Biomedical subjects

L Karlsson

Publications and source records attributed to L Karlsson.

At least 19 recordsLinked to original sources

PubMed2006

Time components of circulatory transport from the lungs to a peripheral artery in humans.

Blood gas changes occurring in the lung undergo delay and damping on their way to a peripheral artery sampling site. Knowledge of the time components of circulatory transfer is important for the understanding of respiratory control and cardiovascular reflexes in response to blood gas transients. Providing steady state with regard to VA/Q distribution, cardiac output and peripheral blood flow, the relationship between the time courses of small end-tidal and peripheral PO2 changes is determined by the transfer function of the interposed vascular segment. This transfer function, expressed as delay time TD and mean transit time (MTT), was measured in six well-trained subjects, allowing the calculation of arterial time-courses from end-tidal to the reverse. They were studied at rest and during four different dynamic leg exercise intensities in the supine posture. TD and MTT amounted to 15.8 +/- 1.7 (mean +/- SEM) and 18.3 +/- 2.1 s at rest and were shortened to 7.7 +/- 0.6 and 11.5 +/- 1.8 s during exercise at 170 W. The shortening of TD and MTT did not appear to be simply an inverse function of cardiac output, suggesting that the shortening occurs in the central circulatory segment but not in the arm segment.

Adult↗

PubMed2006

Lead and cadmium in meat and meat products consumed by the population in Tenerife Island, Spain.

The aim of this study was to determine the levels of lead and cadmium in chicken, pork, beef, lamb and turkey samples (both meat and meat products), collected in the island of Tenerife (Spain). Lead and cadmium were measured by graphite furnace atomic absorption spectrometry (GFAAS). Mean concentrations of lead and cadmium were 6.94 and 1.68 microg kg(-1) in chicken meat, 5.00 and 5.49 microg kg(-1) in pork meat, 1.91 and 1.90 microg kg(-1) in beef meat and 1.35 and 1.22 microg kg(-1) in lamb meat samples, respectively. Lead was below the detection limit in turkey samples and mean cadmium concentration was 5.49 microg kg(-1). Mean concentrations of lead and cadmium in chicken meat product samples were 3.16 and 4.15 microg kg(-1), 4.89 and 6.50 microg kg(-1) in pork meat product, 6.72 and 4.76 microg kg(-1) in beef meat product and 9.12 and 5.98 microg kg(-1) in turkey meat product samples, respectively. The percentage contribution of the two considered metals to provisional tolerable weekly intake (PTWI) was calculated for meat and meat products. Statistically significant differences were found for lead content in meats between the chicken and pork groups and the turkey and beef groups, whereas for cadmium concentrations in meats, significant differences were observed between the turkey and chicken, beef and lamb groups. In meat products, no clear differences were observed for lead and cadmium between the various groups.

Animals↗

PubMed2006

TNF-alpha mediated suppression of tissue type plasminogen activator expression in vascular endothelial cells is NF-kappaB- and p38 MAPK-dependent.

BACKGROUND: Several proatherothrombotic conditions are associated with enhanced levels of circulating proinflammatory cytokines, which are believed to impair endothelial fibrinolytic capacity. OBJECTIVE: This study aims at investigating how tumor necrosis factor (TNF)-alpha regulates endothelial gene expression of the key fibrinolytic enzyme tissue-type plasminogen activator (t-PA). METHODS: Cultured human umbilical vein endothelial cells were pretreated with selective inhibitors of the three major inflammatory signaling pathways activated by TNF-alpha; the nuclear factor kappa-B (NF-kappaB), the p38 mitogen-activated protein kinase (p38 MAPK), and the c-jun N-terminal kinase (JNK) pathways. Following TNF-alpha stimulation, effects on t-PA gene expression were evaluated with real-time reverse transcriptase polymerase chain reaction and interactions of nuclear proteins with potential gene regulatory elements were studied with electrophoretic mobility shift assays. RESULTS: Approximately 50% suppression of t-PA gene expression was observed after prolonged stimulation with TNF-alpha (> or =24 h). The repression was shown to be preferentially dependent on NF-kappaB activation, but also on p38 MAPK signaling. Further, we provide evidence for a TNF-alpha induced binding of NF-kappaB to the recently described kappaB site in the t-PA gene and of cyclic adenosine monophosphate response element binding protein (CREB) to the t-PA CRE-like site. CONCLUSIONS: We conclude that TNF-alpha impairs fibrinolytic capacity in vascular endothelial cells by a NF-kappaB and p38 MAPK-dependent suppression of t-PA. This mechanism sheds a light on how inflammation contributes to the pathogenesis of cardiovascular diseases.

