Biomedical subjects

Marcus Larsson

Publications and source records attributed to Marcus Larsson.

10 recordsLinked to original sources

PubMed2006

An X-ray diffraction study of alterations in bovine lung surfactant bilayer structures induced by albumin.

Lung surfactant (LS) is an extra-cellular lipid-protein system responsible for maintaining low surface tension in the lung and alveolar stability. Serum proteins cause dysfunction of this material, e.g. in adult respiratory distress syndrome (ARDS). BLES is a clinically used LS consisting of most of the lipids and associated proteins from bovine lung lavage. Aqueous phases of BLES at 30% and 70% hydration, with and without 5% by weight of bovine serum albumin (BSA), calculated on the amount of lipids, were studied using X-ray diffraction during cooling from 42 to 5 degrees C. The diffraction curves are consistent with a transition from a lamellar liquid crystalline phase to a gel phase transition at cooling in the interval 30-20 degrees C. The long-spacings correspond to a reduction of the bilayer thickness during this transition. The wide-angle region shows a peak at 4.1 A below 25 degrees C, which is characteristic of the hexagonal chain packing of the gel phase. The perturbation of the bilayers by the presence of BSA seems to induce a significant decrease of the bilayer thickness. Calculations on the observed limits of swelling (taking place in the range 50-60%) indicate that BSA is closely associated with the BLES bilayers, probably due to electrostatic interaction with the cationic surfactant proteins SP-B and SP-C. This study show that the LS lipid structural organizations are extremely susceptible to small amounts of serum albumin, which may have implications in surfactant related lung disease and clinical applications of surfactant therapy.

Animals↗

PubMed2006

Contribution of religiousness in the prediction and interpretation of mystical experiences in a sensory deprivation context: activation of religious schemas.

M. A. Persinger (2002) claimed that transcranial magnetic stimulation with weak, complex magnetic fields evokes mystical experiences. However, in a double-blind experiment, P. Granqvist, M. Fredrikson, P. Unge, A. Hagenfeldt, S. Valind., et al. (2005) found no effects of field exposure on mystical experiences (N = 89), though a minority of participants reported spontaneous mystical experiences. Following the conclusion of null effects from magnetic field exposure, the setup of this experiment, including pre-experimental assessments of religiousness and sensory deprivation, can be viewed as a prime/setting for such experiences. The authors analyzed subsets of experimental data from P. Granqvist and colleagues with emphasis on the contribution of religiousness in the prediction and interpretation of mystical experiences. They found that a higher degree of religiousness predicted a higher occurrence of mystical experiences with a religious quality, but not of mystical experiences without such a quality. The authors discuss findings in terms of the experimental setup serving as a prime/setting activating the religious schemas of religious participants.

Adult↗

PubMed2005

Sensed presence and mystical experiences are predicted by suggestibility, not by the application of transcranial weak complex magnetic fields.

Transcranial magnetic stimulation (TMS) with weak (micro Tesla) complex waveform fields have been claimed to evoke the sensed presence of a sentient being in up to 80% in the general population. These findings have had a questionable neurophysiological foundation as the fields are approximately six orders of magnitude weaker than ordinary TMS fields. Also, no independent replication has been reported. To replicate and extend previous findings, we performed a double-blind experiment (N=89), with a sham-field control group. Personality characteristics indicating suggestibility (absorption, signs of abnormal temporal lobe activity, and a "new age"-lifestyle orientation) were used as predictors. Sensed presence, mystical, and other somatosensory experiences previously reported from the magnetic field stimulation were outcome measures. We found no evidence for any effects of the magnetic fields, neither in the entire group, nor in individuals high in suggestibility. Because the personality characteristics significantly predicted outcomes, suggestibility may account for previously reported effects. Our results strongly question the earlier claims of experiential effects of weak magnetic fields.

Adolescent↗

PubMed2003

In vivo determination of local skin optical properties and photon path length by use of spatially resolved diffuse reflectance with applications in laser Doppler flowmetry.

Methods for local photon path length and optical properties estimation, based on measured and simulated diffuse reflectance within 2 mm from the light source, are proposed and evaluated in vivo on Caucasian human skin. The accuracy of the methods was good (2%-7%) for path length and reduced scattering but poor for absorption estimation. Reduced scattering and absorption were systematically lower in the fingertip than in the forearm skin (633 nm). A maximum intrasite and interindividual variation of approximately 35% in an average photon path length was found. The methodology was applied in laser Doppler flowmetry, where path-length normalization of the estimated perfusion removed the optical property dependency.

