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Biomedical subjects

E K Johansson

Publications and source records attributed to E K Johansson.

4 recordsLinked to original sources

Adhesion of human myelomonocytic (HL-60) cells induced by 1,25-dihydroxyvitamin D3 and phorbol myristate acetate is dependent on osteopontin synthesis and the alpha v beta 3 integrin.

A key event in bone resorption is the attachment of osteoclasts on the bone surface. Accumulating data supports the notion that this interaction involves the matrix protein osteopontin on the bone surface interacting with a receptor of the integrin family (alpha v beta 3) at the osteoclast clear zone. Based on the recent observation that osteopontin phosphorylation appears to be required for this interaction, it is of considerable interest to delineate the structural requirements for osteopontin-mediated cell attachment. Although binding of isolated osteoclasts to osteopontin-coated surfaces involves the alpha v beta 3 integrin, this system suffers from considerable disadvantages to allow detailed studies in this respect. We have therefore turned to another cell system, HL-60 promyelocytic leukemia cells, to address these questions. In the presence of the phorbol ester TPA (10 nM) and 1,25-dihydroxyvitamin D3 (100 nM), 90% of the HL-60 cells became adherent within 24 hours and exhibited a macrophage-like appearance. Under these conditions, the osteopontin mRNA levels was elevated around 60-fold compared to the control, non-adherent cells. The absolute requirement of de novo osteopontin synthesis for the TPA and 1,25-vit D3-induced HL-60 cell adhesion was demonstrated by neutralisation of adhesion using an anti-osteopontin polyclonal antibody as well as following transfection of an antisense osteopontin phosphorothioate-modified oligonucleotide. Finally, inhibition of induced HL-60 cell adhesion by an RGD-containing peptide or by an antibody to the alpha v beta 3 integrin complex suggested that the cell-derived osteopontin interacts with this integrin. It is concluded that HL-60 cells induced to differentiate with the combination of TPA and 1,25-vit D3 can be utilised as a model system to delineate structural requirements involved in the interaction between osteopontin and the alpha v beta 3 integrin.

Animals

Low levels of essential fatty acids are related to impaired delayed skin hypersensitivity in malnourished chronically ill elderly people.

Essential fatty acid (FA) deficiency, which may accompany protein-energy malnutrition (PEM), has been associated with impaired inflammatory reactions. We evaluated this relationship by analysing FA profiles and delayed cutaneous hypersensitivity in 20 malnourished elderly non-cancer patients and in 20 age-matched control patients. As indicated by serum cholesterol and serum triglycerides, the lipid levels were decreased by about one-third in the subjects with PEM. In comparison with the controls, there was a reduction in the omega 3 FA (e.g. eicosapentanoate) in total serum lipids (mg l-1) and serum phospholipids (%) of 40% and 47%, respectively. Reductions in serum omega 6 FA (e.g. linoleate and arachidonate) levels corresponded to the drop in total FA concentrations (30%). The cutaneous hypersensitivity was impaired in 14 of the malnourished patients. The magnitude of the skin reaction was positively correlated (P < 0.05) to the concentrations of eicosapentanoate in serum lipids and serum phospholipids, as well as to the linoleate concentration in total serum lipids. Six of the malnourished patients took part in a nutritional intervention programme for 3 months. In parallel with an improvement in the nutritional status there was a 35% increase (P < 0.05) in the total omega 3 FA serum concentration. Negative skin tests became positive and the median skin induration enlarged threefold (P < 0.05). Thus, deficiency of omega 3 FA might be one factor contributing to cutaneous anergy in elderly malnourished patients.

Aged

Urinary elimination half-life of delta-1-tetrahydrocannabinol-7-oic acid in heavy marijuana users after smoking.

The urinary excretion of delta 1-tetrahydrocannabinol-7-oic acid (delta 1-THC-7-oic acid), the major urinary metabolite of delta 1-THC, and the total amount of THC metabolites was studied in heavy marijuana users after smoking using high-performance liquid chromatography and the EMT-d.a.u. cannabinoid assay. An average elimination half-life (+/- SD) of 3.0 +/- 2.3 days was obtained for delta 1-THC-7-oic acid. The average ratio (+/- SD) of "EMIT readings"/delta 1-THC-7-oic acid concentrations was 1.23 +/- 1.03.

Adult

Functional and dispositional tolerance develops during continuous cocaine exposure.

Despite the fact that high doses of cocaine are abused chronically, relatively little is known regarding the development of tolerance and/or sensitization under these circumstances. Therefore, male Sprague-Dawley rats were infused continuously i.v. for 10 days, at a rate of 150 mg/kg/day (0.1 mg/kg/min) with cocaine hydrochloride. Body weight, food and water consumption, urine and fecal excretion, as well as blood pressure, heart rate and stereotypic behavior were monitored daily. Blood samples were also drawn daily so that plasma could be analyzed for cocaine and BEG by gas chromatography/mass spectrometry. Severe body weight loss on days 1 through 4 was followed by a gradual return to pre-drug levels. In addition, cocaine's effects on food and water consumption and urine and fecal excretion, which were maximal by day 2, were imperceptible by day 5. Complete tolerance developed rapidly to the remarkable rise in blood pressure noted on the first day. However, tolerance did not develop to the cocaine-induced increase in heart rate. A profound decrease in heart rate was noted in some animals which was interpreted to be cardiotoxicity since these animals subsequently died. On the other hand, sensitization or intensification of behavioral stereotypy occurred during the first 2 days followed by complete tolerance to this effect by day 5. No withdrawal phenomena were noted 24 h after cocaine was abruptly withdrawn. Plasma concentrations of cocaine rose rapidly during the first day and remained elevated at a constant level until day 5. Then, a sharp decline in plasma levels occurred at day 6 which remained depressed for the duration of the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals