Biomedical subjects

E Hansson

Publications and source records attributed to E Hansson.

At least 127 records · Page 7Linked to original sources

PubMed1986

Lipids and fatty acids in membranes from astroglial cells cultured in ethanol-containing media.

A study was undertaken to evaluate the usefulness of a primary brain cell culture for the assessment of general membrane phenomena caused by ethanol. The major aim was to study the inertness versus vulnerability of membrane lipids for 8 days of ethanol exposure. Since brain cells in cultures could be more easily influenced by nutrition than in vivo, effects of varying levels of essential fatty acids in the medium were also studied. Astroglial cells from cerebral hemispheres of newborn rats had a fatty acid composition of major phospholipids resembling that of whole brain. Addition of essential fatty acids to the medium profoundly altered the composition of cell membranes, contrary to what is found in whole animal experiments. Ethanol, in graded levels up to 75 mmol/l and added daily up to 8 days, did not significantly change the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine. The ratio between neutral and acidic phospholipids diminished, which was more pronounced after 8 days of ethanol exposure than after 3 days. This study on ethanol exposure on glial cells focuses on the importance of nutritional composition of culture media and on the role of dynamics among phospholipid classes.

Animals↗

PubMed1986

Increased levels of several retinoid binding proteins resulting from retinoic acid-induced differentiation of F9 cells.

The embryonal carcinoma cell line F9 is known to differentiate when exposed to retinoic acid. We have examined the quantities of two intracellular retinoid-binding proteins in undifferentiated and differentiated F9 cells. The existence of a cell surface receptor that recognizes the plasma retinol-binding protein was also explored. It was shown that undifferentiated F9 cells contain low concentrations of the two retinoid-binding proteins. The cellular retinoic acid-binding protein was present in approximately 3-fold molar excess over the cellular retinol-binding protein. Upon culture in the presence of retinoic acid, F9 cells display elevated concentrations of both cellular retinol-binding protein and cellular retinoic acid-binding protein. Since the levels of beta 2-microglobulin, a marker of the differentiated state with no known involvement in the metabolism of vitamin A, increased in parallel with the retinoid-binding proteins, it seems unlikely that retinoic acid selectively increased the levels of the two retinoid-binding proteins. The differentiated, in contrast to the undifferentiated cells, can accumulate retinol from plasma retinol-binding protein and display a cell surface receptor for this protein. Despite the fact that retinoic acid-induced differentiation of F9 cells promotes increased levels of several proteins involved in the normal metabolism of vitamin A, no evidence was obtained to suggest that the cells were dependent on retinoids to maintain their differentiated state.

Animals↗

PubMed1985

Cellular retinoid binding proteins.

The cellular retinol-binding protein (CRBP) and the cellular retinoic acid binding protein (CRABP) have similar physicochemical characteristics. The amino acid sequences of rat CRBP and bovine CRABP have been elucidated and they display 40% sequence identity. Both protein sequences appear to be evolutionarily highly conserved. The amino acid sequence of human CRBP, deduced from a cDNA-clone, is 96% identical to the rat CRBP sequence. CRBP and CRABP are members of a protein family, all members of which may bind hydrophobic ligands and interact with membrane components. All members of the protein family are probably related in tertiary structure and might interact with membrane components through two regions with a high probability for alpha-helix. The tissue distribution of CRBP and CRABP, together with their relation to lipid transporting proteins suggests that CRBP and CRABP are cellular transporting proteins for retinol and retinoic acid, respectively.

Amino Acid Sequence↗

PubMed1985

Amino acid incorporation during morphine intoxication. I: Dose and time effects of morphine on protein synthesis in specific regions of the rat brain and in astroglia-enriched primary cultures.

