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Biomedical subjects

P Lundberg

Publications and source records attributed to P Lundberg.

At least 37 records · Page 2Linked to original sources
PubMed1997

The spatial dimension in population fluctuations

Theoretical research into the dynamics of coupled populations has suggested a rich ensemble of spatial structures that are created and maintained either by external disturbances or self-reinforcing interactions among the populations. Long-term data of the Canadian lynx from eight Canadian provinces display large-scale spatial synchrony in population fluctuations. The synchronous dynamics are not time-invariant, however, as pairs of populations that are initially in step may drift out of phase and back into phase. These observations are in agreement with predictions of a spatially-linked population model and support contemporary population ecology theory.

Journal Article↗
PubMed1997

Population dynamics and the colour of environmental noise.

The effect of red, white and blue environmental noise on discrete-time population dynamics is analyzed. The coloured noise is superimposed on Moran-Ricker and Maynard Smith dynamics, the resulting power spectra are less than examined. Time series dominated by short- and long-term fluctuations are said to be blue and red, respectively. In the stable range of the Moran-Ricker dynamics, environmental noise of any colour will make population dynamics red or blue depending the intrinsic growth rate. Thus, telling apart the colour of the noise from the colour of the population dynamics may not be possible. Population dynamics subjected to red and blue environmental noises show, respectively, more red or blue power spectra than those subjected to white noise. The sensitivity to differences in the noise colours decreases with increasing complexity and ultimately disappears in the chaotic range of the population dynamics. These findings are duplicated with the Maynard Smith model for high growth rates when the strength of density dependence changes. However, for low growth rates the power spectra of the population dynamics with noise are red in stable, periodic and aperiodic ranges irrespective of the noise colour. Since chaotic population fluctuations may show blue spectra in the deterministic case, this implies that blue deterministic chaos may become red under any colour of the noise.

Acoustics↗
PubMed1997

Diffusion of solutes in agarose and alginate gels: 1H and 23Na PFGSE and 23Na TQF NMR studies.

Cells immobilized in gels experience potential metabolic restrictions in the form of reduced diffusion rates of metabolites and ions and their possible selective adsorption on the gel matrix. Diffusion and relaxation characteristics of common solutes in agarose and barium alginate gels were investigated at 37 degrees C by using 1H PFGSE and 23Na TQF NMR spectroscopy. Glucose, glycine, alanine, lactate, sodium ions, and HDO were studied. There were no selective interactions between any of the metabolites and the gel materials but the diffusion coefficients were uniformly reduced. The effects of metabolite diffusion and utilization, in gel beads and threads containing cells, were simulated by using a reaction diffusion model incorporating the measured diffusion coefficients. Metabolism is expected to be very significantly limited by diffusion of solutes to and from the cells that are centrally located within gel threads or spheres of radius approximately 2.0 mm, which is a commonly used size.

Alginates↗
PubMed1995

Ammonia permeability of erythrocyte membrane studied by 14N and 15N saturation transfer NMR spectroscopy.

The permeability of biological membranes to the rapidly penetrating compound ammonia is extremely difficult to study due to the lack of readily available radionuclides. 14N and 15N saturation transfer nuclear magnetic resonance (NMR) experiments were used to measure the erythrocyte membrane permeability of ammonia under equilibrium exchange conditions. When 14N spectra from erythrocytes suspended in NH4Cl solution were obtained in the presence of the extracellular shift reagent dysprosium tripolyphosphate, intracellular and extracellular ammonia signals were readily resolved. Comparison with 15N spectra from erythrocyte suspensions containing 15N4Cl revealed that the intracellular [14N]ammonia signals were 100% NMR visible. 14N and 15N saturation transfer NMR experiments showed similar influx rates and permeabilities, indicating no loss of saturation transfer due to quadrupolar relaxation of 14N nuclei upon membrane passage. Ammonia influx was directly proportional to concentration (0.39 +/- 0.012 fmol.cell-1.s-1.mM-1 at pH 7.0) and not saturable, which is consistent with passive diffusion. Apparent ammonia permeability increased with pH over the range of pH 6-8 as the fraction of free NH3 increased. However, diffusion through unstirred layers became increasingly rate limiting. The permeability of the unstirred layers (1.1 +/- 0.45 x 10(-3) cm/s) was considerably lower than that of NH3 (0.21 +/- 0.014 cm/s). The Arrhenius activation energy for NH3 permeability was 49.5 +/- 11.8 kJ/mol. No evidence for NH+4 influx over the time domain of these experiments was found.

