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K R Norum

Publications and source records attributed to K R Norum.

At least 55 records · Page 3Linked to original sources
PubMed1992

Reduced concentration of hepatic alpha-tocopherol in patients with alcoholic liver cirrhosis.

The concentration of alpha-tocopherol was measured in liver biopsy specimens obtained from 83 patients with alcoholic and non-alcoholic liver diseases. The mean hepatic vitamin E content (as alpha-tocopherol) was significantly lower in 23 patients with alcoholic cirrhosis (17.6 +/- 12.1 nmol/mg wet weight liver), compared with 12 patients with normal liver histology (39.2 +/- 29.7 nmol/mg, P less than 0.01). The mean serum concentration of alpha-tocopherol was lower in patients with alcoholic cirrhosis (13.9 +/- 7.0 mumol/l) than in individuals with alcoholic fatty liver (21.3 +/- 9.3 mumol/l, P less than 0.01) and patients with normal liver histology (23.4 +/- 11.6 mumol/l, P less than 0.01). A decreased ratio of serum alpha-tocopherol/total serum lipids was also observed in patients with alcoholic cirrhosis, compared with patients with normal liver histology (P less than 0.05). There was a significant correlation between concentrations of alpha-tocopherol in liver and serum (r = 0.43, P less than 0.001). Furthermore, serum alpha-tocopherol correlated with retinol (r = 0.53, P less than 0.001), selenium (r = 0.45, P less than 0.001), and albumin (r = 0.37, P less than 0.001) in serum. We suggest that the reduced content of hepatic alpha-tocopherol observed in some patients may play a role in ethanol-induced lipid peroxidation.

Adolescent↗
PubMed1991

[Food and health].

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Feeding Behavior↗
PubMed1991

Retinyl esters in chylomicron remnants inhibit growth of myeloid and lymphoid leukaemic cells.

We have studied the effects of retinyl esters in chylomicron remnants on cell growth and differentiation of myeloid and lymphoid leukaemic cells. Ten mumol l-1 retinyl ester in chylomicron remnants effectively reduced proliferation of the myeloid leukaemic cell lines HL60, U937 and KG-1, and induced differentiation of 68% and 53% of the HL60 and U937 cells, respectively, in 5 days. While no effect on cell growth of the lymphoid cell lines Daudi, Raji and SOS was observed, 10 mumol 1-1 retinyl esters in chylomicron remnants reduced the growth of the B lymphoid cell line Reh by more than 50%. Primary cell cultures from six patients with acute leukaemia (four non-lymphocytic and two lymphocytic) were incubated with chylomicron remnant retinyl esters and proliferation was measured by means of thymidine incorporation. Among the myeloid leukaemic cells, the monomyelocytic, the two promyelocytic and the monoblastic leukaemic cells were growth inhibited. Chylomicron remnants had no effect on the growth of the c-ALL primary culture, but reduced proliferation of the T-ALL primary culture by approximately 20% after 48 h. These data suggest that high doses of retinol may be used in the treatment of some forms of acute leukaemia.

Cell Differentiation↗
PubMed1991

Cultivation of HL-60 cells in a serum-free medium containing granulocyte/macrophage colony-stimulating factor.

In order to develop a defined cultivation medium for HL-60 cells, we cultivated these cells in a serum-free suspension medium and tested the effect of various growth factors. Of the factors tested, granulocyte/macrophage colony-stimulating factor was most active in growth stimulation. A much lower effect was obtained with granulocyte colony-stimulating factor and transferrin. No effect was found with interleukin-3 and insulin. Granulocyte colony-stimulating factor was the only growth factor tested that also induced differentiation as judged by the nitroblue tetrazolium test. Growth of HL-60 cells in medium containing granulocyte/macrophage colony-stimulating factor (125 U/ml) and transferrin (5 micrograms/ml) as the only protein factors was similar to growth in medium containing 10% serum. No increase in spontaneous differentiation of HL-60 cells in this defined medium was observed. Physiological concentrations of retinol bound to retinol-binding protein and retinyl ester in chylomicron remnants reduced proliferation as well as the level of c-myc oncoprotein and induced differentiation of HL-60 cells cultivated in defined medium. Hence, this defined medium may be useful when studying the function of retinoids in HL-60 cells.

Animals↗
PubMed1990

Transport and storage of vitamin A.