Uptake and incorporation of 3H-valine into soluble protein were studied in normal and in physically dependent rat brain, or in astroglial primary cultures at various times after the administration of morphine at different doses. There was an increased protein synthesis in striatum and brain stem of previously untreated rats 2-3 hr after low-dose morphine administration (10 mg/kg bw IP). The changes were completely reversed by naloxone (5 mg/kg bw, IP) administered 10 min prior to the morphine. During the first hour after IP administration of 25 mg morphine/kg bw there was a decrease in striatum and brain stem protein synthesis, followed by an increase in brain stem protein synthesis between 2 and 3 hr later. These changes were blocked by naloxone. In all brain regions studied 40 mg morphine/1 kg bw, IP inhibited protein synthesis, an effect partially reversed by naloxone (5 mg/kg bw, IP). Similar dose- and time-dependent effects were obtained from primary astroglia-enriched cultures from cerebral hemispheres, suggesting that low or moderate doses of morphine affect brain cell protein synthesis. At least one phase of increased synthesis was seen, but within a few hours of a high morphine dose the protein synthesis was decreased. After long-term morphine intoxication (13 days; final dose 340 mg/kg bw/day po) incorporation of 3H-valine in vivo into TCA-precipitable soluble proteins during 60 min decreased in the hypothalamus and in the occipital and entorhinal cortex, and was unchanged in other brain regions examined. An IP injection of morphine (10 or 25 mg/kg bw/day) to such animals resulted in a pronounced and rapidly occurring increase in protein synthesis in many brain regions. This was further demonstrated with gel electrophoresis in brain stem and hypothalamus, where higher 3H-labeling was seen in many protein bands. The labeling of one band from brain stem having approx 80,000 MW was especially pronounced. Incorporation of 3H-valine into membrane-bound proteins of brain stem changed in a similar way to the soluble proteins, but was not as pronounced.

Amino Acids↗

PubMed1985

Amino acid incorporation during morphine intoxication. II: Electrophoretic separation of extracellular proteins from cerebral hemisphere slices and astroglia-enriched primary cultures.

Radioactively labeled proteins were identified in a broad molecular weight range in the incubation medium of rat cerebral hemisphere slice preparations or primary cultures after incubation with radioactive valine. Morphine chloride caused an increase in labeled media proteins with MW approximately 40,000 and 65,000 in both preparations, whereas a fraction with MW, approximately 80,000 decreased in amount. In the culture preparation a MW approximately 15,000 fraction also decreased after morphine treatment. The effects on the MW 40,000 and 65,000 fractions by morphine could not be blocked by naloxone hydrochloride, an opiate antagonist. Labeled media proteins from primary cultures obtained from various brain regions showed many similarities. After 10(-5) or 10(-6) M morphine, protein fractions with MW approximately 15,000, 25,000, 40,000, 65,000-70,000, 80,000, and 100,000 changed with increases or decreases in the various morphine concentrations. The 3H-labeling of the MW approximately 40,000 fraction increased in all cultures, where it decreased. In conclusion, proteins synthesized within cells in brain slices or in astroglia-enriched cultures are released or secreted into the incubation media. Some protein fractions are affected in different directions by morphine. The effects were not correlated with the presence of classical opiate receptors on the cells. This was so even though more changes in media proteins occurred in astroglial cultures from opiate receptor-rich brain regions than in similar cultures from opiate receptor-poor regions. The possible significance of proteins synthesized in astroglial cells and released extracellularly in opiate action is discussed.

Amino Acids↗

PubMed1985

Transport of monoamine and amino acid neurotransmitters by primary astroglial cultures.