Binding Sites↗

PubMed2005

Angular distribution of different vibrational components of the X and B states reached after resonant Auger decay of core-excited H2O: experiment and theory.

Vibrationally resolved spectra have been obtained for the lowest-lying cationic states X (2)B(1), A (2)A(1), and B (2)B(2) of the water molecule reached after participator resonant Auger decay of core-excited states. The angular distribution has been measured of the first four vibrational components of the X state in the photon energy regions including the O 1s-->4a(1) and the O 1s-->2b(2) core excitations, and for different portions of the vibrational envelope of the B state in the photon energy region including the O 1s-->2b(2) core excitation. For the X state, a large relative spread in beta values of the different vibrational components is observed across both resonances. For the B state, a very different trend is observed for the high binding energy side and the low binding energy side of the related spectral feature as a function of photon energy. A theoretical method based on the scattering K matrix has been used to calculate both the photoabsorption spectrum and the beta values, by taking both interference between direct and resonant photoemission and vibrational/lifetime interference into account. The numerical results show qualitative agreement with the trends detected in the experimental values and explain the conspicuous variations of the beta values primarily in terms of coupling between direct and resonant photoemission by interaction terms of different sign for different final vibrational states.

Journal Article↗

PubMed2005

Relation between blood- and urine-amphetamine concentrations in impaired drivers as influenced by urinary pH and creatinine.

Amphetamine undergoes extensive renal excretion and significant amounts are present in urine as the unchanged parent drug. This prompted us to investigate whether a quantitative relationship existed between blood and urine concentrations of amphetamine in the body fluids of drug-impaired drivers apprehended in Sweden, where this stimulant is the major drug of abuse. The relationship between blood and urine concentrations of amphetamine was determined by multivariate analysis with urinary pH and creatinine as predictor variables. Amphetamine was determined in blood and urine by gas chromatography-mass spectrometry with deuterium-labelled internal standards. The concentration of amphetamine in urine was about 200 times greater than the concentration in blood; the mean and median urine/blood ratios were 214 and 160, respectively, with large individual variations. The Pearson correlation coefficient between urine (y) and blood (x) amphetamine was r = 0.53, n = 48, which was statistically highly significant (P < 0.001), although the residual standard deviation (SD) was large (+/- 181 mg/L). The correlation coefficient increased (r = 0.60) when the concentration of amphetamine in urine was normalized for dilution by dividing with the creatinine content. When urinary pH and creatinine were both included as predictor variables, the correlation coefficient was even higher (r = 0.69), now explaining 48% (r2 = 0.48) of the variation in urine-amphetamine concentration. However, the partial regression coefficient for creatinine (53 +/- 28.7) was not statistically significant (t = 1.85, P > 0.05), whereas the corresponding regression coefficient for pH was highly significant and had a negative sign (-102 +/- 32.6, t= -3.12, P < 0.005). Other factors could impact on the urine-blood amphetamine relationship, such as route of administration, pattern of voiding and time elapsed after use of the drug.

Adult↗

PubMed2004

Mobilized blood cells vs bone marrow harvest: experience compared in 171 donors with particular reference to pain and fatigue.

This prospective study compared the donor experience of blood cell (BC) mobilization and leukapheresis (n=116) with that of bone marrow (BM) harvest (n=55). Internal jugular catheters were inserted electively in 89% of BC donors. Most (80%) BM donors had a harvest with general anesthesia; 20% had epidural or spinal anesthesia. Pain and fatigue were frequent with both procedures and were compared in responses to questionnaires. A total of 85% of BM donors reported moderate or severe pain compared with 68% of BC donors (P=0.02). The median duration of pain was 14 days for BM donors compared with 3 days after BC mobilization (P<0.0001). More BM donors had pain for more than 7 days (75% vs 0%, P<0.0001). Severe fatigue was experienced by more BM donors (49 vs 16%, P<0.0001). Fatigue lasted significantly longer in BM donors (median 11 vs 4 days, P<0.0001) and more BM donors were fatigued for more than 1 week (69 vs 0%, P<0.0001). A total of 11 donors had both BM and BC collection; seven preferred the latter. Simply considered with respect to pain and fatigue, BC donation appears better tolerated by donors. However, there are other sequelae of both influencing the acceptability for individual donors.

