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Biomedical subjects

T Berg

Publications and source records attributed to T Berg.

At least 289 records · Page 16Linked to original sources
PubMed1983

Transport of cholesterol.

.ur current model for cholesterol transport is summarized in Figure 10. In this figure we have put together the various steps in cholesterol transport that were described previously in this review. Under normal conditions, cholesterol metabolism and transport are well regulated. If the transport system is overloaded for a long time, however, hypercholesterolemia caused mainly by increased plasma LDL may develop in several species, including humans. Under such circumstances reverse transport of cholesterol may also fail, giving rise to deposits of cholesterol. Tissue macrophages may be responsible for this lipid accumulation, because receptor-mediated (adsorptive) endocytosis of lipoprotein-associated cholesterol in these cells is not under negative-feedback control. The deposits are mainly found in tissues poorly supplied with blood and lymph: the skin, tendons, the cornea, and arteries. Overload of cholesterol transport may be the result of too much fat and cholesterol in the diet, giving rise to cholesterol-rich lipoproteins from the gut and to increased production of liver (formula; see text) VLDL, which in humans ends up as LDL. In many individuals, however, no hypercholesterolemia is seen, even after eating large amounts of a "western" diet for decades; others may develop increased LDL on a relatively "prudent" diet. Obviously many of the factors and mechanisms in cholesterol transport are influenced by genetic factors. Although studies of several inborn errors of lipid metabolism have given information about some mechanisms, the quantitatively more important differences in genetic patterns, which determine whether or not a western diet will result in hyperlipidemia, are not well known. Perhaps studies of different forms of apoB and apoE and of HDL subgroups and hyper-alpha-lipoproteinemia will explain why certain individuals develop hypercholesterolemia and premature atherosclerosis. All the recent information related to cholesterol metabolism and transport gives rise to new questions. There are many problems of interest for future research: What are the metabolic differences between the apoB produced in the liver and that produced in the gut? To what extent is the protein moiety of LDL modified in the plasma of blood and lymph and in interstitial tissue? Are such modifications important to whether LDL uptake goes through the classic LDL pathway or through the macrophage (i.e., scavenger?) pathway? Are some changes in apoB important for liver recognition of LDL?(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

Intracellular transport and degradation of 125I-Labelled denatured serum albumin in isolated nonparenchymal rat liver cells.

The intracellular movement, following uptake of 125I-labelled denatured serum albumin into nonparenchymal liver cells, was followed by means of subcellular fractionation. Isolated nonparenchymal rat liver cells were prepared by means of differential centrifugation. The cells were homogenized in a sonifier and the cytoplasmic extract subjected to isopycnic centrifugation in a sucrose gradient. The intracellular movement of the labelled albumin was followed by comparing the distribution profile of radioactivity in the sucrose gradient with those of marker enzymes for plasma membrane and lysosomes. The distribution profiles for radioactivity after the cells had been exposed to the labelled denatured albumin for different time periods indicated that the radioactivity was first associated with subcellular fractions of lower modal densities than the lysosomes. With time of incubation the radioactivity moved towards higher densities. After prolonged incubations in the absence of extracellular labelled denatured albumin the radioactivity peak coincided with that of the lysosomal marker beta-acetylglucosaminidase. When the cells were treated with the lysosomal inhibitor leupeptin, degradation of the labelled albumin was decreased, resulting in a massive intracellular accumulation of radioactivity. The radioactivity peak coincided with the peak of activity for the lysosomal marker beta-acetylglucosaminidase, suggesting lysosomal degradation.

Animals↗
PubMed1982

Binding of calcium ions to the isolated asialo-glycoprotein receptor. Implications for receptor function in suspended hepatocytes.

