficult to assess the relative benefits of behavioural interventions alone and combined medication and behavioural therapy because of the paucity of treatment studies other than medication-only treatment studies and heterogeneity of various kinds that exist in relation to ADHD studies and treatments.

Adolescent↗

Expression of bcl-2 in enteric neurons in normal human bowel and Hirschsprung disease.

OBJECTIVE: The bcl-2 protein has the functional role of blocking apoptosis, ie, programmed cell death. This protein is widely expressed in the developing central and peripheral nervous systems. The purpose of this study was to map bcl-2 expression in the human enteric nervous system, as this has not previously been done. METHODS: Rectal specimens were obtained at autopsy of 13 fetuses at 13 to 31 weeks of gestation. Normal colon was also obtained from 5 children and 2 adults, and, in addition, ganglionic and aganglionic bowel resected in 11 patients with Hirschsprung disease was examined. Specimens were fixed in formalin, embedded in paraffin, and analyzed with immunohistochemical methods, using antibodies raised against bcl-2 and neuron-specific enolase (NSE). RESULTS: The bcl-2 protein was expressed in myenteric and submucous ganglion cells in fetuses, children, and adults. Nerve fibers of the enteric plexuses that were bcl-2 immunoreactive were few compared with the number of NSE-immunoreactive nerve fibers. In aganglionic bowel no bcl-2-or NSE-immunoreactive ganglion cells were revealed. Results of NSE immunohistochemistry showed clearly stained hypertrophic nerve bundles, known to be of extrinsic origin, which were only weakly bcl-2 immunoreactive. CONCLUSION: Expression of bcl-2 in enteric ganglion cells of the myenteric and submucous plexuses is displayed in the fetus and during childhood and is also retained in adult bowel. Immunohistochemical analysis of bcl-2 provides a good marker for identification of ganglion cells in Hirschsprung disease and may also be valuable for the diagnosis of disorders characterized by hypoganglionosis or hyperganglionosis.

Aged↗

Differential expression of inducible nitric oxide synthase in septic shock.

During cardiopulmonary bypass (CPB), the septic patient has markedly decreased peripheral vascular resistance as a consequence of endotoxin release from microorganisms. This decrease in peripheral vascular resistance is the result of endotoxin-induced nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). iNOS and eNOS are responsible for the synthesis of NO because of various stimuli, including the bacterial endotoxin, lipopolysaccharide (LPS). We tested the hypothesis that a differential expression of iNOS among human endothelial cells and murine macrophage is dependent upon exposure to endotoxin and various pro-inflammatory cytokines. Using a human endothelial cell line, ECV-304 and murine macrophage cell line, RAW 264.7, we quantified the expression of iNOS with specific FITC-conjugated antibodies using fluorescence activated cell sorter (FACS) and NO production with a Bioxytech nitric oxide spectrophotometric assay. This in vitro septic model utilized LPS supported with species-specific interferon-gamma, interleukin-1 beta, and tumor necrosis factor-alpha. The cell type were stimulated for 8 hours with combinations of the cytokines mentioned. The FACS data demonstrated a significant stimulus-dependent increase in iNOS expression among the macrophage groups; however, the stimulated endothelial cells showed no significant change in iNOS expression. The nitric oxide production data demonstrated significant increases in NO production among macrophage stimulated groups; whereas, endothelial stimulated groups exhibit no significant change. We conclude that NO secreted during septic shock is the result of activated macrophage, not the endothelium. The clinical relevance is that the more severe the infectious process, the lower the PVR may be during CPB because of increased NO production from activated macrophage.

Animals↗