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Biomedical subjects

L Persson

Publications and source records attributed to L Persson.

At least 19 recordsLinked to original sources
PubMed2001

Importance of the 3' untranslated region of ornithine decarboxylase mRNA in the translational regulation of the enzyme.

Translational regulation of ornithine decarboxylase (ODC), which catalyses the first step in the biosynthesis of polyamines, appears to be an important mechanism in the strong feedback control as well as in the hypotonic induction of the enzyme. However, the exact mechanisms are not yet understood. The ODC mRNA has long 5' and 3' untranslated regions (UTRs) which may be involved in the translational control of the enzyme. In the present study we have used a series of stable transfectants of Chinese Hamster ovary cells expressing ODC mRNAs with various truncations in the 5' and 3' UTRs to investigate the importance of these regions. It is demonstrated that neither the 5' UTR nor the 3' UTR appears to be involved in the polyamine-mediated feedback control of ODC synthesis. The hypotonic induction of ODC, on the other hand, was shown to be highly dependent on the presence of the 3' UTR, but not on the 5' UTR, of ODC mRNA. Cells expressing ODC mRNAs lacking the 3' UTR showed no, or only a very slight, induction of ODC whether the 5' UTR was present or not, whereas the cell lines expressing ODC mRNAs containing the 3' UTR (with or without the 5' UTR) markedly induced ODC after a hypotonic shock. The present finding of a role for the ODC mRNA 3' UTR in the hypotonic induction of ODC is the first demonstration of a specific effect of the 3' UTR in the regulation of ODC.

3' Untranslated Regions↗
PubMed2001

Intensive care management of head-injured patients in Europe: a survey from the European brain injury consortium.

OBJECTIVES: (a) to describe current practice in the monitoring and treatment of moderate and severe head injuries in Europe; (b) to report on intracranial pressure and cerebral perfusion pressure monitoring, occurrence of measured and reported intracranial hypertension, and complications related to this monitoring; (c) to investigate the relationship between the severity of injury, the frequency of monitoring and management, and outcome. METHODS: A three-page questionnaire comprising 60 items of information has been compiled by 67 centres in 12 European countries. Information was collected prospectively regarding all severe and moderate head injuries in adults (> 16 years) admitted to neurosurgery within 24 h of injury. A total of 1005 adult head injury cases were enrolled in the study from 1 February 1995 to 30 April 1995. The Glasgow Outcome Scale was administered at 6 months. RESULTS: Early surgery was performed in 346 cases (35%); arterial pressure was monitored invasively in 631 (68%), ICP in 346 (37%), and jugular bulb saturation in 173 (18%). Artificial ventilation was provided to 736 patients (78%). Intracranial hypertension was noted in 55% of patients in whom ICP was recorded, while it was suspected in only 12% of cases without ICP measurement. There were great differences in the use of ventilation and CPP monitoring among the centres. Mortality at 6 months was 31%. There was an association between an increased frequency of monitoring and intervention and an increased severity of injury; correspondingly, patients who more frequently underwent monitoring and ventilation had a less favourable outcome. CONCLUSIONS: In Europe there are great differences between centres in the frequency of CPP monitoring and ventilatory support applied to head-injured patients. ICP measurement disclosed a high rate of intracranial hypertension, which was not suspected in patients evaluated on a clinical basis alone. ICP monitoring was associated with a low rate of complications. Cases with severe neurological impairment, and with the worse outcome, were treated and monitored more intensively.

Adult↗
PubMed2001

An evaluation of the ethical principles of the ICRP's radiation protection standards for workers.

After reviewing international recommendations and national standards for occupational radiation exposures, the article summarizes the major ethical theories so as to analyze which theories various ICRP principles presuppose. It also shows how proponents of each ethical theory would support or criticize various radiation principles and practices. Finally the article discusses four ethical issues crucial to the debate over workplace standards for radiation: (1) how to respond to the uncertainty over effects of low-dose exposures; (2) the conditions under which worker consent legitimates higher exposures; (3) whether there ought to be a double standard for worker, vs. public, exposures; and (4) whether ethics allows money-for-health tradeoffs in radiation protection. The article concludes with several recommendations about how to make occupational exposure to radiation more ethically defensible.

