Search PubMed⌕ Search

Biomedical subjects

M Karlsson

Publications and source records attributed to M Karlsson.

At least 91 records · Page 5Linked to original sources
PubMed1999

Muscular and neurologic function in patients with recurrent dislocation after total hip arthroplasty: a matched controlled study of 65 patients using dual-energy X-ray absorptiometry and postural stability tests.

Twenty-two patients with recurrent dislocation after primary total hip arthroplasty (THA) were compared with 43 randomly selected, stratified THA patients without dislocation with regard to radiographic cup position; body composition of bone, fat, and muscle (lean body mass) as determined by dual-energy x-ray absorptiometry; strength in abduction and adduction; range of motion; balance; and vibration sense. Balance and sensitivity to vibration were impaired in the patients with dislocation. No differences were found in any other variables except a subset of tall men in the dislocation group.

Absorptiometry, Photon↗
PubMed1999

Pitfalls in Doppler evaluation of diastolic function: insights from 3-dimensional magnetic resonance imaging.

Ultrasound-Doppler assessment of diastolic function is subject to velocity errors caused by angle sensitivity and a fixed location of the sample volume. We used 3-dimensional phase contrast magnetic resonance imaging (MRI) to evaluate these errors in 10 patients with hypertension and in 10 healthy volunteers. The single (Doppler) and triple (MRI) component velocity was measured at early (E) and late (A) inflow along Doppler-like sample lines or 3-dimensional particle traces generated from the MRI data. Doppler measurements underestimated MRI velocities by 9.4% +/- 8.6%; the effect on the E/A ratio was larger and more variable. Measuring early and late diastolic inflows from a single line demonstrated the error caused by their 3-dimensional spatial offset. Both errors were minimized by calculating the E/A ratio from maximal E and A values without constraint to a single line. Alignment and spatial offset are important sources of error in Doppler diastolic parameters. Improved accuracy may be achieved with the use of maximal E and A velocities from wherever they occur in the left ventricle.

Adult↗
PubMed1999

Aquaporins and water homeostasis in plants.

Aquaporins are water channel proteins of vacuolar and plasma membranes. When opened they facilitate the passive movement of water molecules down a water potential gradient. In Arabidopsis, 30 genes have been found that code for aquaporin homologues. Some of these genes code for highly abundant constitutively expressed proteins and some are known to be temporally and spatially regulated during development and in response to stress. The water transport activity of two aquaporins is regulated at the protein level by phosphorylation and dephosphorylation. At a given time, cells express several different aquaporins, and it is probable that vacuolar and plasma membrane aquaporins acting in concert are responsible for the cytosolic osmoregulation that is necessary for maintaining normal metabolic processes. Inhibition studies of aquaporins in vivo and antisense mutant studies suggest that, in addition to cytosolic osmoregulation, aquaporins are important for the bulk flow of water in plants.

Journal Article↗
PubMed1999

Methods for the determination of effective monitor chamber thickness.

There are a number of models, both analytical and Monte Carlo, which are used to describe the fluence from the treatment head of accelerators. One common problem in these simulations is to find relevant information about details in the treatment head. A complex unit in the treatment head for which reliable data is seldom given is the monitor chamber. In this work two methods are described for obtaining this information by analyzing the increased scattering of an electron beam when the monitor chamber is introduced in the beam. It was found that the effective thickness of the electrodes in a monitor chamber can be determined with sufficient accuracy by using experimental results combined with Fermi-Eyges theory or Monte Carlo simulations.

Biophysical Phenomena↗
PubMed1999

Treatment head design for multileaf collimated high-energy electrons.