The transport of [3H]L-glutamate, [3H]L-aspartate, [3H] gamma-aminobutyric acid [( 3H]GABA), [3H]dopamine, [3H]norepinephrine and [3H]5-hydroxytryptamine (3H-5-HT) was measured in primary astroglial cultures from newborn rat cerebral hemispheres. There was a high-affinity uptake with a Km of 69.0 microM for L-glutamate, 12.3 microM for L-aspartate and 3.1 microM for GABA. The uptake showed properties of high capacity with a Vmax of 17.0 nmol X mg prot-1 X min-1 for L-glutamate, 1.1 nmol X mg prot-1 X min-1 for L-aspartate and 0.04 nmol X mg prot-1 X min-1 for GABA. No high-affinity high capacity transport system was found for the monoamines studied. Autoradiographic examination demonstrated a heavy deposit of grains suggesting a prominent accumulation of [3H]L-glutamate and [3H]L-aspartate in the astroglial-like cells of the cultures, while the [3H]GABA accumulation was less intense. On the other hand, there was only a weak accumulation of grains after incubating the cultures with [3H]dopamine, [3H]norepinephrine or [3H]5-HT. Thus, astroglial cells in culture accumulate amino acid neurotransmitters and monoamines in different ways with a high-affinity high-capacity uptake of glutamate, aspartate and GABA and a diffusion-uptake of dopamine, norepinephrine and 5-HT.

Amino Acids↗

PubMed1985

Amino acid and monoamine transport in primary astroglial cultures from defined brain regions.

The uptake of L-[3H]glutamate, L-[3H]aspartate, gamma-[3H]aminobutyric acid (GABA), [3H]dopamine, DL-[3H]norepinephrine and [3H]5-hydroxytryptamine (5-HT) was studied in astrocytes cultured from the cerebral cortex, striatum and brain stem of newborn rat and grown for 2 weeks in primary cultures. The astrocytes exhibited a high-affinity L-glutamate uptake with Km values ranging from 11 to 110 microM. Vmax values were 4.5 in cerebral cortex, 39.1 in striatum, and 0.4 in brain stem, nmol per mg cell protein per min. There was a less prominent high-affinity uptake of L-aspartate with Km values from 88 to 187 microM. Vmax values were 7.4 in cerebral cortex, 37.1 in striatum, and 3.1 in brain stem, nmol per mg cell protein per min. The high-affinity GABA uptake exhibited Km values ranging from 5 to 17 microM and Vmax values were 0.01 for cerebral cortex, 0.04 for striatum, and 0.1 for brain stem, nmol per mg cell protein per min. No high-affinity, high-capacity uptake was found for the monoamines. The results demonstrate a heterogeneity among the astroglial cells cultivated from the different brain regions concerning the uptake capacity of amino acid neurotransmitters. Furthermore, amino acid transmitters and monoamines are taken up by the cells in different ways.

Amino Acids↗

PubMed1985

Primary cultures from defined brain areas; effects of seeding time on cell growth, astroglial content and protein synthesis.

The influence of seeding time on cell growth, astroglial content and on protein synthesis during cultivation was determined in primary cultures from 3 phylogenetically different brain areas from rat cerebral cortex, striatum and brainstem. Brainstem cultivated from 17-day-old embryos and all the cultures studied from the 3 brain areas of newborn and 7-day-old rat showed a similar increase in total and water-soluble protein during cultivation. Glial fibrillary acidic protein (GFAp, alpha-albumin) levels increased with age in all cultures studied. There was a rapid increase in GFAp (alpha-albumin) between 1 and 2 weeks in cultures from newborn and between 2 and 3 weeks in brainstem cultures from 17-day-old embryos, these increases being slower thereafter. Incorporation of [3H]valine into soluble protein was lower in 3-week-old cultures than in 1- and 2-week-old cultures derived from newborn and 7-day-old rat brain. The incorporation rates were similar in comparisons of the various cultures. Similar results were obtained from embryonic cultures, although the decrease in incorporation rate was between 3 and 4 weeks. The efficiency of incorporation (% TCA-precipitated material/total [3H]activity) was higher in 2- and 3-week-old than in 1-week-old cultures from newborn and 7-day-old rats and in 3- and 4-week-old cultures of brainstem from 17-day-old rat embryos. These findings suggest a cell differentiation during cultivation. The results show that seeding time has a variable influence on cultures from the different brain areas studied concerning cell growth, astroglial content and probably differentiation during cultivation. Embryonic cell cultures seem, in general, to develop one week later than neonatal and postnatal ones. Cultures of newborn rat cells from cerebral cortex, striatum and brainstem show many similarities in the above parameters during cultivation. This is also the case for brainstem cultures from embryonic rat.