Adolescent↗

PubMed2003

Activity and protein expression of Na+/K+ ATPase are reduced in microvillous syncytiotrophoblast plasma membranes isolated from pregnancies complicated by intrauterine growth restriction.

In contrast to classical transporting epithelia, the Na(+)/K(+) ATPase is distributed to both the microvillous membrane (MVM) and the basal membrane (BM) of the placental syncytiotrophoblast. Na(+)/K(+) ATPase is important in maintaining the electrochemical gradient for Na(+), which represents the driving force for Na(+)-coupled transport of nutrients. We hypothesized that syncytiotrophoblast Na(+)/K(+)-ATPase activity is reduced in intrauterine growth restriction (IUGR). We isolated MVM and BM from control (n = 10) and IUGR placentas (n = 11). The protein expression of Na(+)/K(+)-ATPase alpha(1)-subunit was determined by Western blotting and found to be slightly reduced in MVM isolated from IUGR (-10%; P < 0.05) placentas. Na(+)/K(+) ATPase activity was measured as the ouabain-sensitive, K(+)-dependent cleavage of the fluorescent pseudosubstrate 3-O-methylfluorescein phosphate and was reduced by 35% in MVM obtained from IUGR placentas (P < 0.02). To assess the transcriptional levels of Na(+)/K(+)-ATPase mRNA, real time PCR was used. No significant changes in steady state mRNA levels for Na(+)/K(+)-ATPase were detected. The expression of the Na(+)/K(+)-ATPase alpha(1)-subunit and Na(+)/K(+)-ATPase activity in the BM were unaffected in cases of IUGR. These data suggest that Na(+)/K(+)-ATPase activity is reduced in the MVM of placentas from IUGR pregnancies. These changes might impair the function of Na(+)-coupled transporters and contribute to the reduced growth of these fetuses.

Case-Control Studies↗

PubMed2002

Interference quenching of nu(")=1 vibrational line in resonant photoemission of N2: a possibility to obtain geometrical information on the core-excited state.

An interference quenching of the nu(")=1 vibrational line in the resonant Auger decay of N 1s-->pi(*) core-excited N2 is observed and analyzed. The intensity ratio between the nu(")=1 and nu(")=0 vibrational levels of the X2Sigma(+)(g) final state shows a surprising nonmonotonous variation as a function of frequency detuning, going through a minimum with a complete suppression of nu(")=1. We have developed a simple model which shows a linear relation between the value of the detuning frequency for this minimum and the equilibrium bond distance R(0)(c) of the core-excited state. A new way is thus established of determining the equilibrium bond distance for the core-excited state with a precision deltaR(0)(c)<10(-3) A.

Journal Article↗

PubMed2001

The impact of H2-DM on humoral immune responses.

H2-DM (DM, previously H2-M) facilitates the exchange of peptides bound to MHC class II molecules. In this study, we have used H2-DM-deficient (DM(-/-)) mice to analyze the influence of DM in the priming of B cell responses in vivo and for Ag presentation by B cells in vitro. After immunization, IgG Abs could be raised to a T-dependent Ag, 4-hydroxy-5-nitrophenylacetyl-OVA, in DM(-/-) mice, but closer analysis revealed the IgG response to be slower, diminished in titer, and composed of low-affinity Abs. The Ab response correlated with a vast reduction in the number of germinal centers in the spleen. The presentation of multiple epitopes by H2-A(b) from distinct Ags was found to be almost exclusively DM-dependent whether B cells internalized Ags via fluid phase uptake or using membrane Ig receptors. The poor B cell response in vivo could be largely, but not completely restored by expression of a H2-Ea(d) transgene, despite the fact that Ag presentation by H2-E(d/b) molecules was found to be highly DM dependent. Hence, while substantial Ab responses can be raised in the absence of DM, this molecule is a crucial factor both for Ag processing and for the normal maturation of T-dependent humoral immune responses in vivo.

Animals↗

PubMed2001

Defective antigen processing in GILT-free mice.

Processing of proteins for major histocompatibility complex (MHC) class II-restricted presentation to CD4-positive T lymphocytes occurs after they are internalized by antigen-presenting cells (APCs). Antigenic proteins frequently contain disulfide bonds, and their reduction in the endocytic pathway facilitates processing. In humans, a gamma interferon-inducible lysosomal thiol reductase (GILT) is constitutively present in late endocytic compartments of APCs. Here, we identified the mouse homolog of GILT and generated a GILT knockout mouse. GILT facilitated the processing and presentation to antigen-specific T cells of protein antigens containing disulfide bonds. The response to hen egg lysozyme, a model antigen with a compact structure containing four disulfide bonds, was examined in detail.