This paper describes how a conventional treatment head can be modified for use of multileaf collimated electron beams. Automatic and dynamic beam delivery are possible for both electrons and photons by using the computer controlled multileaf collimator (MLC) for both photon and electron beams. Thereby, the electron beams can be mixed more freely into the treatment to take advantage of the specific depth modulation characteristics of electrons. The investigation was based on Monte Carlo calculations using the software package BEAM. The physical parameters used in this optimization were the beam penumbra and the virtual/effective point source position. These parameters are essential for shaping beams, beam matching and for dosimetry calculations. The optimization was carried out by modifying a number of parameters: replacing the air atmosphere in the treatment head with helium, adding a helium bag below the MLC, changing the position of the scattering foils, modifying the monitor chamber, and adjusting the position of the MLC. The beam characteristics for some of these designs were found to fulfil our criteria for clinically useful beams down to at least 9 MeV.

Computer Simulation↗
PubMed1999

Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF Study Group.

To determine the incidence and 90-d mortality of acute respiratory failure (ARF), acute lung injury (ALI), and the acute respiratory distress syndrome (ARDS), we carried out an 8-wk prospective cohort study in Sweden, Denmark, and Iceland. All intensive care unit (ICU) admissions (n = 13,346) >/= 15 yr of age were assessed between October 6th and November 30th, 1997 in 132 of 150 ICUs with resources to treat patients with intubation and mechanical ventilation (I + MV) >/= 24 h. ARF was defined as I + MV >/= 24 h. ALI and ARDS were defined using criteria recommended by the American-European Consensus Conference on ARDS. Calculation to correct the incidence for unidentified subjects from nonparticipating ICUs was made. No correction for in- or out-migration from the study area was possible. The population in the three countries >/= 15 yr of age was 11.74 million. One thousand two hundred thirty-one ARF patients were included, 287 ALI and 221 ARDS patients were identified. The incidences were for ARF 77.6, for ALI 17.9, and for ARDS 13.5 patients per 100,000/yr. Ninety-day mortality was 41.0% for ARF, including ALI and ARDS patients, 42.2% for ALI not fulfilling ARDS criteria, and 41.2% for ARDS.

Acute Disease↗
PubMed1999

Localization of the insulin receptor in caveolae of adipocyte plasma membrane.

The insulin receptor is a transmembrane protein of the plasma membrane, where it recognizes extracellular insulin and transmits signals into the cellular signaling network. We report that insulin receptors are localized and signal in caveolae microdomains of adipocyte plasma membrane. Immunogold electron microscopy and immunofluorescence microscopy show that insulin receptors are restricted to caveolae and are colocalized with caveolin over the plasma membrane. Insulin receptor was enriched in a caveolae-enriched fraction of plasma membrane. By extraction with beta-cyclodextrin or destruction with cholesterol oxidase, cholesterol reduction attenuated insulin receptor signaling to protein phosphorylation or glucose transport. Insulin signaling was regained by spontaneous recovery or by exogenous replenishment of cholesterol. beta-Cyclodextrin treatment caused a nearly complete annihilation of caveolae invaginations as examined by electron microscopy. This suggests that the receptor is dependent on the caveolae environment for signaling. Insulin stimulation of cells prior to isolation of caveolae or insulin stimulation of the isolated caveolae fraction increased tyrosine phosphorylation of the insulin receptor in caveolae, demonstrating that insulin receptors in caveolae are functional. Our results indicate that insulin receptors are localized to caveolae in the plasma membrane of adipocytes, are signaling in caveolae, and are dependent on caveolae for signaling.

3T3 Cells↗
PubMed1998

Nerve growth factor receptor TrkA is expressed by horizontal and amacrine cells during chicken retinal development.

Nerve growth factor is known to stimulate neurite outgrowth and support neuronal survival during embryonic development. We have studied the expression of the nerve growth factor receptor, TrkA, at both mRNA and protein levels during the course of chicken retinal development. Furthermore, we have compared the expression of trkA mRNA with that of the 75-kD low-affinity neurotrophin receptor (p75NTR). RNase protection assay identified peak-levels of trkA mRNA in the late embryonic retina. Using in situ hybridization and immunohistochemistry, we found cells expressing TrkA in both the internal and the external part of the inner nuclear layer, corresponding to amacrine and horizontal cells, respectively. The TrkA-expressing amacrine cell has a unistratified dendritic arborization in the second sublamina of the inner plexiform layer, and may represent the stellate amacrine cell described by Cajal. The horizontal cells, possessing arciform dendrite processes in the outer plexiform layer, showed strong TrkA immunoreactivity in both dendrites and cell bodies. During the course of retinal development, the TrkA-expressing amacrine cells decreased in number, whereas the TrkA-expressing horizontal cells persisted. Because nerve growth factor was expressed where the horizontal cells, but not where the amacrine cells were located, these findings raise the question of whether nerve growth factor could locally support the survival of TrkA-expressing interneurons during retinal development.

