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Biomedical subjects

M Karlsson

Publications and source records attributed to M Karlsson.

At least 37 records · Page 2Linked to original sources

Photoneutron yields from tungsten in the energy range of the giant dipole resonance.

Photoneutron production on the nuclei of high-Z components of medical accelerator heads can lead to a significant secondary dose during a course of bremsstrahlung radiotherapy. However, a quantitative evaluation of secondary neutron dose requires improved data on the photoreaction yields. These have been measured as a function of photon energy, neutron energy and neutron angle for natW, using tagged photons at the MAX-Lab photonuclear facility in Sweden. This work presents neutron yields for natW(gamma, n) and compares these with the predictions of the Monte Carlo code MCNP-GN, developed specifically to simulate photoneutron production at medical accelerators.

Monte Carlo Method↗

Compton scattering from the deuteron and extracted neutron polarizabilities.

Differential cross sections for Compton scattering from the deuteron were measured at MAX-Lab for incident photon energies of 55 and 66 MeV at nominal laboratory angles of 45 degrees, 125 degrees, and 135 degrees. Tagged photons were scattered from liquid deuterium and detected in three NaI spectrometers. By comparing the data with theoretical calculations in the framework of a one-boson-exchange potential model, the sum and the difference of the isospin-averaged nucleon polarizabilities, alpha(N)+beta(N)=17.4+/-3.7 and alpha(N)-beta(N)=6.4+/-2.4 (in units of 10(-4) fm(3)), have been determined. By combining the latter with the global-averaged value for alpha(p)-beta(p) and using the predictions of the Baldin sum rule for the sum of the nucleon polarizabilities, we have obtained values for the neutron electric and magnetic polarizabilities of alpha(n)=8.8+/-2.4(total)+/-3.0(model) and beta(n)=6.5-/+2.4(total)-/+3.0(model), respectively.

Journal Article↗

Initial in vitro interaction of osteoblasts with nano-porous alumina.

In the present study we have used a characterised primary human cell culture model to investigate cellular interactions with nano-porous alumina. This material, prepared by anodisation, is being developed as a coating on titanium alloy implants. The structure of the alumina, as determined by X-ray diffraction and transmission electron microscopy, was amorphous. When studying cell/material interactions we used both biochemical and morphological parameters. Cell viability, proliferation and phenotype were assessed by measurement of redox reactions in the cells, cellular DNA, tritiated thymidine ([3H]-TdR) incorporation and alkaline phosphatase (ALP) production. Results showed a normal osteoblastic growth pattern with increasing cell numbers during the first 2 weeks. A peak in cell proliferation was seen on day 3, after which cell growth decreased, followed by an increase in ALP production, thus indicating that the osteoblastic phenotype was retained on the alumina. Cell adhesion was observed, the osteoblast-like cells having a flattened morphology with filipodia attached to the pores of the material. SDS-PAGE and western blot measurements showed that the nano-porous alumina was able to adsorb fibronectin. Trace amounts of aluminium ions were measured in the surrounding medium, but no adverse effect on cell activity was observed.

Adsorption↗

Antimicrobial susceptibility testing of porcine Brachyspira (Serpulina) species isolates.

No standardized method for susceptibility testing of Brachyspira spp. is currently available. A broth dilution procedure was evaluated and used to test the activities of six antimicrobial agents for 108 isolates of Swedish porcine Brachyspira spp. representing biochemical groups I, II, and III. Group I corresponds to Brachyspira hyodysenteriae, group II corresponds to B. intermedia, and group III corresponds to B. murdochii and B. innocens. A panel was designed with the antimicrobial agents dried in tissue culture trays with wells that allowed a liquid volume of 0.5 ml in each and agitation of the broth when incubated on a shaker. The MICs were determined by using brain heart infusion broth with 10% fetal calf serum. For 10 isolates, the results obtained in broth were compared to the MICs obtained on two different types of agar. Different inoculum densities and incubation times were also compared. The concentrations at which 90% of the B. hyodysenteriae isolates (n = 72) were inhibited in the broth dilution test by tiamulin (0.25 micro g/ml), tylosin (>256 micro g/ml), erythromycin (>256 micro g/ml), clindamycin (>4 micro g/ml), virginiamycin (4 micro g/ml), and carbadox (0.06 micro g/ml) were determined. The MICs tended to be lower in broth than on agar. Differences in inoculum densities and incubation times had little influence on the MICs. The evaluated broth dilution test was simple to perform, the end points were easily read, and the results were reproducible and reliable. No isolates with decreased susceptibility to tiamulin were found among the Swedish isolates tested.