The binding of calcium ions by the isolated asialoglycoprotein receptor of hepatocytes and the inter-relationship between the calcium ion concentration and receptor function have been studied. The isolated receptor binds calcium ions only in the presence of asialoglycoprotein. The asialo-glycoprotein receptor complex binds 4 calcium ions; the binding exhibits marked positive cooperativity, and the association constant at half-saturation of the binding sites was of the order of 10*5) M-1 as determined from a Hill plot. The isolated receptor was almost saturated at a calcium ion concentration of 0.1 mM. The binding capacity of isolated hepatocytes for asialo-glycoproteins increased, however, even when the calcium concentration was increased above this level. This may be explained by the exposure of increasing numbers of functional receptors on the surface of the cell with increasing membrane potential, and this explanation is supported by analogous observations in the presence of 5 mM La3+.

Animals↗
PubMed1982

Uptake and degradation of desialylated luteinizing hormone by suspended hepatocytes.

The uptake and degradation of desialylated human luteinizing hormone (asialo-LH) in suspended hepatocytes have been studied. Asialo-LH was taken up by the asialo-glycoprotein receptor at a rate which was somewhat lower than that of asialo-fetuin. The rate constants and equilibrium binding parameters were similar, but the rate of dissociation of the receptor-ligand complex was higher in the case of asialo-LH. The uptake was influenced by heterogeneity of the asialo-LH preparation. Degradation of endocytosed asialo-LH took place in the lysosomes. After fractionation of the cells by isopycnic centrifugation in a sucrose gradient, partially degraded asialo-LH (precipitable with trichloracetic acid, but not with antibody) was found in the fractions containing endocytic vesicles, but not in the lysosomal fractions, indicating that the proteolysis of asialo-LH was initiated in the endocytic vesicles.

Animals↗
PubMed1982

Effects of local anesthetics and related compounds on the endocytosis and catabolism of asialo-glycoproteins in isolated hepatocytes.

The effects of local anesthetics, including procaine and dibucaine, and some related amine compounds, such as dansyl-cadaverine, were studied with respect to their effects on the uptake and degradation of asialo-glycoproteins in isolated hepatocytes. 0.5 mM of either dibucaine or dansyl-cadaverine reduced the rates of uptake to 18-19% of control value; other amines were less effective. Dibucaine and dansyl-cadaverine both acted by reducing the surface binding capacity of the cells as well as by reducing the rate of internalization of surface-bound asialo-glycoprotein. All of the compounds that affected the uptake, including dansyl-cadaverine, also reduced the rate of degradation. This effect could be studied separately from their effect on uptake. The concentrations that were required in order to reduce degradation were, in general 0.5-0.25 of those which caused a reduction in the uptake. Even though dibucaine, lidocaine and dansyl-cadaverine were found to accumulate in the lysosomes, it was concluded from studies with isopycnic centrifugation in sucrose gradients that all three compounds inhibited the rate of transfer of endocytosed protein from endocytic vesicles to lysosomes. This effect could be due to a reduced rate of fusion between endocytic vesicles and lysosomes.

Anesthetics, Local↗
PubMed1982

In vivo uptake of chylomicron [3H]retinyl ester by rat liver: evidence for retinol transfer from parenchymal to nonparenchymal cells.

We have studied hepatic uptake of chylomicron retinyl ester. Chylomicrons were obtained from intestinal lymph of rats that were given retinol in groundnut oil by intraduodenal injection. When lymph was injected intravenously into normal rats, the radioactivity was cleared from blood with t1/2 approximately equal to 10 min. Retinyl ester was taken up initially by the liver, which, after 30 min, contained 80-90% of the radioactivity injected. Initially, most of the radioactivity was in hepatocytes, but after 30 min it disappeared from these cells and reappeared in nonparenchymal liver cells. After 2 hr these cells contained more radioactivity than the hepatocytes. When lymph was injected into vitamin A-deficient rats or rats given vitamin A in the form of retinoic acid, the plasma clearance and initial hepatic uptake of radioactivity were similar to that found in control animals. However, the nonparenchymal cells in these animals did not accumulate radioactivity. The current data suggest that vitamin A (in chylomicron remnants) is taken up initially by hepatocytes and then is released from these cells and delivered mainly to nonparenchymal liver cells in normal animals. In vitamin A-deficient rats, the vitamin is transferred from the hepatocytes to extrahepatic tissues.