Dose-Response Relationship, Radiation↗
PubMed2001

Increase of interstitial glycerol reflects the degree of ischaemic brain damage: a PET and microdialysis study in a middle cerebral artery occlusion-reperfusion primate model.

OBJECTIVE: To evaluate interstitial glycerol as a marker of ischaemia by studying the changes in glycerol in direct relation to changes in regional cerebral metabolic rate of oxygen (CMRO(2)), the lactate/pyruvate ratio (LP ratio), and glutamate. METHODS: Transorbital 2 hour middle cerebral artery occlusion (MCAO) was performed in eight monkeys, which were studied with continuous microdialysis for 24 hours. Interstitial fluids were collected by microdialysis and analysed for glycerol, lactate, pyruvate, and glutamate with an enzymatic assay and high performance liquid chromatography. Sequential PET studies of cerebral blood flow (CBF), CMRO(2), oxygen extraction ratio (OER), and cerebral blood volume (CBV) were performed. The microdialysis probe regions were classified as severe ischaemia or penumbra, depending on whether the mean CMRO(2) side to side ratio was below or above 60%, respectively. RESULTS: A nine-fold, sustained increase in glycerol was registered after MCAO in severe ischaemia regions. In penumbra regions, the increase in glycerol was five-fold, but the glycerol concentration returned to baseline within 8 hours of clip removal. The difference between severe ischaemia and penumbra glycerol values was statistically significant. As expected from previous studies, the interstitial LP ratio and glutamate increased markedly in severe ischaemia, with a less pronounced change in penumbra regions. There was a time lag between the biochemical changes in severe ischaemia regions, with the LP ratio preceding glutamate, followed by glycerol. CONCLUSIONS: A marked, sustained increase in interstitial glycerol is indicative of severe ischaemia in this stroke model. A transient, diminutive increase in interstitial glycerol may reflect a penumbra situation. Interstitial glycerol in combination with other biochemical markers such as the LP ratio and glutamate may be useful for clinical monitoring of the ischaemic brain, reflecting a sequence of secondary pathophysiological events.

Animals↗
PubMed2001

Middle cerebral artery occlusion and reperfusion in primates monitored by microdialysis and sequential positron emission tomography.

BACKGROUND AND PURPOSE: In a previous investigation concerning the hemodynamic and metabolic changes over time displayed by sequential positron emission tomography (PET) in a middle cerebral artery (MCA) occlusion/reperfusion primate model, a metabolic threshold for irreversible ischemia could be identified (reduction of metabolic rate of oxygen [CMRO(2)] to approximately 60% of the contralateral hemisphere). To evaluate the potential of microdialysis (MD) as an instrument for chemical brain monitoring, the aim of this subsequent study was to relate the chemical changes in MD levels directly to the regional metabolic status (CMRO(2) above or below the metabolic threshold) and the occurrence of reperfusion, as assessed by PET. METHODS: Continuous MD (2 probes in each brain) and sequential PET measurements were performed during MCA occlusion (2 hours) and 18 hours (mean) of reperfusion in 8 monkeys (Macaca mulatta). Energy-related metabolites (lactate, pyruvate, and hypoxanthine) and glutamate were analyzed. The MD probe regions were divided into 3 categories on the basis of whether CMRO(2) was below or above 60% of the contralateral region (metabolic threshold level) during MCA occlusion and whether reperfusion was obtained: severe ischemia with reperfusion (n=4), severe ischemia without reperfusion (n=4), and penumbra with reperfusion (n=5). RESULTS: The lactate/pyruvate ratio, hypoxanthine, and glutamate showed similar patterns. MD probe regions with severe ischemia and reperfusion and probe regions with severe ischemia and no reperfusion displayed high and broad peaks, respectively, during MCA occlusion, and the levels almost never decreased to baseline. Penumbra MD probe regions displayed only slight transient increases during MCA occlusion and returned to baseline. CONCLUSIONS: This experimental study of focal ischemia showed that the extracellular changes of energy-related metabolites and glutamate differed depending on the ischemic state of the brain during MCA occlusion and depending on whether reperfusion occurred. If MD proves to be beneficial in clinical practice, it appears important to observe relative changes over time.