Animals↗

Molecular imaging using hyperpolarized 13C.

MRI provides unsurpassed soft tissue contrast, but the inherent low sensitivity of this modality has limited the clinical use to imaging of water protons. With hyperpolarization techniques, the signal from a given number of nuclear spins can be raised more than 100 000 times. The strong signal enhancement enables imaging of nuclei other than protons, e.g. (13)C and (15)N, and their molecular distribution in vivo can be visualized in a clinically relevant time window. This article reviews different hyperpolarization techniques and some of the many application areas. As an example, experiments are presented where hyperpolarized (13)C nuclei have been injected into rabbits, followed by rapid (13)C MRI with high spatial resolution (scan time <1 s and 1.0 mm in-plane resolution). The high degree of polarization thus enabled mapping of the molecular distribution within various organs, a few seconds after injection. The hyperpolarized (13)C MRI technique allows a selective identification of the molecules that give rise to the MR signal, offering direct molecular imaging.

Animals↗

Referring TB suspects from private pharmacies to the National Tuberculosis Programme: experiences from two districts in Ho Chi Minh City, Vietnam.

SETTING: Ho Chi Minh City, Vietnam. OBJECTIVE: To describe pharmacists' attitudes towards referring TB suspects to the National Tuberculosis Programme (NTP) and to evaluate the feasibility of a new referral system. METHODS: 1) Questionnaire survey of 150 private pharmacies; 2) qualitative interviews with 16 pharmacists; 3) monitoring the use of new referral forms for 21 months. RESULTS: Use of a simple referral form was thought to be manageable by 72% of the pharmacists. Pharmacists identified a number of different types of risks associated with referral of TB suspects to the NTP; clients could turn to another pharmacy (61% of respondents); criticise the pharmacist if it appears that they do not have TB (42%); or remain untreated because they are not able to visit the NTP (41%). Fifty-eight (39%) of eligible pharmacies referred at least one client. At least 373 suspects were referred, 149 were tested and 10 had TB. CONCLUSIONS: It is feasible to let pharmacies refer TB suspects. For there to be a significant impact on case detection, it is important to acknowledge a number of concerns expressed by pharmacists and attempt to change both clients' and providers' expectations with regard to the pharmacists' role.

Adult↗

Noninvasive measurement of time-varying three-dimensional relative pressure fields within the human heart.

Understanding cardiac blood flow patterns is important in the assessment of cardiovascular function. Three-dimensional flow and relative pressure fields within the human left ventricle are demonstrated by combining velocity measurements with computational fluid mechanics methods. The velocity field throughout the left atrium and ventricle of a normal human heart is measured using time-resolved three-dimensional phase-contrast MRI. Subsequently, the time-resolved three-dimensional relative pressure is calculated from this velocity field using the pressure Poisson equation. Noninvasive simultaneous assessment of cardiac pressure and flow phenomena is an important new tool for studying cardiac fluid dynamics.

Atrial Function, Left↗

Subtle differences in dissociation rates of interactions between destabilized human carbonic anhydrase II mutants and immobilized benzenesulfonamide inhibitors probed by a surface plasmon resonance biosensor.

