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Biomedical subjects

M Persson

Publications and source records attributed to M Persson.

At least 19 recordsLinked to original sources

Femtosecond laser induced associative desorption of H2 from Ru(0001): comparison of "first principles" theory with experiment.

A three dimensional model based on molecular dynamics with electronic frictions is developed to describe the femtosecond laser induced associative desorption of H2 from Ru(0001)(1 x 1)H. Two molecular coordinates (internuclear separation d and center of mass distance to surface z) and a single phonon coordinate are included in the dynamics. Both the potential energy surface and the electronic friction tensor are calculated by density functional theory so that there are no adjustable parameters in the comparison of this model with the wide range of experiments available for this system. This "first principles" dynamic model gives results in semiquantitative agreement with all experimental results; nonlinear fluence dependence of the yield, isotope effect, two pulse correlation, and energy partitioning. The good agreement of theory with experiment supports a description of this surface femtochemistry in terms of thermalized hot electron induced chemistry with coupling to nuclear coordinates through electronic frictions. By comparing the dynamics with the analytical one dimensional frictional model used previously to fit the experiments for this system, we show that the success of the one dimensional model is based on the rapid intermixing of the z and d coordinates as the H-H climbs out of the adsorption well. However, projecting the three dimensional dynamics onto one dimension introduces a fluence (adsorbate temperature) dependent "entropic" barrier in addition to the potential barrier for the chemistry. This implies that some caution must be used in interpreting activation energies obtained in fitting experiments to the one dimensional model.

Journal Article↗

Theoretical evidence for nonadiabatic vibrational deexcitation in H2(D2) state-to-state scattering from Cu(100).

Dynamical calculations are presented for electronically nonadiabatic vibrational deexcitation of H2 and D2 in scattering from Cu(111). Both the potential energy surface and the nonadiabatic coupling strength were obtained from density functional calculations. The theoretically predicted magnitude of the deexcitation and its dependence on incident energy and isotope are all in agreement with state-to-state scattering experiments [on Cu(100)], and this gives indirect evidence for a nonadiabatic mechanism of the observed deexcitation. Direct evidence could be obtained by measuring the chemicurrent associated with the deexcitation, and its properties have been predicted.

Journal Article↗

Corticosterone inhibits expression of the microglial glutamate transporter GLT-1 in vitro.

The present study investigates the effect of the glucocorticoid corticosterone on microglial glutamate transporters in vitro. Microglial cultures obtained from rat cerebral cortex were found to express the excitatory amino acid transporter GLT-1, but not GLAST, and this expression was increased by 1 ng/ml lipopolysaccharide after 12 h of stimulation. This increase has previously been shown to be mediated by tumor necrosis factor-alpha, a cytokine released by microglia during pathological conditions. Furthermore, lipopolysaccharide increased the microglial release of tumor necrosis factor-alpha and 1 microM corticosterone inhibited this effect. Corticosterone also inhibited the lipopolysaccharide-induced increase of the GLT-1 expression as well as the expression in non-activated cells. The effect of corticosterone on the GLT-1 expression was dose dependent and accompanied by similar effects on the microglial glutamate uptake capacity. Additionally, exogenous tumor necrosis factor-alpha was found to counteract the effect of corticosterone on microglial GLT-1 expression. The effect of corticosterone appeared to be glucocorticoid receptor specific since 10 microM of the glucocorticoid receptor antagonist mifepristone inhibited the effect. Thus, corticosterone decreased the microglial uptake of glutamate by decreasing the expression of glutamate transporters, probably due to the inhibited microglial tumor necrosis factor-alpha release. These results provide insights into the mechanisms behind microglial glutamate transporter expression during pathological conditions, and contribute to the debate about the beneficial or harmful effects of glucocorticoids.

Analysis of Variance↗

Planning for intracavitary anti-EGFR radionuclide therapy of gliomas. Literature review and data on EGFR expression.