The requirement of vitamin A (retinoids) for vision has been recognized for decades. In addition, vitamin A is involved in fetal development and in the regulation of proliferation and differentiation of cells throughout life. This fat-soluble organic compound cannot be synthesized endogenously by humans and thus is an essential nutrient; a well-regulated transport and storage system provides tissues with the correct amounts of retinoids in spite of normal fluctuations in daily vitamin A intake. An overview is presented here of current knowledge and hypotheses about the absorption, transport, storage, and metabolism of vitamin A. Some information is also presented about a group of ligand-dependent transcription factors, the retinoic acid receptors, that apparently mediate many of the extravisual effects of retinoids.

Animals↗
PubMed1990

Effect of retinoids and 1,25(OH)2 vitamin D3 bound to their plasma transport proteins on growth and differentiation of HL-60 cells.

We have compared the effect of physiological and pharmacological concentrations of retinoids and 1,25(OH)2 vitamin D3 bound to their plasma transport proteins upon the proliferation and differentiation of HL-60 cells. Concentrations of chylomicron remnant retinyl ester similar to that obtained in plasma after a vitamin A-rich meal reduced the proliferation in more than 50% of HL-60 cells. Pharmacological concentrations of chylomicron remnant retinyl ester completely blocked the proliferation of the cells, and induced differentiation in 60% of the cells after 5 days. Physiological and pharmacological concentrations of retinoic acid bound to albumin had comparable effects. In contrast to earlier published data, which have been obtained with retinoids dissolved in ethanol, our results suggest that physiological and pharmacological concentrations of retinol (i.e. retinyl esters in chylomicron remnants) are as active as retinoic acid in reduction of proliferation and induction of differentiation of HL-60 cells. Physiological concentrations of 1,25(OH)2 vitamin D3 bound to vitamin D-binding protein (DBP) and retinol bound to retinol-binding protein had only a small effect on differentiation and proliferation of HL-60 cells.

Calcitriol↗
PubMed1990

Internalization of retinol-binding protein in parenchymal and stellate cells of rat liver.

We have studied uptake of retinol-binding protein (RBP) by rat liver cells. First, we compared the in vivo uptake in different liver cells of 125I-labeled RBP with that of other well-known ligands. We found that the ligands studied were recognized differently by the various cell types in the liver, and that RBP was most efficiently taken up by parenchymal and stellate cells. We then studied the in vivo uptake of RBP in liver cells by immunocytochemistry at the electron microscopic level using ultrathin cryosections. Ten min after injection, RBP was localized to parenchymal cells and stellate cells. In these cells, RBP was detected on the cell surface and in vesicles near the cell surface. RBP was observed mainly in association with the membrane in these vesicles. Two hours after injection, RBP was localized not only on the cell surface and in vesicles close to the cell surface, but also in larger vesicles located deeper in the cytoplasm of these cells. RBP in larger vesicles was observed at a distance from the vesicular membrane. Finally, we compared the distribution of endocytosed RBP in liver parenchymal cells with that of asialo-orosomucoid, a ligand known to be internalized by receptor-mediated endocytosis. We detected both ligands on the cell surface and in small vesicles located close to the cell surface and in larger vesicles located deeper in the cytoplasm. Asialo-orosomucoid and RBP were seldom observed in the same small vesicles, but the larger vesicles contained both ligands. These data suggest that RBP is internalized in parenchymal and stellate cells of the liver by receptor-mediated endocytosis.

Animals↗
PubMed1989

Low-density-lipoprotein receptors in different rabbit liver cells.

Receptor-dependent uptake mechanisms for low-density lipoprotein (LDL) were studied in rabbit liver parenchymal and non-parenchymal cells. Hybridization studies with a cDNA probe revealed that mRNA for the apo (apolipoprotein) B,E receptor was present in endothelial and Kupffer cells as well as in parenchymal cells. By ligand-blotting experiments we showed that apo B,E-receptor protein was present in both parenchymal and non-parenchymal cells. Studies of binding of homologous LDL in cultured rabbit parenchymal cells suggested that about 63% of the specific LDL binding was mediated via the apo B,E receptor. Approx. 47% of the specific LDL binding was dependent on Ca2+, suggesting that specific Ca2+-dependent as well as Ca2+-independent LDL-binding sites exist in liver parenchymal cells. Methylated LDL bound to the parenchymal cells in a saturable manner. Taken together, our results showed that apo B,E receptors are present in rabbit liver endothelial and Kupffer cells as well as in the parenchymal cells, and that an additional saturable binding activity for LDL may exist on rabbit liver parenchymal cells. This binding activity was not inhibited by EGTA or reductive methylation of lysine residues in apo B. LDL degradation in parenchymal cells was mainly mediated via the apo B,E receptor.

Animals↗
PubMed1989

Intracellular transport of formaldehyde-treated serum albumin in liver endothelial cells after uptake via scavenger receptors.