Animals↗
PubMed2001

Tobacco smoking and neutrophil activity in patients with periodontal disease.

BACKGROUND: Tobacco smoking has considerable negative effects on periodontal health. The mechanisms behind these effects are incompletely understood but may be related to the host response. The aim of the present study was to investigate the influence of tobacco smoking on the gingival crevicular fluid (GCF) levels of elastase, lactoferrin (LF), alpha-1-antitrypsin (alpha-1-AT), and alpha-2-macroglobulin (alpha-2-MG) under periodontally diseased conditions. METHODS: The study population included 15 smokers (5 women and 10 men) aged 34 to 69 years and 17 non-smokers (5 women and 12 men) aged 31 to 81 years. Clinical registration of gingival index (GI), plaque index (PI), probing depth, as well as sampling of GCF were made at 3 sites with severe lesions and 3 sites with moderate lesions in each individual. The elastase activity was measured with a chromogenic low molecular substrate and the LF, alpha-1-AT, and alpha-2-MG concentrations with ELISA. RESULTS: The results showed that, with regard to severe lesions, smokers had a significantly lower concentration of alpha-2-MG as well as significantly lower total amounts of alpha-2-MG and alpha-1-AT than non-smokers. With regard to moderate lesions, smokers tended to exhibit a lower concentration of alpha-2-MG, but the difference was not statistically significant. Comparing moderate and severe lesions, smokers exhibited no gradual increase with disease severity in contrast to non-smokers, who showed significantly or almost significantly increased levels of LF and alpha-2-MG in severe as compared to moderate lesions. CONCLUSIONS: The present results indicate that the levels of alpha-2-MG and alpha-1-AT are suppressed in smokers with periodontitis, suggesting that smoking interferes with these protease inhibitors. This may be one mechanism by which smoking affects the inflammatory response.

Adult↗
PubMed2001

Intracerebral microdialysis in neurointensive care: the use of urea as an endogenous reference compound.

OBJECT: When evaluating the results of intracerebral microdialysis, the in vivo performance of the microdialysis probe must be considered, because this determines the fraction of the interstitial concentration obtained in the microdialysis samples. The in vivo performance is dependent on several factors, for example, the interstitial compartment's diffusion characteristics, which may vary during the course of the acute brain injury process. In the present study the authors investigated the method of controlling the in vivo performance by using urea, which is evenly distributed in all body fluid compartments, as an endogenous reference compound and by comparing the urea levels in three compartments: the brain (CNS), abdominal subcutaneous tissue (SC), and blood serum (BS). METHODS: Sixty-nine patients with traumatic brain injury or cerebrovascular disease were included in the study. In 63 of these patients a CNS probe was used, an SC probe was used in 40, and both were used in 34. Urea was measured by enzymatic methods, at bedside for the microdialysis samples and in routine clinical laboratory studies for the BS samples, with the probe calibrated to give identical results. The correlation coefficient for CNS/SC urea was 0.88 (2414 samples), for CNS/BS urea it was 0.89 (180 samples), and for SC/BS urea it was 0.98 (112 samples). CONCLUSIONS: Urea levels in the CNS, SC, and BS were highly correlated, which supports the assumption that urea is evenly distributed. The CNS/SC urea ratio can therefore be used for monitoring the CNS probe's in vivo performance. Fluctuations in other substances measured with microdialysis are probably caused by biological changes in the brain, as long as the CNS/SC urea ratio remains constant.