Adult↗
PubMed1995

1H NMR determination of urinary betaine in patients with premature vascular disease and mild homocysteinemia.

Urinary N,N,N-trimethylglycine (betaine) and N,N-dimethylglycine (DMG) have been identified and quantified for clinical purposes by proton nuclear magnetic resonance (1H NMR) measurement in previous studies. We have assessed these procedures by using both one-dimensional (1-D) and 2-D NMR spectroscopy, together with pH titration of urinary extracts to help assign 1H NMR spectral peaks. The betaine calibration curve linearity was excellent (r = 0.997, P = 0.0001) over the concentration range 0.2-1.2 mmol/L, and CVs for replicate betaine analyses ranged from 7% (n = 10) at the lowest concentration to 1% (n = 9) at the highest. The detection limit for betaine was < 15 mumol/L. Urinary DMG concentrations were substantially lower than those of betaine. Urinary betaine and DMG concentrations measured by 1H NMR spectroscopy from 13 patients with premature vascular disease and 17 normal controls provided clinically pertinent data. We conclude that 1H NMR provides unique advantages as a research tool for determination of urinary betaine and DMG concentrations.

Adult↗
PubMed1994

Fructose 3-phosphate and 5-phosphoribosyl-1-pyrophosphate formation in perfused human erythrocytes: 31P NMR studies.

31P NMR was used to study the formation of fructose 3-phosphate (F3P) and 5-phosphoribosyl-1-pyrophosphate (PRPP) in perfused human erythrocytes, in the presence of 10 different combinations and concentrations of glucose, inosine, pyruvate, fructose, and inorganic phosphate (Pi). (1) The cells were immobilized in alginate-coated agarose threads and perfused with a medium containing fructose, and the level of F3P increased continuously over more than 10 h. The net rate of F3P formation was independent of the concentration of 2,3-bisphosphoglycerate (2,3-DPG) present in the cells. (2) PRPP was formed in high concentrations, relative to normal, in immobilized cells when they were perfused with a medium containing Pi at a low pH (6.6). (3) The 2,3-DPG level decreased simultaneously when the sample was perfused with a medium containing fructose, but without inosine or pyruvate. The measured intracellular pH and free Mg2+ concentration were constant in these experiments. (4) The experiments confirmed the presence of fructose-3-phosphokinase (E.C. 2.7.1.-) and ribose-phosphate pyrophosphokinase (E.C. 2.7.6.1) activity in the human erythrocytes and that the biosynthetic pathways are active in immobilized cells at 37 degrees C. (5) The rates of accumulation of 2,3-DPG and phosphomonoesters (PME) appeared to be strongly correlated.

2,3-Diphosphoglycerate↗
PubMed1994

Immobilization methods for NMR studies of cellular metabolism--a practical guide.

Nuclear magnetic resonance (NMR) can be used in a nondestructive manner to study cellular metabolism in intact cell samples such as a suspension of cells. However, many different cell types require a well-regulated medium that includes a buffered pH, as well as a continuous supply of oxygen. A series of methods that have been used for the maintenance of the extracellular conditions involves the immobilization of cells, followed by perfusion of the immobilized cell sample. NMR studies can then be performed for extended periods of time, as well as under sterile conditions. We discuss methodology, with perfused erythrocytes and thymocytes as specific examples.