The development of commercial biosensors based on surface plasmon resonance has made possible careful characterization of biomolecular interactions. Here, a set of destabilized human carbonic anhydrase II (HCA II) mutants was investigated with respect to their interaction kinetics with two different immobilized benzenesulfonamide inhibitors. Point mutations were located distantly from the active site, and the destabilization energies were up to 23 kJ/mol. The dissociation rate of wild-type HCA II, as determined from the binding to the inhibitor with higher affinity, was 0.019 s(-1). For the mutants, dissociation rates were faster (0.022-0.025 s(-1)), and a correlation between faster dissociation and a high degree of destabilization was observed. We interpreted these results in terms of increased dynamics of the tertiary structures of the mutants. This interpretation was supported by entropy determinations, showing that the entropy of the native structure significantly increased upon destabilization of the protein molecule. Our findings demonstrate the applicability of modern biosensor technology in the study of subtle details in molecular interaction mechanisms, such as the long-range effect of point mutations on interaction kinetics.

Biosensing Techniques↗

Exon-intron organization and chromosomal localization of the mouse monoglyceride lipase gene.

Monoglyceride lipase (MGL) functions together with hormone-sensitive lipase to hydrolyze intracellular triglyceride stores of adipocytes and other cells to fatty acids and glycerol. In addition, MGL presumably complements lipoprotein lipase in completing the hydrolysis of monoglycerides resulting from degradation of lipoprotein triglycerides. Cosmid clones containing the mouse MGL gene were isolated from a genomic library using the coding region of the mouse MGL cDNA as probe. Characterization of the clones obtained revealed that the mouse gene contains the coding sequence for MGL on seven exons, including a large terminal exon of approximately 2.6 kb containing the stop codon and the complete 3' untranslated region. Two different 5' leader sequences, diverging 21 bp upstream of the predicted translation initiation codon, were isolated from a mouse adipocyte cDNA library. Western blot analysis of different mouse tissues revealed protein size heterogeneities. The amino acid sequence derived from human MGL cDNA clones showed 84% identity with mouse MGL. The mouse MGL gene was mapped to chromosome 6 in a region with known homology to human chromosome 3q21.

3' Untranslated Regions↗

"Tolerosomes" are produced by intestinal epithelial cells.

The development of immunological tolerance to orally fed antigens depends on the sampling, processing and transportation events followed in the intestinal epithelium. We present here a description of a "tolerosome": a supra-molecular, exosome-like structure assembled in and released from the small intestinal epithelial cell. The tolerosome is a approximately 40 nm large vesicular structure that carries MHC class II (MHC II) with bound antigenic peptides sampled from the gut lumen. Tolerosomes isolated from serum shortly after antigen feeding or from an in vitro pulsed intestinal epithelial cell line are fully capable of inducing antigen specific tolerance in naive recipient animals. Purified tolerosomes represent a structure by which fed antigens can be efficiently presented to the immune system. Removal of the tolerosomes from serum by ultracentrifugation or absorption of MHC II results in abrogated tolerance development.

Animals↗

Estimation of relative cardiovascular pressures using time-resolved three-dimensional phase contrast MRI.

Accurate, easy-to-use, noninvasive cardiovascular pressure registration would be an important addition to the diagnostic armamentarium for assessment of cardiac function. A novel noninvasive and three-dimensional (3D) technique for estimation of relative cardiovascular pressures is presented. The relative pressure is calculated using the Navier-Stokes equations along user-defined lines placed within a time-resolved 3D phase contrast MRI dataset. The lines may be either straight or curved to follow an actual streamline. The technique is validated in an in vitro model and tested on in vivo cases of normal and abnormal transmitral pressure differences and intraaortic flow. The method supplements an intuitive visualization technique for cardiovascular flow, 3D particle trace visualization, with a quantifiable diagnostic parameter estimated from the same dataset.

Adult↗

Pregnancy and lactation confer reversible bone loss in humans.