Amino Acid Sequence↗

PubMed2001

A large family of endosome-localized proteins related to sorting nexin 1.

Sorting nexin 1 (SNX1), a peripheral membrane protein, has previously been shown to regulate the cell-surface expression of the human epidermal growth factor receptor [Kurten, Cadena and Gill (1996) Science 272, 1008-1010]. Searches of human expressed sequence tag databases with SNX1 revealed eleven related human cDNA sequences, termed SNX2 to SNX12, eight of them novel. Analysis of SNX1-related sequences in the Saccharomyces cerevisiae genome clearly shows a greatly expanded SNX family in humans in comparison with yeast. On the basis of the predicted protein sequences, all members of this family of hydrophilic molecules contain a conserved 70-110-residue Phox homology (PX) domain, referred to as the SNX-PX domain. Within the SNX family, subgroups were identified on the basis of the sequence similarities of the SNX-PX domain and the overall domain structure of each protein. The members of one subgroup, which includes human SNX1, SNX2, SNX4, SNX5 and SNX6 and the yeast Vps5p and YJL036W, all contain coiled-coil regions within their large C-terminal domains and are found distributed in both membrane and cytosolic fractions, typical of hydrophilic peripheral membrane proteins. Localization of the human SNX1 subgroup members in HeLa cells transfected with the full-length cDNA species revealed a similar intracellular distribution that in all cases overlapped substantially with the early endosome marker, early endosome autoantigen 1. The intracellular localization of deletion mutants and fusions with green fluorescent protein showed that the C-terminal regions of SNX1 and SNX5 are responsible for their endosomal localization. On the basis of these results, the functions of these SNX molecules are likely to be unique to endosomes, mediated in part by interactions with SNX-specific C-terminal sequences and membrane-associated determinants.

Amino Acid Sequence↗

PubMed2001

On-line process control of liquid chromatography.

Many analytical methods are based on liquid chromatography and typically the only measure of system stability is standards, injected repeatedly throughout the sequence. In this paper, a novel approach is presented, where the analytical run is treated as a process with the chromatographic data as the product. It is postulated that enhanced quality of the data can be obtained through monitoring the process, i.e., the chromatographic system, during the sequence. For this purpose, a liquid chromatography process control (LCPC) system has been developed. Here, several parameters, e.g., the pressure at the column and the injection valve, are monitored. Chemometrics is used for interpreting the data and producing multivariate statistical process control (MSPC) charts. The chromatographic run is divided into two parts: the dynamic injection phase and the static elution phase. Two principal component analysis (PCA) models, one for each phase, are continuously created and upgraded as the data are collected. The results of the PCA are shown in the MSPC charts, and when an error detection limit is exceeded, the analyst is promptly notified. LCPC, a continuous system suitability test, provides better control of the analysis, allowing a reduction in the number of standards and replicates. Furthermore, troubleshooting is facilitated.

Journal Article↗

PubMed2001

Costimulation via lymphocyte function-associated antigen 1 in the absence of CD28 ligation promotes anergy of naive CD4+ T cells.

The mechanisms controlling induction of anergy at the level of naive CD4+ T cells are poorly understood but thought to reflect limited contact with costimulatory molecules during T cell antigen receptor (TCR) ligation. To clarify this question, naive TCR transgenic CD4+ cells were exposed to specific peptide presented by transfected antigen-presenting cells (APC) expressing MHC class II molecules with defined accessory molecules. Significantly, culturing CD4(+) cells with APC expressing MHC II plus peptide alone elicited early TCR signaling but failed to induce either proliferation or anergy. Culture with APC expressing MHC II plus B7 molecules led to strong proliferation and T cell priming but no anergy. In marked contrast, conspicuous induction of anergy occurred after T cell culture with APC expressing MHC class II and intercellular adhesion molecule-1 (ICAM-1). Thus, at the level of naive CD4(+) cells, anergy induction appears to reflect selective contact with APC expressing ICAM-1 in the absence of B7.

Animals↗

PubMed2001

KIR down-regulation on NK cells is associated with down-regulation of activating receptors and NK cell inactivation.