Endocytosis of formaldehyde-treated serum albumin (FSA) mediated by the scavenger receptor was studied in rat liver endothelial cells. Suspended cells had about 8000 receptors/cell, whereas cultured cells had about 19,000 receptors/cell. Kd was 10(-8) M in both systems. Cell-surface scavenger receptors were found exclusively in coated pits by electron microscopy, by using ligand labelled with colloidal gold. Cell-surface-bound FSA could be released by decreasing the pH to 6.0; it was therefore possible to assess the rate of internalization of surface-bound ligand. This rate was very high: t1/2 for internalization of ligand prebound at 4 degrees C was 24 s. The endocytic rate constant at 37 degrees C, Ke, measured as described by Wiley & Cunningham [(1982) J. Biol. Chem. 257, 4222-4229], was 2.44 min-1, corresponding to t1/2 = 12 s. Uptake of FSA at 37 degrees C after destruction of one cell-surface pool of receptors by Pronase was decreased to 60%. This finding is compatible with a relatively large intracellular pool of receptors. The intracellular handling of 125I-tyramine-cellobiose-labelled FSA (125I-TC-FSA) was studied by subcellular fractionation in sucrose gradients, Nycodenz gradients or by differential centrifugation. The density distributions of degraded and undegraded 125I-TC-FSA after fractionation of isolated non-parenchymal cells and whole liver were similar, when studied in Nycodenz and sucrose gradients, suggesting that the subcellular distribution of the ligand was not influenced by the huge excess of non-endothelial material in a whole liver homogenate. Fractionation in sucrose gradients showed that the ligand was sequentially associated with organelles banding at 1.14, 1.17 and 1.21 g/ml. At 9-12 min after intravenous injection the ligand was in a degradative compartment, as indicated by the accumulation of acid-soluble radioactivity at 1.21 g/ml. A rapid transfer of ligand to the lysosomes was also indicated by the finding that a substantial proportion of the ligand could be degraded by incubating mitochondrial fractions prepared 12 min after intravenous injection of the ligand. The results indicate that FSA is very rapidly internalized and transferred through an endosomal compartment to the lysosomes. The endosomes are gradually converted into lysosomes between 9 and 12 min after injection of FSA. The rate-limiting step in the intracellular handling of 125I-TC-FSA is the degradation in the lysosomes.

Animals↗
PubMed1989

Uptake of retinyl ester in HL-60 cells via the low-density-lipoprotein-receptor pathway.

Newly absorbed retinol is transported in association with chylomicrons and their remnants. In addition, after intake of high doses of retinol, significant amounts are also found in low-density lipoprotein (LDL). As both chylomicron remnants and LDL may be taken up by cells via the LDL receptor, and retinoids inhibit proliferation of some leukaemic cells, we have studied the uptake of retinol in leukaemic cells via the LDL-receptor pathway. HL-60 cells contain saturable binding sites for LDL. The binding of LDL to its receptor has a dissociation constant of about 3.2 x 10(-9) M, and the number of receptors per cell was calculated to be about 2700. Uptake of 125I-LDL by HL-60 cells was increased 2-fold by preincubating the cells with mevinolin. The presence of specific receptors for LDL on HL-60 cells was further confirmed by the finding that exogenous LDL cholesterol was able to up-regulate the ACAT (acyl-CoA: cholesterol acyltransferase) activity of HL-60 cells. We then tested the uptake of retinyl ester in leukaemic cells via the LDL-receptor pathway. HL-60 cells were incubated with LDL or chylomicron remnants labelled with [3H]retinyl palmitate. Uptake of retinyl ester associated with both LDL and chylomicron remnants was observed. Furthermore, the presence of excess LDL decreased the uptake by 75-100%, supporting the hypothesis that the uptake of retinyl ester occurred via the LDL receptor in HL-60 cells.

Cell Line↗
PubMed1989

Retinol and retinyl esters in patients with alcoholic liver disease.

Liver retinoid levels and the retinyl esters were examined in liver biopsy specimens from 70 patients with alcoholic and nonalcoholic liver diseases. There was a wide variation in the liver retinoid levels. The liver retinoid level was statistically significantly lower in 15 patients with alcoholic liver disease and a depressed Normotest (NT) value of less than 65% compared with patients with alcoholic liver disease and a normal NT value of greater than 65% (P less than 0.01). The mean serum retinol level in patients with alcoholic cirrhosis was 0.68 +/- 0.38 mumol/l compared with 1.99 +/- 1.14 mumol/l in patients with alcoholic fatty liver (P less than 0.03). The relative amount of retinyl oleate was increased in the alcoholic fatty liver compared with the nonalcoholic fatty liver (P less than 0.001).

Adult↗