The influence of pregnancy on bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DXA) in 73 women (mean age 29 years, range 20-44 years) postpartum. Fifty-five age-matched women served as controls. The influence of lactation was evaluated in 65 of the delivered women who were followed with repeated measurements, a mean of 4.5 +/- 0.1 and 11.5 +/- 0.1 months after the delivery. The influence of multiple pregnancies was evaluated in 39 premenopausal women (mean age 38 years, range 31-54 years) with a minimum of four pregnancies (range 4-7). Fifty-eight age-matched healthy premenopausal women with a maximum of two pregnancies (range 0-2) served as controls. Data are presented as mean +/- SEM. BMD data are adjusted for differences in total fat mass and total lean mass. Lumbar spine BMD was 7.6 +/- 0.1% and total body BMD 3.9 +/- 0.1% lower in women postpartum compared with controls (both p<0.001). BMD did not decrease significantly in non-breastfeeding mothers. Mothers breastfeeding for 1-6 months decreased femoral neck BMD by 2.0 +/- 1.0% during the first 5 months postpartum (p<0.001). No further BMD loss was seen between 5 and 12 months postpartum. Femoral neck BMD 12 months after delivery was 1.3 +/- 0.8% lower than after delivery in mothers breastfeeding for 1-6 months (p = 0.05). Mothers breastfeeding for more than 6 months decreased Ward's triangle BMD by 8.5 +/- 1.0% and lumbar spine BMD by 4.1 +/- 0.8% during the first 5 months postpartum (both p<0.05). No further BMD loss was seen between 5 and 12 months postpartum. Femoral neck BMD 12 months after delivery was 4.0 +/- 1.1% lower and Ward's triangle BMD 5.3 +/- 1.9% lower than after delivery in mothers breastfeeding for more than 6 months (both p<0.05). BMD loss was higher during the first 5 months following delivery in the lactating women compared with the non-lactating women (p<0.05 comparing lumbar spine BMD loss in lactating mothers versus non-lactating mothers). However, in women with a minimum of four pregnancies the BMD was no lower than in age-matched women with fewer pregnancies. Total duration of lactation was not correlated with the present BMD. In summary, pregnancy seem to confer a low BMD with additional BMD loss during 5 months of lactation. Even if complete restoration in BMD was not reached within 5 months of weaning, women with four pregnancies or more had a BMD no lower than women with two pregnancies or fewer. We conclude that neither an extended lactation period nor multiple pregnancies could be used as a risk factor when predicting women at risk for future osteoporosis.

Absorptiometry, Photon↗

Infrared spectra of phthalic acid, the hydrogen phthalate ion, and the phthalate ion in aqueous solution.

The infrared spectra of a series of aqueous solutions containing phthalic acid (1,2-benzenedicarboxylic acid) and varying pH were examined using attenuated total reflection Fourier transform infrared spectroscopy and potentiometry. The basis spectra of phthalic acid, the hydrogen phthalate ion, and the phthalate ion were isolated using a factor analysis in which the absorbance of these species varies with pH and total phthalate concentration according to equilibrium and mass balance relations. Assignments of these basis spectra were made by comparison with spectra calculated ab initio. The conditional formation constants of phthalic acid and the hydrogen phthalate ion were determined at 25.0+/-0.1 degrees C in 0.6 M NaCl ionic media using infrared spectroscopy and in 1.5 M NaCl ionic media using both infrared spectroscopy and potentiometry.

Carboxylic Acids↗

Effect of glycogen loading on skeletal muscle cross-sectional area and T2 relaxation time.