Animals↗
PubMed1998

The manganese-containing ribonucleotide reductase of Corynebacterium ammoniagenes is a class Ib enzyme.

Ribonucleotide reductases (RNRs) are key enzymes in living cells that provide the precursors of DNA synthesis. The three characterized classes of RNRs differ by their metal cofactor and their stable organic radical. We have purified to near homogeneity the enzymatically active Mn-containing RNR of Corynebacterium ammoniagenes, previously claimed to represent a fourth RNR class. N-terminal and internal peptide sequence analyses clearly indicate that the C. ammoniagenes RNR is a class Ib enzyme. In parallel, we have cloned a 10-kilobase pair fragment from C. ammoniagenes genomic DNA, using primers specific for the known class Ib RNR. The cloned class Ib locus contains the nrdHIEF genes typical for class Ib RNR operon. The deduced amino acid sequences of the nrdE and nrdF genes matched the peptides from the active enzyme, demonstrating that C. ammoniagenes RNR is composed of R1E and R2F components typical of class Ib. We also show that the Mn-containing RNR has a specificity for the NrdH-redoxin and a response to allosteric effectors that are typical of class Ib RNRs. Electron paramagnetic resonance and atomic absorption analyses confirm the presence of Mn as a cofactor and show, for the first time, insignificant amounts of iron and cobalt found in the other classes of RNR. Our discovery that C. ammoniagenes RNR is a class Ib enzyme and possesses all the highly conserved amino acid side chains that are known to ligate two ferric ions in other class I RNRs evokes new, challenging questions about the control of the metal site specificity in RNR. The cloning of the entire NrdHIEF locus of C. ammoniagenes will facilitate further studies along these lines.

Amino Acid Sequence↗
PubMed1998

Kainic acid, tetrodotoxin and light modulate expression of brain-derived neurotrophic factor in developing avian retinal ganglion cells and their tectal target.

Increasing evidence underlies the importance of neurotrophins as neuron-derived trophic signals in the developing visual system, although their precise roles are still undefined. Here we show that brain-derived neurotrophic factor messenger RNA is simultaneously expressed in a subpopulation of retinal ganglion cells and in their target during late embryogenesis. Moreover, light as well as the excitotoxin; kainic acid, induced an increase of the brain-derived neurotrophic factor messenger RNA, which could be blocked by the sodium-channel blocker; tetrodotoxin. Messenger RNA for trkB, a receptor for brain-derived neurotrophic factor, was found in the retinal ganglion cells expressing brain-derived neurotrophic factor showing that certain retinal ganglion cells express messenger RNA both for brain-derived neurotrophic factor and trkB. Furthermore, trkB messenger RNA was found in tectum, in the same layers as the brain-derived neurotrophic factor messenger RNA. These findings suggest that brain-derived neurotrophic factor expression is regulated in an activity-dependent manner during the phase of development when neuronal activity plays an important role.

Animals↗
PubMed1998

Dacarbazine-vindesine versus dacarbazine-vindesine-cisplatin in disseminated malignant melanoma. A randomised phase III trial.