We previously reported that killer cell immunoglobulin-like receptors (KIR) could be down-regulated from the surface of T cells. Here, we show that KIR down-regulation is also induced on the surface of natural killer (NK) cells upon ligand binding. Common down-regulation characteristics are found on these two cell types: a slow kinetics and a phenomenon observed for long inhibitory forms only. Importantly, KIR down-regulation on NK cells is associated with a down-regulation of activating receptors (CD16, CD2 and 2B4) as well as with a lack of cell responsiveness (antibody-dependent and natural killing activities). This unresponsive state was not observed for MHC-restricted T cells. Our data implicate that, in addition to prevention of the immediate target cell lysis, KIR-MHC class I interactions may also regulate the subsequent NK cell cytotoxic activity. This observation opens new perspectives in the understanding of NK cell regulation.

Animals↗

PubMed2001

Developmental roles of platelet-derived growth factors.

Platelet-derived growth factor (PDGF) was originally identified in platelets and in serum as a mitogen for fibroblasts, smooth muscle cells (SMC) and glia cells in culture. PDGF has since expanded to a family of dimers of at least four gene products, whose biological actions are mediated through two receptor tyrosine kinases, PDGFRs. The present review summarizes and discusses the biological functions of PDGFs and PDGFRs in developmental processes, mainly as revealed through genetic analysis in mice. Such studies have demonstrated multiple critical roles of PDGFs and PDGFRs in embryonic and postnatal development. PDGFs seem to act upon specific populations of progenitor cells that give rise to several different cell types with distinct functions in a variety of developmental processes. Analogies are seen between the cell functions and the developmental processes controlled by PDGFs. This suggests that ancestral PDGF and PDGFR expression patterns and functions may have been iterated in related sets of morphogenetic processes in the course of evolution.

Aging↗

PubMed2001

Simulation of the normal concentric needle electromyogram by using a muscle model.

OBJECTIVES: To study the correlation between anatomical parameters and EMG signals by means of simulations. METHODS: A mathematical model of the electrical activity from muscle fibres and motor units has been developed. The electrical fields around the muscle fibres are simulated using a line source model. The model permits the simulation of single muscle fibre action potentials obtained by SFEMG, concentric and Macro EMG electrodes. By using appropriate anatomical parameters EMG recordings with these electrodes can be simulated. The model is flexible and permits a number of anatomical parameters to be changed such as; number of muscle fibres in a motor unit, fibre diameter distribution, and motor end-plate geometry. Some physiological parameters can be optionally varied; firing rate, threshold for recruitment, jitter. RESULTS: In this study, simulations of CNEMG are performed and the influence of a number of parameters on the CNEMG signal is studied. It is shown that the model produces motor unit potentials reasonably well resembling those from live recordings. More important is however the relative change in MUP parameters when certain conditions are changed; number of muscle fibres in a motor unit, recording position, muscle fibre diameters and some special effects of the recording conditions. CONCLUSIONS: The simulated muscle and corresponding EMG recording can be used both as a research tool and for teaching.

Electrodes↗

PubMed2001

Simulation of EMG in pathological situations.

OBJECTIVE: A mathematical model for simulation of the EMG from a muscle with its motor units is used. The study aims at correlating EMG findings (single-fiber EMG and concentric-needle EMG) with various induced morphological changes. METHODS: Reinnervation has been simulated by removing motor units randomly followed by a complete reinnervation from adjacent surviving motor units. Fibre type grouping and grouped atrophy can be seen. Myopathy is simulated by increased fibre diameter variation, loss of fibres and muscle fibre splitting. RESULTS AND CONCLUSION: The simulation gives quantitative aspects of the importance of each of these factors. It indicates the relative sensitivity of various EMG parameters. The model can be used both for education and for research.

Action Potentials↗

PubMed2001

The motor nerve simulator.

OBJECTIVE: The aim of the study was to develop a mathematical model of the motor nerve and the action potentials generated from its axons, in order to simulate conditions seen in neurography. The model should be used for the detailed study of the relationship between various nerve characteristics and the electrophysiological recordings obtained. METHODS: The model was developed as a software tool. The signals from individual motor units were real recordings using conventional surface electrodes. There was good agreement between the constructed compound muscle action potential and the one recorded live for the subject from whom the individual signals were obtained. RESULT: A number of physiological characteristics can be changed, including the number of axons, their conduction properties, excitability properties, degree of proximo-distal velocity slowing. F-waves and A-waves can be generated. CONCLUSION: The model gives a good similarity to findings obtained in live recordings. A number of physiological characteristics can be studied individually, something that cannot be done in live recordings. The model can be used in teaching and in research studies of the relationship between nerve properties and neurography parameters.

Action Potentials↗