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Biomedical subjects

T Björkman

Publications and source records attributed to T Björkman.

4 recordsLinked to original sources

Accessible hyaluronan receptors identical to ICAM-1 in mouse mast-cell tumours.

Immunohistochemical studies of the hyaluronan (HA)-receptor (R), originally found on liver endothelial cells (LEC) and related to the intercellular adhesion molecule 1 (ICAM-1), showed that polyclonal antibodies against HARLEC (HA receptor on LEC) also stain structures in mouse mastocytomas, mainly vessels. To test if intravenously administered HA might target the tumour receptors in vivo, mice carrying an inoculated mastocytoma in one hind leg muscle were injected in the tail vein with 125I-tyrosine (T)-labelled HA and killed 75 min after injection when organs and tissues were checked for radioactivity. When doses exceeding the binding capacity of the liver were injected, a significant increase in radioactivity (up to five-fold) within the tumour tissue was found. The weight adjusted difference between control and tumour tissue was greater for smaller tumours, probably due to necrosis in the larger. HA-staining of tumours from animals receiving 125I-T-HA, showed HA in areas that also stained weakly for ICAM-1 using monoclonal antibodies. ICAM-1 staining was dramatically increased after hyaluronidase treatment of the sections, indicating that the HA is bound to these receptors and thereby blocks antibody recognition.

Animals

Labelling of high molecular weight hyaluronan with 125I-tyrosine: studies in vitro and in vivo in the rat.

Studies on the metabolism of the polysaccharide hyaluronan has previously been hampered by the lack of radioactive hyaluronan of high molecular weight (MW) and high specific activity. In the present study 125I-tyrosine (T)-labelled hyaluronan was produced after CNBr-activation of the polysaccharide. A specific activity of approximately 0.1 MBq microgram-1 was achieved using 100 micrograms of 0.5 x 10(6) Da hyaluronan labelled for 2 h with 18 MBq 125I. The 125I-T-hyaluronan kept a high MW-profile upon gel filtration chromatography and was found to be cleared from the circulation with the kinetics and organ distribution reported for biosynthetically labelled hyaluronan of high MW. The 125I-labelled polysaccharide is also taken up by liver endothelial cells both in vivo and in vitro, indicating that the labelling does not interfere with the binding to specific cell-surface receptors found on these cells. The intracellular degradation is slower than that earlier reported for biosynthetically labelled hyaluronan and seems to be halted at the level of low MW oligo- or mono-saccharides that eventually leave the organism via the urine. Scintigraphic images of rats after intravenous injection of 125I-T-hyaluronan showed rapid uptake in the liver and a redistribution of radioactivity from liver to urine with time. Our results indicate that the 125I-T-hyaluronan is suitable for studies of hyaluronan-metabolism in a number of ways. The gamma emitters 125I and 131I are easy to monitor and can be used also for in vivo 3D-imaging using single photon emission computer tomography.

Animals

Mechanisms of stimulation of acid production in parietal cells isolated from the pig gastric mucosa.

Sequential incubations with pronase and collagenase of pig gastric mucosa resulted in single cell preparations containing 10-20% parietal cells, which could be enriched further to 85-95% purity by density-gradient centrifugation followed by elutriation. Acid production of the isolated cells was measured by means of aminopyrine accumulation in their acid compartments. When small pieces of the mucosa were pretreated for 1 h in the presence of either histamine, pentagastrin or carbachol before preparation of cells, the ability of the subsequently isolated cells to produce acid was increased. In parietal cells isolated from resting (not pretreated) mucosa pentagastrin, carbachol and also adrenaline increased the histamine-stimulated aminopyrine accumulation (50-90% increase). Adrenaline alone had no significant effect on the aminopyrine accumulation. In the presence of 10(-4) M histamine the apparent EC50 for adrenaline was 5 X 10(-7) M. Adrenaline, histamine, forskolin and isobutylmethylxanthin (IBMX) increased the formation of cAMP in purified parietal cells. The three 'classical' secretagogues histamine, pentagastrin and carbachol, but also IBMX and forskolin, increased the cytosolic free Ca2+ from approximately 1.5 X 10(-7) M to 2.2-3.5 X 10(-7) M but adrenaline and dibutyryl cyclic AMP did not. Thus the present results indicate that there are - in addition to histaminergic H2 receptors - specific cholinergic, gastrinergic and adrenergic receptors on the plasma membrane and that there are separate cAMP and Ca2+-dependent stimulatory pathways in the parietal cell.

8,11,14-Eicosatrienoic Acid