In a multicentre phase III study of disseminated malignant melanoma performed in Sweden and Norway, 326 patients were randomised to receive treatment with the combination dacarbazine [DTIC] (D) and vindesine (V) with or without the addition of cisplatin (P). D was given intravenously (i.v.) at a dose of 250 mg/m2 days 1-5 every 4 weeks and V was given i.v. at a dose of 3.0 mg/m2 day 1 weekly. P was given i.v. at a dose of 100 mg/m2 day 1 every 4 weeks. There was no statistically significant difference in overall survival between the treatment arms (P = 0.22). Increased toxicity was observed in the treatment arm containing P of which leucopenia, alopecia and nausea/vomiting were the most pronounced. The median time to progression was significantly longer in patients treated with DVP (4.2 versus 2.2 months, P = 0.007). In conclusion, adding P to DV did not change overall survival but did significantly increase toxicity.

Adolescent↗
PubMed1998

Measured lung dose correction factors for 50 MV photons.

Some clinically relevant measurements of lung tissue/water equivalent interfaces have been performed for a 50 MV therapeutic x-ray beam. The purpose was to investigate the severity of dose perturbation effects in lung tissue and adjacent tissues using an energy well above the common clinical practice in thoracic irradiations. The phantoms were constructed of solid water, PMMA and white polystyrene as soft tissue (water) equivalents, and cork was used as the lung tissue equivalent. Measurements were performed using radiographic film and a cylindrical ionization chamber. The results show that the degradation of the 20/80% beam penumbra in the lung region is severe, up to 2.5 times the penumbra in water for a 10 cm thick lung with a density of 0.30 x 10(3) kg m(-3). The lack of electronic equilibrium in the low-density region can cause underdosage at the lung/tumour interface of up to 30% of maximum target dose, and the build-up depth to 95% of target dose in unit density tissue behind the lung may be as large as 22 mm. It is also shown that these figures strongly depend on patient anatomy and beam size and why a careful calculation of the individual dose distribution is needed for optimal choice of photon beam energy in thoracic treatments.

Biophysical Phenomena↗
PubMed1998

Intensity modulation with electrons: calculations, measurements and clinical applications.

Intensity modulation of electron beams is one step towards truly conformal therapy. This can be realized with the MM50 racetrack microtron that utilizes a scanning beam technique. By adjusting the scan pattern it is possible to obtain arbitrary fluence distributions. Since the monitor chambers in the treatment head are segmented in both x- and y-directions it is possible to verify the fluence distribution to the patient at any time during the treatment. Intensity modulated electron beams have been measured with film and a plane parallel chamber and compared with calculations. The calculations were based on a pencil beam method. An intensity distribution at the multileaf collimator (MLC) level was calculated by superposition of measured pencil beams over scan patterns. By convolving this distribution with a Gaussian pencil beam, which has propagated from the MLC to the isocentre, a fluence distribution at isocentre level was obtained. The agreement between calculations and measurements was within 2% in dose or 1 mm in distance in the penumbra zones. A standard set of intensity modulated electron beams has been developed. These beams have been implemented in a treatment planning system and are used for manual optimization. A clinical example (prostate) of such an application is presented and compared with a standard irradiation technique.

Calibration↗
PubMed1998

Scanned intensity modulations for 50 MV photons.

Optimization of the dose distributions by individual beam compensation is a useful tool in conformal radiation therapy. Intensity modulation by electromagnetic scanning of a narrow elementary beam allows fast dose delivery and causes little change in beam quality compared with other methods, especially for high energies such as 50 MV. Intensity modulated beams from the MM50 accelerator were measured and compared with calculations based on Monte Carlo simulations. Good agreement between measurements and calculations were found, typically within 1% for central dose profiles. The steepest wedge angle that was produced with the scanning beam technique was of 45 degrees or 3.5% cm(-1) for a 20 cm x 20 cm field, slightly varying with depth. The elementary 50 MV photon 'pencil beam' for a full range, high-z bremsstrahlung target, is a wide dose distribution at 10 cm depth in water which limits the modulation gradient and hence the complexity of the modulation by the scanning of a photon pencil beam only. Scanned wedge beam distributions were modelled in the treatment planning system and a pelvic treatment with three fields was used to illustrate a clinical application. The resulting dose volume data were compared for different radiation qualities but with similar beam portals. 'Energy modulation' by field matching with lower photon energies was performed to sharpen the penumbra towards organs at risk.