Computer Simulation↗

PubMed2003

Human SP-A and a pharmacy-grade porcine lung surfactant extract can be reconstituted into tubular myelin--a comparative structural study of alveolar surfactants using cryo-transmission electron microscopy.

Cryo-transmission electron microscopy (cryo-TEM) is a rather artefact-free method, well suited to study the alveolar surfactant system. A pharmacy grade porcine lung surfactant extract (HL-10) was mixed with human SP-A and Ringer's solution (for calcium ions), and it was shown by cryo-TEM that the tubular myelin (TM) type of structure was reconstituted. These aggregates were associated to liposomal aggregates, and resulted in macroscopic phase-separation. This phase showed a weak birefringence in the polarising microscope, which is characteristic for a liquid-crystalline type of structure. TM from rabbit lung lavage was also examined, and showed the same periodic arrangement of bilayers as alveolar surface layer from freshly cut rabbit lungs deposited directly on the cryo-TEM grids. The distance between the bilayers of TM was 40-50 nm, and an electron dense material, assumed to be SP-A, was sometimes seen to occur periodically along the bilayers, oriented perpendicularly to the tubuli. The results are consistent with the surface-phase model of the alveolar lining.

Animals↗

PubMed2002

The bilayer melting transition in lung surfactant bilayers: the role of cholesterol.

Aqueous dispersions of a porcine lung surfactant (PLS) extract with and without cholesterol supplementation were analyzed by X-ray scattering. Lamellar liquid-crystalline and gel-type bilayer phases are formed, as in pure phosphatidylcholine (PC)-cholesterol systems. This PLS extract, developed for clinical applications, has a cholesterol content of less than 1% (w/w). Above the limit of swelling, the bilayer structure shows a melting (main) transition during heating at about 34 degrees C. When 13 mol% cholesterol was added to PLS, so that the cholesterol content of natural lung surfactant was reached, the X-ray scattering pattern showed pronounced changes. The main transition temperature was reduced to the range 20-25 degrees C, whereas according to earlier studies of disaturated PC-cholesterol bilayers in water the main transition remains almost constant when the amount of solubilized cholesterol is increased. Furthermore, the changes in scattering pattern at passing this transition in PLS-cholesterol samples were much smaller than at the same transition in PLS samples. These effects of cholesterol solubilization can be related to phase segregation within the bilayers, known from pure PC-cholesterol systems. One phase, solubilizing about 8 mol% cholesterol, exhibits a melting transition, whereas the other bilayer phase, with a liquid-crystalline disordered conformation, has a cholesterol content in the range 20-30 mol% and this phase shows no thermal transition. The relative amount of bilayer lipids that is transformed at the main transition in the PLS-cholesterol sample is therefore only half compared to that in PLS samples. The reduction in transition temperature in the segregated bilayer of lung surfactant lipids is probably an effect of enrichment of disaturated PC species in the phase, which is poor in cholesterol. This work indicates that cholesterol in lung surfactant regulates the crystallization behavior.

Animals↗

PubMed2002

Enhanced efficacy of porcine lung surfactant extract by utilization of its aqueous swelling dynamics.

This study investigates the interactions between a porcine lung surfactant (PLS) extract and distilled water, saline solution or Ringer solution. The phases which coexist in equilibrium with water or electrolyte solutions were analysed by X-ray diffraction and cryo transmission electron microscopy (cryo-TEM). A lamellar phase with a structure unit consisting of double bilayers was observed in water, whereas lamellar phases with the usual bilayer structure unit were formed in saline and in Ringer solutions. At 25 degrees C the presence of a 4.2-A peak in the X-ray diffraction wide-angle region of these three maximally swollen phases showed that most of the hydrocarbon chains were organized in a crystalline packing. At 42 degrees C the chains in all three phases were melted which, in combination with the low-angle diffraction, shows that they were liquid-crystalline. Polyhedral-like vesicles and spherically shaped multilamellar vesicles were observed in cryo-TEM. The bilayer unit structures were consistent with the periodicity seen by X-ray diffraction. The dynamic swelling behaviour was followed in the polarizing microscope. A remarkable growth of birefringent networks was seen at the air interface of samples swollen in Ringer solution and saline solution. No such interfacial growth phenomena were observed during swelling in water without electrolytes. Then, these dynamics were analysed in relation to time-dependent pulmonary administration of the surfactant extract in rats. Variation in the time of administration (20 and 60 min) after mixing the extract with saline or Ringer solution showed clear differences in physiological effects. At pulmonary administration when the swelling behaviour in vitro showed a maximum in dynamics, the arterial oxygenation was superior to that of administration at a time after a steady-state had been reached. This means that the clinical performance of mammalian lung surfactant extracts can be significantly improved by taking the time-dependent aqueous swelling of the extract into account.