Targeting with radionuclide labelled substances that bind specifically to the epidermal growth factor receptor, EGFR, is considered for intracavitary therapy of EGFR-positive glioblastoma multiforme, GBM. Relevant literature is reviewed and examples of EGFR expression in GBM are given. The therapeutical efforts made so far using intracavitary anti-tenascin radionuclide therapy of GBM have given limited effects, probably due to low radiation doses to the migrating glioma cells in the brain. Low radiation doses might be due to limited penetration of the targeting agents or heterogeneity in the expression of the target structure. In this article we focus on the possibilities to target EGFR on the tumour cells instead of an extracellular matrix component. There seems to be a lack of knowledge on the degree of intratumoral variation of EGFR expression in GBM, although the expression seemed rather homogeneous over large areas in most of the examples (n=16) presented from our laboratory. The observed homogeneity was surprising considering the genomic instability and heterogeneity that generally characterises highly malignant tumours. However, overexpression of EGFR is, at least in primary GBMs, one of the steps in the development of malignancy, and tumour cells that lose or downregulate EGFR will probably be outgrown in an expanding tumour cell population. Thus, loss of EGFR expression might not be the critical factor for successful intracavitary radionuclide therapy. Instead, it is likely that the penetration properties of the targeting agents are critical, and detailed studies on this are urgent.

Antibodies↗

Situations influencing habits in diet and exercise among nurses working night shift.

OBJECTIVES: The aim of the investigation was to describe situations with a significant influence on healthy diet and exercise habits among nurses working night shift. METHODS: A qualitative descriptive design with a Critical Incident Technique approach was used. Situations were collected by means of interviews with 27 registered/enrolled community nurses. RESULTS: A total of 143 situations were identified comprising two main areas: coping ability at work and coping ability during leisure hours. Coping ability at work included 81 critical incidents grouped into two categories: the nurses' diet and exercise habits were influenced by social interaction with colleagues at work and by the disruption to their circadian rhythm. Coping ability during leisure hours included 62 critical incidents grouped into two categories: the diet and exercise habits were influenced when the nurses recovered from the disruption to their circadian rhythm and when they took advantage of the freedom of action offered by night work. CONCLUSIONS: By identifying the factors that influence diet and exercise habits among nurses working night shift, strategies can be developed in order to strengthen the factors with a positive influence.

Adaptation, Psychological↗

How adiabatic is activated adsorption/associative desorption?

Using density-functional theory we calculate friction coefficients describing the damping of nuclear motion into electron-hole pair excitation for the two best-known examples of activated adsorption: H2 dissociation on a Cu(111) surface and N2 dissociation on a Ru(0001) surface. In both cases, the frictions increase dramatically along the reaction path towards the transition state and can be an order of magnitude larger there than typical in the molecularly adsorbed state. In addition, the frictions for N2/Ru(0001) are typically an order of magnitude larger than for H2/Cu(111). We rationalize these trends in terms of the electron structure as the systems proceed to dissociation along the reaction paths. Combining these friction coefficients with the potential-energy surface in quasiclassical dynamics allows first-principles studies of the importance of the breakdown in the Born-Oppenheimer approximation in describing the chemistry. We find that nonadiabatic effects are minimal for the H2/Cu(111) system, but are quite important for N2/Ru(0001).

Journal Article↗

In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for treatment of head and neck squamous cell carcinoma.

PURPOSE: The purpose of this study was to analyse the properties of the astatinated chimeric MAb (cMAb) U36 as a conjugate to selectively target and eradicate head and neck squamous cell carcinoma (HNSCC). METHODS: cMAb U36 was labelled with 211At via the linker N-succinimidyl 4-(trimethylstannyl)benzoate (SPMB). The quality of the conjugate was extensively evaluated for binding and internalisation capacity, and compared with 125I-SPMB-cMAb U36. The cellular toxicity of the astatinated conjugate was assessed in two types of in vitro growth assay and compared with 131I-labelled cMAb U36 (directly labelled). RESULTS: Comparisons between 211At-cMAb U36 and 125I-cMAb U36 demonstrated an optimal functional capacity of the labelled products. Immunoreactivity and affinity assays showed high immunoreactive fractions (>93%), and an affinity in good agreement between the astatinated and iodinated antibodies. For both conjugates, specific binding to HNSCC cells could be demonstrated, as well as some internalisation. Retention of the astatinated conjugate was just slightly lower than for the iodinated conjugate and still reasonable for therapeutic use (31+/-2% vs 42.6+/-1.0% at 22 h), demonstrating no adverse effects from astatination of the antibody. Studies on cellular toxicity demonstrated a dose-dependent and antigen-specific cellular toxicity for 211At-cMAb U36, with about 10% cell survival at 50 decays per cell. The 131I-labelled conjugate was not as efficient, with a surviving cell fraction of about 50% at 55 decays per cell. CONCLUSION: These results indicate that 211At-cMAb U36 might be a promising future candidate for eradicating HNSCC micrometastases in vivo.