Alginates↗
PubMed1994

Helodermin, helospectin, and PACAP stimulate cyclic AMP formation in intact bone, isolated osteoblasts, and osteoblastic cell lines.

Helodermin and helospectin are peptides structurally similar to vasoactive intestinal polypeptide (VIP) which were recently isolated from the salivary gland venom of the lizard Heloderma suspectum. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been isolated from ovine hypothalamus and also shows sequence homology to VIP. A helodermin-like peptide has been detected by combined immunohistochemical and immunochemical techniques in the thyroid C-cells. In the present study, lizard helodermin was found to cause a time- and dose-dependent stimulation of cyclic AMP (cAMP) formation in neonatal mouse calvarial bones. Also, helospectin I, PACAP 27, and the C-terminally extended PACAP 38 stimulated cAMP accumulation in the mouse calvariae. The cAMP rise in response to helodermin was comparable to that induced by VIP, both in terms of potency and magnitude of the response. Helodermin, helospectin I, PACAP 27, and PACAP 38, at concentrations of 1 mumol/liter, stimulated cAMP accumulation in enzymatically isolated mouse calvarial bone cells. A significant response to all peptides was observed in both early and late released bone cells isolated from the calvariae, with low and high alkaline phosphatase activity, respectively. Helodermin and VIP stimulated cAMP accumulation in the cloned mouse calvarial osteoblastic cell line MC3T3-E1, in rat (UMR 106-01), and human (Saos-2) osteoblastic osteosarcoma cell lines, but not in the rat osteosarcoma cell line ROS 17/2.8. The effect of helodermin was synergistically and dose-dependently enhanced by forskolin (0.1 and 1 mumol/liter). These data show that bone cells, including osteoblasts, respond to several peptides of the VIP family, including helodermin, helospectin I, PACAP 27, and PACAP 38.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1993

Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology.

Mild homocysteinemia occurs surprisingly often in patients with premature vascular disease. We studied the possible enzymatic sources of this mild hyperhomocysteinemia and the control of homocysteine levels in plasma by treatment of patients with the cofactors and cosubstrates of homocysteine catabolism. We assessed homocysteine metabolism in 131 patients who had premature disease in their coronary, peripheral, or cerebrovascular circulation by using a standard oral methionine-load test. Impaired homocysteine metabolism occurred in 28 patients. We assayed levels of the primary enzymes of homocysteine catabolism in cultured skin fibroblast extracts from 15 of these 28 patients. The patients' cystathionine beta-synthase levels (3.68 +/- 2.52 nmol/h per milligram of cell protein, mean +/- SD) were markedly depressed compared with those from 31 healthy adult control subjects (7.61 +/- 4.49, P < .001). The patients' levels of 5-methyltetrahydrofolate: homocysteine methyltransferase were normal. While betaine: homocysteine methyltransferase was not expressed in skin fibroblasts, 24-hour urinary betaine and N,N-dimethylglycine measurements were consistent with normal or enhanced remethylation of homocysteine by betaine: homocysteine methyltransferase in the 13 patients tested. When treated daily with choline and betaine, pyridoxine, or folic acid, there was a normalization of the postmethionine plasma homocysteine level in 16 of 19 patients. Our results indicate that mild homocysteinemia in premature vascular disease may be caused by either a folate deficiency or deficiencies in cystathionine beta-synthase activity. It does not necessarily involve deficiencies of either 5-methyltetrahydrofolate:homocysteine methyltransferase or betaine:homocysteine methyltransferase. Effective treatment regimens are also defined.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1992

NMR studies of erythrocytes immobilized in agarose and alginate gels.