Adipose Tissue↗
PubMed2000

[Low malignancy grade glioma in the Uppsala++/Orebro region. Prognostic factors and survival among 119 patients].

The benefit of surgery and radiotherapy for patients with low-grade gliomas is controversial. We studied case records of 119 patients diagnosed with low-grade glioma during 1987-1993 at our hospital. Statistical analysis was made on overall survival and on survival related to histological diagnosis and treatment modality. A large variation in survival of patients with similar histological diagnosis was seen. No correlation was found between survival and treatment modality. This clinical diversity probably reflects variations in tumor biological characteristics of low-grade gliomas. Greater understanding of the biology of these tumors will thus be needed for more effective therapies.

Adolescent↗
PubMed2000

Increased translation efficiency and antizyme-dependent stabilization of ornithine decarboxylase in amino acid-supplemented human colon adenocarcinoma cells, Caco-2.

The mechanisms of the response of ornithine decarboxylase(ODC), the rate-limiting enzyme in polyamine biosynthesis, to amino acid supplementation were studied in the human colon adenocarcinoma cell line, Caco-2. Supplementation of serum-deprived, subconfluent Caco-2 cells with any one of a series of amino acids (10 mM) resultedin increased ODC activity, reaching a maximum of approx. 12.5-fold after approx. 4 h, over control cells either not supplemented or supplemented with iso-osmolar D-mannitol. Glycine, L-asparagine and L-serine, as well as their D-enantiomers, were the strongest effectors and acted in a concentration-dependent manner; millimolar concentrations of most of these amino acids being sufficient to significantly increase ODC activity. In contrast, supplementation with D-methionine, L-lysine, L-aspartate or L-glutamate had little or no effect on ODC activity, whereas supplemental L-methionine, L-arginine, L-ornithine or L-cysteine was inhibitory. Polyamine assays showed that the putrescine content of cells varied in accordance with the changes in ODC activity. Western-blot and Northern-blot analyses revealed specifically increased levels of ODC protein but not mRNA,respectively, in response to supplementation with an ODC-inducing amino acid. Suppression of the increase in cycloheximide-treated cellsconfirmed a requirement for protein synthesis. Pulse-labelling of cellswith [(35)S]methionine showed a 3-fold increase in thesynthesis of ODC protein after 4 h of supplementation with glycineor L-serine. Supplemental glycine also augmented, reversibly, the half-life of ODC by almost 4-fold and simultaneously decreased the activity of putrescine-induced free antizyme. These results suggest that translational, but not transcriptional, regulation of ODC takes part in ODC induction by amino acids in Caco-2 cells. However, it also appears to occur in concert with decreased enzyme in activation and/or degradation.

Amino Acids↗
PubMed2000

A bone sialoprotein-binding protein from Staphylococcus aureus: a member of the staphylococcal Sdr family.

Staphylococcus aureus bacteria, isolated from bone and joint infections, specifically interact with bone sialoprotein (BSP), a glycoprotein of bone and dentine extracellular matrix, via a cell-surface protein of M(r) 97000 [Yacoub, Lindahl, Rubin, Wendel, Heinegârd and Rydén, (1994) Eur. J. Biochem. 222, 919-925]. Amino acid sequences of seven trypsin fragments from the 97000-M(r) BSP-binding protein were determined. A gene encoding a protein encompassing all seven peptide sequences was identified from chromosomal DNA isolated from S. aureus strain O24. This gene encodes a protein with 1171 amino acids, called BSP-binding protein (Bbp), which displays similarity to recently described proteins of the Sdr family from S. aureus. SdrC, SdrD and SdrE encode putative cell-surface proteins with no described ligand specificity. Bbp also shows similarity to a fibrinogen-binding protein from S. epidermidis called Fbe. A serine-aspartic acid repeat sequence was found close to the cell-wall-anchoring Leu-Pro-Xaa-Thr-Gly sequence in the C-terminal end of the protein. Escherichia coli cells were transformed with an expression vector containing a major part of the bbp gene fused to the gene for glutathione S-transferase. The affinity-purified fusion protein bound radiolabelled native BSP, and inhibited the binding of radiolabelled BSP to staphylococcal cells. Serum from patients suffering from bone and joint infection contained antibodies that reacted with the fusion protein of the BSP-binding protein, indicating that the protein is expressed during an infection and is immunogenic. The S. aureus Bbp protein may be important in the localization of bacteria to bone tissue, and thus might be of relevance in the pathogenicity of osteomyelitis.