Electromagnetic Fields↗
PubMed1998

Multivariate analysis of factors influencing repeat expansion detection.

Repeat expansion detection (RED) is a powerful tool for detection of expanded repeat sequences in the genome. In RED, DNA serves as a template for a repeat-specific oligonucleotide. A thermostable ligase is used to ligate oligonucleotides that have annealed at adjacent positions, creating multimers in a thermal cycling procedure. The products are visualized after gel electrophoresis, transfered to a membrane and subsequently hybridized. Multiple linear regression (MLR) and partial least square (PLS) techniques were used to reveal the most influential factors in the amplification reaction and to identify possible interacting factors. Ligation temperature proved to be the most important factor in the reaction: Temperatures far below the melting point of the oligonucleotide increased the yield considerably. Higher cycle number resulted in a continuous rise in intensity, indicating that the ligase remained active even after 700 cycles or 12 hr of cycling. In addition, the concentration of ligase was found to be important. Using optimal parameters, a 5.5- and 3.2-fold increase in the yield of 180- and 360-nucleotide products respectively was obtained. The improved sensitivity makes the method more robust and facilitates detection of repeat expansions. This improvement may be particularly useful in development of RED for diagnostic purposes as well as for nonradioactive detection of RED products. Based on these results, a new protocol for the RED method was developed taking into account the risk of introducing artifacts with increased enzyme concentrations and lowered annealing temperatures.

DNA↗
PubMed1998

Water transport activity of the plasma membrane aquaporin PM28A is regulated by phosphorylation.

PM28A is a major intrinsic protein of the spinach leaf plasma membrane and the major phosphoprotein. Phosphorylation of PM28A is dependent in vivo on the apoplastic water potential and in vitro on submicromolar concentrations of Ca2+. Here, we demonstrate that PM28A is an aquaporin and that its water channel activity is regulated by phosphorylation. Wild-type and mutant forms of PM28A, in which putative phosphorylation sites had been knocked out, were expressed in Xenopus oocytes, and the resulting increase in osmotic water permeability was measured in the presence or absence of an inhibitor of protein kinases (K252a) or of an inhibitor of protein phosphatases (okadaic acid). The results indicate that the water channel activity of PM28A is regulated by phosphorylation of two serine residues, Ser-115 in the first cytoplasmic loop and Ser-274 in the C-terminal region. Labeling of spinach leaves with 32P-orthophosphate and subsequent sequencing of PM28A-derived peptides demonstrated that Ser-274 is phosphorylated in vivo, whereas phosphorylation of Ser-115, a residue conserved among all plant plasma membrane aquaporins, could not be demonstrated. This identifies Ser-274 of PM28A as the amino acid residue being phosphorylated in vivo in response to increasing apoplastic water potential and dephosphorylated in response to decreasing water potential. Taken together, our results suggest an active role for PM28A in maintaining cellular water balance.

Animals↗
PubMed1998

Calculation of photon energy and dose distributions in a 50 MV scanned photon beam for different target configurations and scan patterns.

A method to characterize the energy distribution in the whole photon field is valuable when designing an accelerator for choosing target and flattening filter or scan pattern. Another field of application is beam characterization for treatment planning systems or other dosimetric purposes. This work is focused on the energy distribution in different 50 MV bremsstrahlung beams with different scanning of electrons on three different targets. Fluence differential in energy and angle at the exit of each target has been determined by Monte Carlo calculations for a narrow beam. Data for broad beams were obtained by convolution of the narrow beams with different scan patterns. Photon energy fluence differential in energy at SSD 100 were thus found to be rather different for the targets studied. The results are presented as mean energy profiles and narrow beam half-value layer (HVL) in water. Two different experimental setups were used to measure HVL at the central axis and at off-axis positions. The two methods gave results which differ by 5%-6% and the calculated data where within these experimental results. In conclusion, the presented method for characterization of the photon field energy distribution is well within the experimental results and can thus be used to improve accelerator design or dosimetric calculations, e.g., for treatment planning.

Biophysical Phenomena↗