31P and 13C NMR were used to study the energy metabolism in perfused, human erythrocytes. The erythrocytes were immobilized in agarose threads, Ca- or Ba-alginate beads, and Ba-alginate-coated agarose threads. Erythrocytes were easily washed out from the agarose threads, but not from alginate-containing gels. Various small molecules, such as hypophosphite, dimethyl methylphosphonate, and methylphosphonate, were taken up from the perfusion medium in a normal manner. In addition, the 2,3-bisphosphoglycerate (2,3-DPG) chemical shifts were sensitive to the oxygen partial pressure suggesting that O2 molecules were diffusing through the gel and modifying the binding of 2,3-DPG to hemoglobin. A combination of inosine and pyruvate stimulated the synthesis of 2,3-DPG, but only if inorganic phosphate was present in the perfusion medium. Inosine only resulted in a dramatic rise in the intracellular sugarphosphate concentrations. Furthermore, [2-13C]glucose was converted to [2-13C]lactate by immobilized cells at a rate which was comparable to that in a control suspension. In summary, immobilization in Ba-alginate-coated agarose threads was an efficient way of trapping human erythrocytes for whole cell NMR investigations.

Alginates↗
PubMed1991

The Nordic Expert Group, an inter-Nordic project for assessment of occupational risks.

Risk management and risk control within the occupational environment are individual national issues in the Nordic countries. Within the area of occupational exposure limit setting there is, however, some collaboration. As an internordic project the Nordic Expert Group for Documentation of Occupational Exposure Limits was started in 1977, in order to develop scientific criteria documents. The documents are used by the five national regulatory authorities as a common scientific basis for setting national occupational exposure limits. In risk management in the Nordic countries the Nordic Expert Group deals with the scientific issues and the regulatory authorities deal with the transscientific issues, taking economical aspects and technological feasibility into account. The setting of occupational exposure limits is thus an administrative (or political) concern and the limit values are norms rather than limits between hazardous and nonhazardous concentrations. The work by the Nordic Expert Group exemplifies the fact that the scientific part of risk management can be preferentially performed on an international basis.

Carcinogens↗
PubMed1991

New Swedish occupational standards for some organic solvents.

In 1987, the Swedish government requested a unique investigation of the consequences of a 50% reduction of permissible exposure levels (PEL) for organic solvents. As a result, 29 solvents were investigated and for 25 of them a reduction--if not to 50%--was suggested. For 13 of the solvents, there existed scientific arguments for a reduction of the PEL. For 12 solvents, no specific biomedical information was available. Presumed interactions between solvents may have influenced the decisions, but technological/economic feasibility criteria may also have been used by the regulators. This suggests that the use of technological/economic feasibility criteria can give lower PELs than health criteria. This is within the intentions of the Swedish Work Environment Act.

Acetates↗
PubMed1990

Perturbation of DNA hairpins containing the EcoRI recognition site by hairpin loops of varying size and composition: physical (NMR and UV) and enzymatic (EcoRI) studies.

We have investigated loop-induced structural perturbation of the stem structure in hairpins d(GAATTCXnGAATTC) (X = A, T and n = 3, 4, 5 and 6) that contain an EcoRI restriction site in close proximity to the hairpin loop. Oligonucleotides containing either a T3 or a A3 loop were not hydrolyzed by the restriction enzyme and also showed only weak binding to EcoRI in the absence of the cofactor Mg2+. In contrast, hairpins with larger loops are hydrolyzed by the enzyme at the scission site next to the loop although the substrate with a A4 loop is significantly more resistant than the oligonucleotide containing a T4 loop. The hairpin structures with 3 loop residues were found to be thermally most stable while larger hairpin loops resulted in structures with lower melting temperatures. The T-loop hairpins are thermally more stable than the hairpins containing the same number of A residues in the loop. As judged from proton NMR spectroscopy and the thermodynamic data, the base pair closest to the hairpin loop did form in all cases studied. The hairpin loops did, however, affect the conformation of the stem structure of the hairpins. From 31P and 1H NMR spectroscopy we conclude that the perturbation of the stem structure is stronger for smaller hairpin loops and that the extent of the perturbation is limited to 2-3 base pairs for hairpins with T3 or A4 loops. Our results demonstrate that hairpin loops modulate the conformation of the stem residues close to the loop and that this in turn reduces the substrate activity for DNA sequence specific proteins.

DNA↗