Animals↗
PubMed1982

Quantitation of binding and subcellular distribution of Clostridium perfringens enterotoxin in rat liver cells.

Binding of enterotoxin from Clostridium perfringens type A was studied in suspensions of parenchymal and nonparenchymal cells from rat liver. In hepatocytes, 1.5 X 10(6) specific binding sites per cell with an association constant of 3.2 X 10(6) M-1 were found. About 1% of the added toxin was nonspecifically bound to the hepatocytes. At concentrations of toxin below 0.1 micrograms/ml, 80% of the toxin density of 7 X 10(6) cells per ml. Binding did not increase after the cells became permeable to the toxin. Subcellular fractionation in a sucrose gradient produced no evidence for binding to parts of the cell other than the plasma membrane. The degree of binding to nonparenchymal cells was less than 10% of the binding to hepatocytes.

Animals↗
PubMed1982

Clinical studies of a purified timothy pollen extract: desensitization therapy with a purified timothy pollen preparation compared to a crude timothy pollen extract. II. Results of the tests in vitro and their relation to symptoms and tests in vivo.

Perennial desensitization therapy was given during a period of 3.5 years to 40 children allergic to grass pollen allergens. 20 patients were treated with a crude and another 20 with a purified timothy pollen extract. 8 children served as untreated controls. The concentration of total and specific IgE in the treated groups covaried with those in the control group. Neither a suppression of the seasonal booster effect nor a suppression of IgE synthesis attributable to the treatment was found. The rise of timothy-specific "blocking' IgG antibodies was more pronounced in the group treated with the purified extract than in the group treated with the crude extract. A significant difference was found only after 3.5 years of treatment. The amplitude of rise of IgG antibodies correlated significantly with the effect of the treatment as judged by repeated conjunctival titration test. The results suggest that a good IgG response is an indication of successful therapy and that a better IgG response may be achieved with purified allergen extracts.

Adolescent↗
PubMed1982

Salbutamol in the treatment of asthmatic children. A comparison of oral and inhalation therapy alone and in combination.

In 10 children with asthma and reversible bronchial obstruction the effect on lung function (VC, FVC and FEV1) of salbutamol was tested comparing oral administration, inhalation or a combination of both. The oral treatment was carried out as a randomized double-blind salbutamol-placebo cross-over study followed by inhalation of salbutamol in all patients. In agreement with previous findings in adults, the study showed a significant increase of FEV1, FVC and VC (P less than 0.005) after oral salbutamol. Combined oral and inhalation medication of salbutamol gave a significantly higher increase of FEV1, VC (P less than 0.01) and FVC (P less than 0.05) when compared with oral therapy only. Compared with salbutamol inhalation only, the combined therapy gave a significantly higher FEV1 (P less than 0.01). The relatively high oral dose used produced no side effects.

Administration, Oral↗
PubMed1981

Evidence for in vivo hepatic uptake of a galactose-terminated glycoprotein in fish (Salmo alpinus L.).

125I-labelled asialofetuin injected intravenously into chars (Salmo alpinus L.) was cleared from the blood with a half-time of approx. 60 min. The injected asialofetuin was found to be accumulating in the liver when different organs were dissected out at various time points after the injection. 125I-labelled fetuin was not concentrated in the liver, and the uptake of 125I-labelled asialofetuin was almost completely inhibited by simultaneously injecting an excess unlabelled asialofetuin, indicating a specific uptake mechanism for the galactose-terminated glycoprotein in char liver. Denatured human serum albumin was not taken up by the liver, but was recovered in the kidneys, suggesting that the liver in char is devoid of macrophages. It therefore seems reasonable to assume that the injected 125I-labelled asialofetuin is taken up by the parenchymal cells of the char liver.

Animals↗
PubMed1981

Uptake and 25-hydroxylation of vitamin D3 by isolated rat liver cells.