Albumins↗

PubMed1985

Primary cultures from defined brain areas; effects of seeding time on the development of beta-adrenergic- and dopamine-stimulated cAMP-activity during cultivation.

The influence of seeding time on the expression of beta-adrenergic- and dopamine-stimulated cAMP activity was studied in primary astroglial cultures from various brain areas. In all cultures isoproterenol (10(-7)-10(-5) M) caused an increased cAMP accumulation with time in culture. In brainstem cultures from 17-day-old embryos there was a decreased intracellular cAMP accumulation between 3 and 4 weeks. In all newborn rats and in striatal cultures from 7-day-postnatal rats there was a similar decrease between 2 and 3 weeks. These changes are discussed and interpreted as a differentiation of the cells concerning beta-receptors. The most prominent cAMP accumulation caused by isoproterenol was found in striatal cultures from newborn rat. Although isoproterenol and noradrenaline both caused intracellular cAMP accumulation, isoproterenol was the most effective. There was a cAMP accumulation specific to dopamine (10(-6)-10(-4)M) in 2-week-old striatal cultures from newborn rat, although there was an interaction with beta-adrenergic receptors. In the other cultures studied there was only a very small dopamine stimulation of cAMP. The expression of this heterogeneity among astroglial primary cultures from various brain areas seems to be influenced by the genetic program for cellular maturation and by specific cellular contacts in vivo until seeding and in culture.

Animals↗

PubMed1985

Toxicological studies on omeprazole.

As part of the safety evaluation of the gastric antisecretory drug, omeprazole, toxicological studies have been performed in several species of animals. The acute toxicity after oral administration to rodents was low. The oral LD50 value was above 4 g/kg. The general toxicity after repeated administration has been studied in rats and dogs. No clinical signs of adverse reactions were seen. Some minor changes in hematology parameters were observed. In rats and mice decreases in the erythrocyte count, hematocrit and hemoglobin have occasionally been found at doses of 125 mumol/kg/day and more. Hyperplasia of oxyntic mucosal cells, concomitant with increases in stomach weight, oxyntic mucosal thickness and folding, has been observed in the species investigated, the dog, rat and mouse. In addition, slight chief cell atrophy and eosinophilia of the chief cell granules were observed in rats. The oxyntic mucosal effects were reversible upon treatment being discontinued. In the oncogenicity studies, gastric carcinoids occurred in the rat but not in the mouse. Investigations of the carcinoids showed that the vast majority of the endocrine cells could be characterised as ECL-cells. The hyperplasia of oxyntic mucosal cells, including hyperplasia of endocrine ECL-cells and development of gastric carcinoids in rats, is attributable to the pronounced hypergastrinemia produced as a secondary effect of almost complete inhibition of acid secretion by the large doses of omeprazole used in the toxicity studies. In agreement with this hypothesis, the hyperplasia of the oxyntic cells was prevented by antrectomy. The reproduction studies performed in rats and rabbits showed no sign of fetal toxicity or teratogenic effect. The results of the short-term mutagenicity tests, Ames test, the micronucleus test in mice and the mouse lymphoma test were all negative.

Administration, Oral↗

PubMed1985

Early results of the Finnish Multicentre Study of Prostatic Cancer (Finnprostate).

Four hundred and four prostatic cancer patients diagnosed in the years 1979-1982 in nine Finnish hospitals have been followed up for a mean period of three years. The aim of this study is to evaluate the situation of this malignancy in the Finnish male population and to discuss the diagnostic procedures and treatment modalities. In one fifth of the patients the carcinoma was as incidental finding on microscopical examination of tissue removed by transurethral resection or enucleation for presumed benign prostatic hyperplasia. At the diagnostic moment 69% of the tumours were locally advanced beyond the prostatic capsule and one third of all cases had metastasized. 134 out of 404 (33%) have died and 45% of these of prostatic cancer. Survival was adversely affected by the tumour differentiation grade. In non-metastasized cases the local extent of the tumour had no notable effect on prognosis. Some early comparisons are made between orchidectomy and oestrogen therapy.