Animals↗

PubMed2002

Influence of optical properties and fiber separation on laser doppler flowmetry.

Microcirculatory blood flow can be measured using a laser Doppler flowmetry (LDF) probe. However, the readings are affected by the tissue's optical properties (absorption and scattering coefficients, mu(a) and mu(s)) and probe geometry. In this study the influence of optical properties [mu(a)in(0.053,0.23) mm-1,mu(s)in(14.7,45.7) mm-1] on LDF perfusion and LDF sampling depth was evaluated for different fiber separations. In vitro measurements were made on a sophisticated tissue phantom with known optical properties that mimicked blood flow at different depths. Monte Carlo simulations were carried out to extend the geometry of the tissue phantom. A good correlation between measured and simulated data was found. The simulations showed that, for fixed flow at a discrete depth, the influence of mu(s) or mu(a) on LDF perfusion increased with an increase in flow depth and decreased with an increase in fiber separation. For a homogeneous flow distribution, however, the perfusion varied 40% due to variations in the optical properties, almost independent of the fiber separation (0.23-1.61 mm). Therefore, the effect in real tissue is likely to vary due to the unknown heterogeneous blood flow distribution. Further, the LDF sampling depth increased with a decrease in mu(s) or mu(a) and an increase in fiber separation. For fiber separation of 0.46 mm, the e-1 sampling depth ranged from 0.21 to 0.39 mm.

Blood Flow Velocity↗

PubMed2002

Photon pathlength determination based on spatially resolved diffuse reflectance.

A method for the prediction of the average photon pathlength in turbid media has been developed. The method is based on spatially resolved diffuse reflectance with discrete source detector distances up to 2 mm. Light reflectance was simulated using a Monte Carlo technique with a one-layer model utilizing a wide range of optical properties, relevant to human skin. At a source detector separation of 2 mm, the pathlength can vary sixfold due to differences in optical properties. By applying various preprocessing and prediction techniques, the pathlength can be predicted with a root-mean-square error of approximately 5%. Estimation of the photon pathlength can be used, e.g., to remove the influence of optical properties on laser Doppler flowmetry perfusion readings, which are almost linearly related to the average photon pathlength.

Biophysical Phenomena↗

PubMedDate not supplied

Toward a velocity-resolved microvascular blood flow measure by decomposition of the laser Doppler spectrum.

Tissue microcirculation, as measured by laser Doppler flowmetry (LDF), comprises capillary, arterial, and venous blood flow. With the classical LDF approach, it has been impossible to differentiate between different vascular compartments. We suggest an alternative LDF algorithm that estimates at least three concentration measures of flowing red blood cells (RBCs), each associated with a predefined, physiologically relevant, absolute velocity in millimeters per second. As the RBC flow velocity depends on the dimension of the blood vessel, this approach might enable a microcirculatory flow differentiation. The LDF concentration estimates are derived by fitting predefined Monte Carlo simulated, single-velocity spectra to a measured, multiple-velocity LDF spectrum. Validation measurements, using both single- and double-tube flow phantoms perfused with a microsphere solution, show that it is possible to estimate velocity and concentration changes, and to differentiate between flows with different velocities. Our theory is also applied to RBC flow measurements. A Gegenbauer kernel phase function (alpha(gk)=1.05; g(gk)=0.93), with an anisotropy factor of 0.987 at 786 nm, is found suitable for modeling Doppler scattering by RBCs diluted in physiological saline. The method is developed for low concentrations of RBCs, but can in theory be extended to cover multiple Doppler scattering.

Algorithms↗