Amino Acid Sequence↗
PubMed2000

On-line size-exclusion chromatography/electrospray ionisation mass spectrometry of aquatic humic and fulvic acids

Isolated aquatic humic and fulvic acids were analysed with on-line size exclusion chromatography/electrospray ionisation mass spectrometry (SEC/ESI-MS). An eluent composition which enabled electrospray ionisation was identified. The SEC separation improved interpretability of mass spectra and may open up new possibilities for molecular weight determination of humic substances. A linear dose-response relationship over a factor of 20 was obtained and the limit of detection was 50ng/uL for humic and fulvic acids. Spectral changes due to different ionisation conditions (pH and cone voltage) were investigated. A natural water sample from a Swedish lake was analysed. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗
PubMed2000

Hypoxanthine, uric acid and allantoin as indicators of in vivo free radical reactions. Description of a HPLC method and human brain microdialysis data.

A practical one-step high performance liquid chromatography (HPLC) method was developed for the simultaneous determination of hypoxanthine, uric acid and allantoin in small (4 microL) microdialysis samples. The rationale for this work was the current interest in hypoxanthine as a marker for energy perturbation in hypoxia/ ischemia, in uric acid as an endogenous antioxidant, and in allantoin as a marker for in vivo formation of reactive oxygen species (ROS). The method is based on ion pairing reversed phase chromatography and UV detection. The coefficient of variance for within and between run imprecision was generally below 5%, somewhat higher for concentrations close to the detection limit (0.4-1.0 pmoles). Recoveries ranged from 89 to 102% and linearity was observed in the concentration range from 0.25 to 25.0 mmol/L. There was an excellent correlation between the present method and available reference methods. The method was applied to cerebral microdialysis samples from a patient with severe subarachnoid haemorrhage complicated by secondary ischemia leading to cerebral infarction. The secondary ischemia was associated with an increase of hypoxanthine followed by increasing allantoin and uric acid levels. We submit that this pattern of chemical changes indicates increased ROS formation produced by secondary ischemia. The HPLC method appears to be a useful tool for studying changes of hypoxanthine, uric acid and allantoin levels in microdialysis samples.

Allantoin↗
PubMed2000

Improvements in quantitative source preparation

Quantitative source preparation is indispensable for radionuclide standardisation. To improve the source quality, a device has been developed to accelerate the evaporation of solvents from a drop deposited on a substrate. Short drying times were reached by stirring the rotating drop with multiple jets of dry nitrogen at elevated temperature. Uniform deposits with a large number of small crystals were obtained. The source-quality was checked by micrographs and scans of autoradiographs and by the shape parameters of alpha-particle spectra.

Journal Article↗
PubMed2000

Standardisation of 204Tl at IRMM

IRMM participated in a recent international comparison for the standardisation of a 204Tl solution organised by BIPM. The activity concentration of the 204Tl solution was measured at IRMM using 3 independent methods; Liquid Scintillation Counting using the CIEMAT/NIST method, 4pi-CsI counting and 4pibeta counting using a large pressurised proportional counter. This article describes the measurements in detail and discusses potential problems in the standardisation of 204Tl.

Journal Article↗