Acid Phosphatase↗

PubMed1984

Cellular composition of primary cultures from cerebral cortex, striatum, hippocampus, brainstem and cerebellum.

Primary cultures from newborn rat cerebral cortex, striatum, hippocampus, brainstem and cerebellum were grown for 14 days. There was a linear relationship between the amount of material seeded and the protein content of the respective culture. The amount of tissue material seeded was selected so that the different cultures reached confluence at 6-7 days and contained similar amounts of protein when 7 and 14 days old. The cellular content was evaluated by astroglial markers, such as the glial fibrillary acidic protein (GFAp; alpha-albumin) and the S-100 protein, and by markers for other cells expected to be in the cultures (14-3-2 protein, macrophage acidic protein (MAP), alkaline phosphatase, myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP]. Astroglial-like cells represented 60-70% of the cells present in the different cultures. Quantitation of GFAp (alpha-albumin) showed similar amounts to be present in cultures from cerebral cortex, hippocampus and striatum; however, on lower levels expressed in soluble proteins than in the corresponding brain regions of adult rats. Brainstem of adult rat contained large amounts of GFAp (alpha-albumin), while low levels were found in brainstem culture. Also, phagocytic cells (macrophages), endothelial-like cells, mesenchymal-like cells, ependymal-like cells and oligoblasts were found. Neither mature neurons, nor oligodendroglial cells were observed. It is concluded that although there might be some differences in the degree of maturation or in the cellular composition of the various cultures, they could serve as a good model system for studying the characteristics of astroglial cells from various brain regions.

Animals↗

PubMed1984

Cellular composition of a cerebral hemisphere primary culture.

In this overview attention is given to available markers and methods for characterizing cell elements in a culture system. Primary cultures from newborn rat cerebral hemispheres were grown for 14 days. The population of cells was dominated by astrocytic glial cells (60-70%), but cells with properties of macrophages, endothelial-like cells, mesenchymal-like cells, ependymal-like cells, and oligoblasts were also found. Neither mature neurons nor oligodendroglial cells were observed. The enrichment in astroglial-like cells makes the cultures a satisfactory astroglial-cell model, at least for some purposes.

Aging↗

PubMed1984

Is there a "dopaminergic glial cell"?

Intracellular cAMP increased 9-fold in cerebral hemisphere primary cultures after incubation with dopamine (10(-4) M). The effect was dose- and time-dependent (10(-6) M-10(-4) M; 2-10 minutes). It was mimicked, to some extent, by the partial agonist apomorphine (10(-5) M-10(-4) M) and antagonized by fluphenazine (10(-5) M-10(-4) M). The elevation of cAMP caused by dopamine was incompletely antagonized by propanolol (10(-5) M-10(-4) M), obviating an interaction with beta-adrenergic receptors. A beta-adrenergic effect was antagonized by propranolol but only slightly by fluphenazine. The effect of dopamine on cAMP-level was more pronounced in a subpopulation of the hemisphere culture, i.e. in astroglial cultures from the striatum, 12-fold compared with controls at 10(-4) M. No dopamine stimulated formation of cAMP was found in primary cultures from brain-stem. The results demonstrated some heterogeneity among astroglial cells. The cultures used contained mainly astroglial-like cells, as judged from immunohistochemical localization of the glial specific proteins S 100 and GFA (alpha-albumin). No mature neurons or oligodendroglial cells have so far been demonstrated in the cultures.

Animals↗

PubMed1984

Enzyme activities of monoamine oxidase, catechol-O-methyltransferase and gamma-aminobutyric acid transaminase in primary astroglial cultures and adult rat brain from different brain regions.