This study was performed to investigate if glycogen loading of skeletal muscles, by binding water, would effect the cross-sectional area (CSA) and if an altered water content would alter the transverse relaxation time (T2) measured by magnetic resonance imaging (MRI). Five healthy volunteers participated in a programme with 4 days of extremely carbohydrate-restricted meals followed by 4 days of extremely high carbohydrate intake. The CSA and T2 of thigh and calf muscles were related to the intramuscular glycogen content evaluated at days 4 and 8. An increase in glycogen content from 281 to 634 mmol kg(-1) dry wt increased the CSA of the vastus muscles by 3.5% from 78 +/- 11 to 80 +/- 12 cm2 and the thigh circumference by 2.5% from 146 +/- 20 to 150 23 cm2. Calf circumference increased non-significantly by 4% from 78 +/- 15 to 82 +/- 19 cm2. Mono-exponential T2 decreased in m. tibialis anterior from 27.8 +/- 1.2 to 26.9 +/- 1.7 ms, did not change in m. vastus lateralis 26.5 +/- 1.9 ms/26.6 +/- 1.3 ms or in m. gastrocnemius 29.5 +/- 1.0 ms/29.8 +/- 1.9 ms. Glycogen loading increased the signal intensity mainly at different echo times (TE) 15 and 30 ms. The study shows that increased glycogen filling in the muscles increases muscle CSA and that this can be detected by MRI. The signal intensity increased the most at shorter TEs suggesting a more tight intracellular binding of water in glycogen loaded muscles.

Adult↗

The pleuromutilin drugs tiamulin and valnemulin bind to the RNA at the peptidyl transferase centre on the ribosome.

The pleuromutilin antibiotic derivatives, tiamulin and valnemulin, inhibit protein synthesis by binding to the 50S ribosomal subunit of bacteria. The action and binding site of tiamulin and valnemulin was further characterized on Escherichia coli ribosomes. It was revealed that these drugs are strong inhibitors of peptidyl transferase and interact with domain V of 23S RNA, giving clear chemical footprints at nucleotides A2058-9, U2506 and U2584-5. Most of these nucleotides are highly conserved phylogenetically and functionally important, and all of them are at or near the peptidyl transferase centre and have been associated with binding of several antibiotics. Competitive footprinting shows that tiamulin and valnemulin can bind concurrently with the macrolide erythromycin but compete with the macrolide carbomycin, which is a peptidyl transferase inhibitor. We infer from these and previous results that tiamulin and valnemulin interact with the rRNA in the peptidyl transferase slot on the ribosomes in which they prevent the correct positioning of the CCA-ends of tRNAs for peptide transfer.

Anti-Bacterial Agents↗

The evidence that exercise during growth or adulthood reduces the risk of fragility fractures is weak.

There has never been, and will never be, a randomized double-blind placebo-controlled trial demonstrating that exercise in youth, adulthood or old age reduces fragility or osteoporosis-related fractures in old age. The next level of evidence, a randomized, controlled but unblinded study with fractures as an end-point is feasible but has never been done. The basis for the belief that exercise reduces fractures is derived from lower levels of 'evidence', namely, retrospective and prospective observation cohort studies and case-control studies. These studies are at best hypothesis generating, never hypothesis testing. They are all subject to many systematic biases and should be interpreted with extreme scepticism. Surrogate measures of anti-fracture efficacy are the next level of evidence, such as the demonstration of a reduction in risk factors for falls, a reduction in falls, a reduction in fractures due to falls, an increase in peak bone size and mass, prevention of bone loss in midlife and restoration of bone mass and structure in old age.

Adolescent↗

Follow-up of patients treated with oral doxycycline for Lyme neuroborreliosis.

The clinical outcome for 69 patients treated with oral doxycycline for Lyme neuroborreliosis was studied retrospectively. The clinical follow-up time was 14 d to 2 y (median 7 months). All patients improved during and after treatment. A complete recovery was seen in 56 patients by 14 d to 9 months (median 6 weeks) after therapy, while 13 patients (19%) still had persistent sequelae 1 y after antibiotic treatment. Six patients were retreated because of new or persistent symptoms, but in no patient was a treatment failure proven. A questionnaire was sent to each patient, asking for time to recovery, sequelae and relapse of symptoms. No patient had experienced relapse of symptoms associated with Lyme neuroborreliosis when answering the questionnaire 2-9 y after treatment. Oral doxycycline seems to be an effective, convenient and inexpensive alternative for the treatment of Lyme neuroborreliosis.

Administration, Oral↗