Antibodies, Monoclonal↗

Electronic nonadiabatic effects in the adsorption of hydrogen atoms on metals.

The time-dependent, mean-field Newns-Anderson model for a spin-polarized adsorbate approaching a metallic surface is solved in the wide-band limit. Equations for the time evolution of the occupation of the spin dependent adsorbate states and for the nonadiabatic and nearly adiabatic adsorbate-surface energy transfer rates are derived. Numerical solutions are obtained using characteristic parameters derived from density functional theory calculations for the H/Cu(111) system. The time evolution of the model system is shown to be strongly nonadiabatic in the vicinity of the transition point between spin-polarized and nonpolarized ground states. Away from the spin transition the nonadiabatic energy transfer is in close agreement with the nearly adiabatic limit. Near the transition, nonadiabatic effects are large and the nearly adiabatic approximation fails.

Journal Article↗

Cell-type-specific expression of p53 and p21 in giant cell arteritis.

The aim of the present study was to investigate the expression of TP53 (p53) and CDKN1A (CIP1; p21) in the arterial wall in giant cell arteritis (GCA). Cross-sections from 18 temporal artery biopsies displaying GCA and 8 control arteries were double-stained with monoclonal antibody directed at p53 or p21 on the one hand and alpha-smooth muscle actin, CD68 (macrophage) or CD3 (T-cell) on the other. Nuclear p53 was expressed in CD68-positive cells and smooth muscle cells in 16 of the 18 inflamed arteries. P21-positive nuclei were found in CD68-positive cells in 14 biopsies and in smooth muscle cells in all the specimens. All p53-positive giant cells also contained p21-positive nuclei. In the giant cells, immunopositive nuclei were mixed with negative ones. CD3-positive T-cells did not express p53 or p21. Only one p53-positive smooth muscle cell nucleus was found in the non-GCA controls and, compared with GCA, p21 expression was noted in few smooth muscle nuclei. The presence of p53 and p21 in the same types of cell in GCA indicates that the former protein is functional; p21 expression is induced by wild-type, functional p53 but not by its mutant form. The current observations suggest cellular stress in GCA, the nature of which requires further investigation.

Aged↗

Carbon dioxide inhibits the growth rate of Staphylococcus aureus at body temperature.

BACKGROUND: Since the 1930s, carbon dioxide (CO(2)) has been combined with cold storage for the preservation of food. However, its use for the prevention of surgical wound infection was long considered to be impractical. Now CO(2) is widely used during laparoscopic procedures, and a method has been developed to create a CO(2) atmosphere in an open wound. The aim of this study was to investigate the effect of CO(2) on the growth of Staphylococcus aureus at body temperature. METHODS: First, S. aureus inoculated on blood agar were exposed to pure CO(2) (100%), standard anaerobic gas (5% CO(2), 10% hydrogen, 85% nitrogen), or air at 37 degrees C for a period of 24 h; then a viable count of the bacteria was made. Second, S. aureus inoculated in brain-heart infusion broth and kept at 37 degrees C were exposed to CO(2) or air for 0, 2, 4, 6, and 8 h; then the optical density of the bacteria was measured. RESULTS: After 24 h, the number of S. aureus on blood agar was about 100 times lower in CO(2) than in anaerobic gas (p = 0.001) and about 1,000 times lower than in air (p = 0.001). Also, in broth, there were fewer bacteria with CO(2) than with air (p < 0.01). After 2 h, the number of bacteria was increased with air (p < 0.001) but not with CO(2) (p = 0.13). After 8 h, the optical density had increased from zero to 1.2 with air but it had increased only to 0.01 with CO(2) (p = 0.001). CONCLUSION: Pure CO(2) significantly decreased the growth rate of S. aureus at body temperature. The inhibitory effect of CO(2) increased exponentially with time. Its bacteriostatic effect may help to explain the low infection rates in patients who undergo laparoscopic procedures.

Body Temperature↗

Localization of the Cu111 surface state by single Cu adatoms.

The Cu adatom-induced localization of the two-dimensional Shockley surface state at the Cu(111) surface was identified from experimental and simulated scanning tunneling microscopy spectra. The localization gives rise to a resonance located just below the surface state band edge. The adatom-induced surface state localization is discussed in terms of the existence theorem for bound states in any attractive two-dimensional potential. We also identify adatom-induced resonance states deriving from atomic orbitals in both experimental and simulated spectra.