The activities of monoamine oxidase (MAO), catechol-O-methyltransferase (COMT) and gamma-aminobutyric acid transaminase (GABA-T) were measured in primary cultures from newborn rat cultivated from 6 different brain regions. These primary cultures contained mostly astroglial cells, evaluated by the presence of the glial fibrillary acidic protein (GFAp, alpha-albumin) and the S-100 protein. The enzyme activities in the corresponding brain area from adult rat were also quantified. MAO activities were on the same level in 14-day old cultures and in adult rat brain homogenates, with significantly lower values in brain stem as compared to the other brain regions examined. COMT activities were on a higher level in the cultures than in adult rat brain homogenates. Astroglial cells from hippocampus were found to have the highest and those from brain stem the lowest COMT-activities. GABA-T activities were lower in the cultures than in adult rat homogenates. No significant differences were seen in the various astroglial cultures. Accumulation of [3H]dopamine and [3H]gamma-aminobutyric acid (GABA) visualized by autoradiography showed only a slight uptake of dopamine in comparison with the uptake of GABA. It is concluded that astroglial cells in culture have enzymatic properties similar to those of astroglial cells in different brain regions of adult rat brain. Studies are in progress to evaluate if the regional heterogeneity observed among cultivated astroglial cells is affected by in vivo differentiation until cultivation and/or time in culture.

4-Aminobutyrate Transaminase↗

PubMed1984

Genetic and phenotypic characteristics of a new group of Campylobacter isolated from pigs and cattle.

Five intestinal strains of Campylobacter isolated from pigs and cattle are described. The strains grew in anaerobic as well as in micro-aerobic environment; they were catalase positive and resistant to nalidixic acid but sensitive to cephalothin and metronidazole. They had a mean G+C content of 35.4 mol %. DNA-DNA-hybridizations showed that the group was homogeneous: about 50% related to C. fetus ss fetus and less than 25% related to other Campylobacter species.

Animals↗

PubMed1984

Characteristics of dopamine and GABA transport in primary cultures of astroglial cells.

Primary astroglial cultures were grown from newborn rat cerebral hemispheres. Cultures, aged 7 and 14 days, were analysed with respect to their capacity to accumulate radioactive GABA and dopamine. Concentrative high-affinity uptake, showing Na+-dependence was observed for GABA where Km and Vmax were not significantly altered with age of the culture. No Na+-dependent high-affinity transport of dopamine was observed. The addition of 0.1 mM dibutyryl-cyclic-3'-5'-adenosinemonophosphate (dB-cAMP) after removal of fetal calf-serum reduced the Vmax as well as the Km of 3H-GABA uptake. The ionic dependence of 3H-GABA and 3H-dopamine was not significantly altered following this treatment. The results are difficult to interpret in terms of a potentiated differentiation of the cells.

Age Factors↗

PubMed1983

Accumulation of putative amino acid neurotransmitters, monoamines and D-Ala2-Met-enkephalinamide in primary astroglial cultures from various brain areas, visualized by autoradiography.

The accumulation of amino acids, monoamines and D-Ala2-Met-enkephalinamide (Enk) was visualized by autoradiography in astroglial primary cultures from different well-defined brain areas. The most prominent accumulation of grains was seen after incubating astroglial cultures from cerebral cortex, hippocampus and striatum with glutamate. Less uptake was seen in brainstem and cerebellar cultures. Similar results were found with aspartate but at a lower uptake level. The accumulation of GABA was moderate in all cultures studied. Dopamine, norepinephrine and 5-hydroxytryptamine (5-HT) showed only a slight accumulation and enkephaline did not accumulate at all. The results demonstrate that astroglial cells are not general inactivators for neurotransmitters, as monoamines are taken up only slightly and enkephalin not at all, while the cells have the capacity to accumulate at least some amino acid neurotransmitters. Furthermore, astroglial cells from different brain regions have different capacities to accumulate the various amino acid neurotransmitters supporting the view of regionally specialized astroglial cells.

Amino Acids↗