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Biomedical subjects

Claes Andersson

Publications and source records attributed to Claes Andersson.

4 recordsLinked to original sources

Variations in porphobilinogen and 5-aminolevulinic acid concentrations in plasma and urine from asymptomatic carriers of the acute intermittent porphyria gene with increased porphyrin precursor excretion.

BACKGROUND: The heme precursors porphobilinogen (PBG) and 5-aminolevulinic acid (ALA) accumulate during overt crises of acute intermittent porphyria (AIP), and high excretion of these metabolites often continues in the asymptomatic phase. METHODS: We measured concentrations of PBG and ALA and investigated the correlation between these metabolites in plasma and urine in 10 asymptomatic AIP carriers with high excretion and in 5 healthy individuals. We quantified plasma concentrations with an HPLC-mass spectrometric method and urine concentrations with ion-exchange chromatography. RESULTS: The mean (SD) plasma concentrations of PBG and ALA in the AIP carriers were 3.1 (1.0) and 1.7 (0.7) micromol/L, respectively. The mean 8-h urinary excretion amounts of PBG and ALA in the AIP carriers were 102 (25) and 56 (18) micromol, respectively, whereas the corresponding values for healthy individuals were 2.9 (0.7) and 9.3 (1.2) micromol. The correlations between PBG and ALA values in plasma and urine of the AIP carriers were 0.678 and 0.856, respectively. The mean PBG/ALA ratio was approximately 2.0 in both plasma and urine for the AIP carriers and 0.3 in urine for the healthy individuals. The renal clearance rates for PBG and ALA were 71 (15) and 70 (13) mL/min, respectively. CONCLUSIONS: The described HPLC-mass spectrometric method enabled characterization of variations in plasma PBG and ALA in AIP carriers during an 8-h period. The renal clearances were similar for both metabolites. This method could be used to monitor AIP patients during treatment.

Adult↗

Efficacy of enzyme replacement therapy in alpha-mannosidosis mice: a preclinical animal study.

Alpha-mannosidosis is a lysosomal storage disorder which manifests itself in the excessive storage of mannose-containing oligosaccharides in the lysosomes of multiple peripheral tissues and in the brain. Here we report on the correction of storage in a mouse model of alpha-mannosidosis after intravenous administration of lysosomal acid alpha-mannosidase (LAMAN) from bovine kidney, and human and mouse recombinant LAMAN. The bovine and the human enzyme were barely phosphorylated, whereas the bulk of the mouse LAMAN contained mannose 6-phosphate recognition markers. The clearance decreased from bovine to human to mouse LAMAN with plasma half-times of 4, 8 and 12 min, respectively. The apparent half-life of the internalized enzyme was dependent on the enzyme source as well as tissue type and varied between 3 and 16 h. The corrective effect on the storage of neutral oligosaccharides was time-, tissue- and dose-dependent, and the effects were observed to be transient. After a single dose of LAMAN the maximum corrective effect was observed between 2 and 6 days after injection. In general the corrective effect of the human LAMAN was higher than that of the mouse LAMAN and lowest for the bovine LAMAN. Injection of 250 mU human LAMAN/g body weight followed by a subsequent injection 3.5 days later was sufficient to clear liver, kidney and heart from neutral oligosaccharides. Surprisingly a decrease in mannose containing oligosaccharides was also observed in the brain, with storage levels reported at <30% than that found in controls. These data clearly underline the efficacy of enzyme replacement therapy for the correction of storage in alpha-mannosidosis and suggest that this treatment can substantially decrease storage in the brain.

Animals↗

Urban economy as a scale-free network.

We present empirical evidence that land values are scale free and introduce a network model that reproduces the observations. The network approach to urban modeling is based on the assumption that the market dynamics that generates land values can be represented as a growing scale-free network. Our results suggest that the network properties of trade between specialized activities cause land values, and likely also other observables such as population, to be power-law distributed. In addition to being an attractive avenue for further analytical inquiry, the network representation is also applicable to empirical data and is thereby attractive for predictive modeling.

Journal Article↗

Urban growth simulation from "first principles".

General and mathematically transparent models of urban growth have so far suffered from a lack in microscopic realism. Physical models that have been used for this purpose, i.e., diffusion-limited aggregation, dielectric breakdown models, and correlated percolation all have microscopic dynamics for which analogies with urban growth appear stretched. Based on a Markov random field formulation we have developed a model that is capable of reproducing a variety of important characteristic urban morphologies and that has realistic microscopic dynamics. The results presented in this paper are particularly important in relation to "urban sprawl," an important aspect of which is aggressively spreading low-density land uses. This type of growth is increasingly causing environmental, social, and economical problems around the world. The microdynamics of our model, or its "first principles," can be mapped to human decisions and motivations and thus potentially also to policies and regulations. We measure statistical properties of macrostates generated by the urban growth mechanism that we propose, and we compare these to empirical measurements as well as to results from other models. To showcase the open-endedness of the model and to thereby relate our work to applied urban planning we have also included a simulated city consisting of a large number of land use classes in which also topographical data have been used.

Journal Article↗