Journal Article↗

Spin splitting of s and p states in single atoms and magnetic coupling in dimers on a surface.

Electronic states of magnetic atoms (Mn, Fe, and Co) and artificially assembled dimers (Mn2, Fe2, and Co2) on a NiAl(110) surface were probed by scanning tunneling spectroscopy at 17 K. Resonance peaks characteristic of each adsorbed species were observed in the unoccupied density of states. Comparison of the measured spectra with calculations by density functional theory revealed spin splitting in the unoccupied states with s and p characters for the single magnetic adatoms and addimers. The magnitude of the resonance splitting for the adatoms increased with the calculated values of magnetic moments. The resonance structures for the addimers exhibited signatures of their internal magnetic coupling.

Journal Article↗

Effect of CO2 insufflation on the number and behavior of air microemboli in open-heart surgery: a randomized clinical trial.

BACKGROUND: The risks that the presence of air microemboli implies in open-heart surgery have recently been emphasized by reports that their number is correlated with the degree of postoperative neuropsychological disorder. Therefore, we studied the effect of CO2 insufflation into the cardiothoracic wound on the incidence and behavior of microemboli in the heart and ascending aorta. METHODS AND RESULTS: Twenty patients undergoing single-valve surgery were randomly divided into 2 groups. Ten patients were insufflated with CO2 via a gas diffuser, and 10 were not. Microemboli were ascertained by intraoperative transesophageal echocardiography (TEE) and recorded on videotape from the moment that the aortic cross-clamp was released until 20 minutes after end of cardiopulmonary bypass (CPB). The surgeon performed standard de-airing maneuvers without being aware of TEE findings. Postoperatively, a blinded assessor determined the maximal number of gas emboli during each consecutive minute in the left atrium, left ventricle, and ascending aorta. The 2 groups did not differ in the usual clinical parameters. The median number of microemboli registered during the whole study period was 161 in the CO2 group versus 723 in the control group (P<0.001). Corresponding numbers for the left atrium were 69 versus 340 (P<0.001), left ventricle 68 versus 254 (P<0.001), and ascending aorta 56 versus 185 (P<0.001). In the CO2 group, the median number of detectable microemboli after CPB fell to zero 7 minutes after CPB versus 19 minutes in the control group (P<0.001). CONCLUSIONS: Insufflation of CO2 into the thoracic wound markedly decreases the incidence of microemboli.

Aged↗

Validation of fractional moving blood volume measurement with power Doppler ultrasound in an experimental sheep model.

OBJECTIVE: To compare fractional moving blood volume (FMBV) estimation using power Doppler ultrasound (PDU) with blood flow estimation using radioactive microspheres (RMS) for evaluation of fetal organ blood perfusion. METHODS: Blood flow was measured in the adrenal gland of nine exteriorized fetal lambs. Five fetal lambs underwent total umbilical cord occlusion in order to induce changes in the adrenal blood flow (asphyxia group). Four lambs were used as sham controls (control group). Three RMS injections, with coincident PDU recordings of the adrenal gland, were performed in each lamb. In the asphyxia group, measurements were taken before the cord occlusion, 5 min later and when the mean blood pressure decreased below 25 mmHg. In the control group, the measurements were done with an interval of 5 min. FMBV normalized for attenuation of PDU signals, and mean pixel intensity (MPI) were estimated offline. After completion of the study, adrenal blood perfusion was calculated according to the reference sample microsphere technique, using the isotope activity and expressed in mL/min/100 g. The correlation between RMS and FMBV and MPI, respectively, was analyzed individually for each lamb. RESULTS: In the asphyxia group, all lambs showed a marked reduction in the adrenal blood perfusion towards the third RMS injection. In the control group, the adrenal perfusion showed small variations throughout the experiment. In the total material, there was a higher correlation between FMBV and RMS (median, r = 0.90; range, 0.43-0.99) than between MPI and RMS (median, r = 0.55; range, -0.53 to 0.99). CONCLUSION: The FMBV method of quantifying PDU signals correlates highly with blood flow perfusion estimation using RMS in the fetal lamb adrenal gland.

Adrenal Glands↗

Wound ventilation with carbon dioxide: a simple method to prevent direct airborne contamination during cardiac surgery?