The physiological roles played by hepatocytes and nonparenchymal cells of rat liver in the metabolism of vitamin D3 have been investigated. Tritium-labeled vitamin D3 dissolved in ethanol was administered intravenously to two rats. Isolation of the liver cells 30 and 70 min after the injection showed that vitamin D3 had been taken up both by the hepatocytes and by the nonparenchymal liver cells. The relative proportion of vitamin D3 that accumulated in the nonparenchymal cells increased with time. Perfusion of the isolated rat liver with [3H] vitamin D3 added to the perfusate confirmed the ability of both cell types to efficiently take up vitamin D3 from the circulation. By a method based on high pressure liquid chromatography and isotope dilution-mass fragmentography it was found that isolated liver cells in suspension had a considerable capacity to take up vitamin D3 from the medium. About 2.5 fmol of vitamin D3 were found to be associated with each hepatocyte or nonparenchymal cell after 1 h of incubation. 25-Hydroxylation in vitro was found to be carried out only by the hepatocytes. The rate of hydroxylation was about the same whether the cells were isolated from normal or rachitic rats (3.5 and 4 pmol of 25-hydroxyvitamin D3 formed per h per 10(6) cells, respectively). The possibility that the nonparenchymal cells might serve as a storage site for vitamin D3 in the liver is discussed.

Animals↗
PubMed1981

The binding of high density lipoproteins to isolated rat hepatocytes.

The association of 125I-labelled rat high density lipoproteins (125-I-HDL) to suspended rat hepatocytes was studied at 4 degrees C. 125 I-HDL associated to isolated hepatocytes by two processes-one of high and one of low affinity. The cell-association of 125I-HDL exhibited saturation kinetics and was inhibited to varying degrees with both rat and human lipoproteins such as VLDL, LDL and HDL but not by lipoprotein deficient serum or asialo-fetuin. The cell-association of 125I-HDL did not require divalent cations and could be reduced by pronase treatment of the cells. The binding site was clearly different from the receptor for LDL in extrahepatic cells since heparin and apolipoprotein E did not compete and cholesterol ester labelled HDL. The number of binding sites for HDL at 4 degrees C was 2.2 X 10(6) per cell and the association constant (Ka) 8.2 X 10(6) (mol/l)-1. Experiments with HDL labelled with [3H] cholesterol by means of lecithin: cholesterol acyltransferase (LCAT, EC 2.3.1.43) in the cholesterol ester moiety suggested that the same mechanism was responsible for the cell-association of HDL prepared this way.

Animals↗
PubMed1981

Effect of leupeptin on the intracellular degradation of asialofetuin in isolated rat hepatocytes.

The effect of the protease inhibitor leupeptin on the intracellular distribution of [14C]-sucrose-asialofetuin in isolated rat hepatocytes was investigated. Leupeptin had no effect on the uptake but reduced the degradation of asialofetuin. Fractionation of hepatocytes by isopycnic centrifugation in sucrose gradients indicated that prolonged treatment with leupeptin inhibited the uptake of asialofetuin into the lysosomes. Therefore, leupeptin inhibits degradation of asialofetuin both by inhibiting intralysosomal proteolysis and transport of endocytosed asialofetuin to the lysosomes.

Animals↗
PubMed1981

Allergological aspects of atopic eczema in children.

Food allergy is often, but far from always, of importance in atopic dermatitis in children. Positive findings in the allergological diagnosis are more common in children who also have other atopic symptoms than their eczema. The results of the allergological diagnosis are often hard to evaluate and sometimes misleading. Skin tests are only of limited value in food allergy. The importance of circulating reagins to food varies with respect to the kind of food, the age of the child and the antibody titre. It is therefore important to consider the results of the skin test and RAST together with the patient's history. Provocation tests may sometimes be necessary. It can also be necessary to prescribe so-called elimination diet for some time to children with atopic dermatitis. The judgement of the influence on the child's eczema of such an elimination diet needs experience and perhaps also repeated observations.

Child↗