Carbon dioxide (CO2) insufflation in the cardiothoracic wound cavity is used in open-heart surgery for prevention of arterial air embolism. The objective of this study was to investigate if CO2 insufflation may influence the rate of airborne contamination of the cardiothoracic wound. This was studied in a cardiothoracic wound cavity model that contained two 9 cm blood agar plates. Contamination rates were compared between a control without insufflation and insufflation with: (1) a thin open-ended tube or a gas-diffuser, (2) air or CO2, and (3) CO2 flows of 5 or 10 L/min. CO2 insufflation at 5 L/min with an open-ended tube resulted in a contamination rate almost four times that of the control (P = 0.01), whereas with the gas-diffuser the contamination rate decreased (P = 0.01). With the gas-diffuser, air insufflation at 5 L/min markedly reduced the contamination rate compared with the control (P < 0.001), but was less protective than CO2 insufflation at the same flow (P < 0.001). With both gases, the contamination rate was particularly low close to the gas-diffuser (P < 0.001). Increasing the CO2 flow from 5 to 10 L/min reduced the average contamination rate in the model from 30% to 22% (P < 0.001) of the control. At a CO2 flow of 10 L/min the contamination rate within 9 cm of the gas-diffuser was 14% of the control. Intraoperative wound ventilation with CO2 using a gas-diffuser may not only prevent air embolism, but may also significantly reduce the risk of airborne contamination and postoperative wound infection in cardiac surgery. In contrast, insufflation with an open-ended tube substantially increases these risks.

Air Microbiology↗

Lameness in piglets. Abrasions in nursing piglets and transfer of protection towards infections with Streptococci from sow to offspring.

A group of 175 newborn piglets were monitored with respect to development of abrasions and lameness. Lameness was diagnosed in 10.9% of the piglets. About every second litter was affected and around 75% of these diagnoses took place during the first 3 weeks of life. Skin lesions were present already on day 3. They increased in magnitude until day 10 and thereafter declined. They were generally bilateral and most commonly observed as abrasions over the carpal joints. Hocks, face and tails were affected in a similar way, but at lower magnitudes. Sole bruising was observed in 87% of the piglets on the third day of life, and moderate to severe lesions dominated until day 10. Thereafter the incidence decreased, indicating healing with time. Still 39% of the piglets were affected at day 17. There was a significant positive correlation between skin lesions of carpus and hock within all examination days in selected piglets with known identity (n = 48). Between day 10 and 17 significant positive correlations were found within all examination sites with exception of abdomen and teats. The offspring of sows treated against mastitis expressed more abrasions then piglets delivered by healthy sows and the mortality during the first 17 days postpartum was significantly higher among piglets delivered by sows treated for mastitis. The level of serum antibodies to Streptococcus equisimilis in eight dams decreased during the last month of gestation and a declining maternal immunity to S. equisimilis was demonstrated in all piglets (n = 47) during the first 5 weeks of life. During the first 2 weeks of life somewhat lower median levels of serum antibodies were recorded among the piglets that were treated against arthritis (n = 8).

Animals↗

Mechanisms of molecular manipulation with the scanning tunneling microscope at room temperature: chlorobenzene/si(111)-(7 x 7).

We report a systematic experimental investigation of the mechanism of desorption of chlorobenzene molecules from the Si(111)-(7 x 7) surface induced by the STM at room temperature. We measure the desorption probability as a function of both tunneling current and a wide range of sample bias voltages between -3 V and +4 V. The results exclude field desorption, thermally induced desorption, and mechanical tip-surface effects. They indicate that desorption is driven by the population of negative (or positive) ion resonances of the chemisorbed molecule by the tunneling electrons (or holes). Density functional calculations suggest that these resonant states are associated with the pi orbitals of the benzene ring.

Journal Article↗

Distance dependence of the interaction between single atoms: gold dimers on NiAl(110).

The importance of substrate-mediated adsorbate-adsorbate interactions on electronic states has been demonstrated for Au dimers on NiAl(110) with a scanning tunneling microscope and density functional calculations. An unoccupied resonance observed in single Au atoms splits into a doublet in Au dimers. The energy splitting depends inversely on the distance between the two adatoms, revealing the relative importance of direct and substrate-mediated interactions. Spatially resolved conductance measurements of Au dimers reveal the symmetric and antisymmetric characters of the doublet states.

Journal Article↗