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Biomedical subjects

G Bengtsson

Publications and source records attributed to G Bengtsson.

At least 55 records · Page 3Linked to original sources
PubMed1981

Natural history of patients with untreated liver metastases from colorectal cancer.

One hundred fifty-five patients, laparotomized because of colorectal cancer, were retrospectively evaluated with special attention given to the natural course of untreated synchronous liver metastases. The median survival time for patients with synchronous liver metastases was 4.5 months. The survival time was mainly influenced by the extent of tumor involvement in the liver. Patients with elevated levels of serum-alkaline phosphatase at the time of operation had a significantly shorter survival time than those with normal values. Serum alkaline phosphatase levels are a good indication of prognosis. The incidence of synchronous liver metastases was 16 percent. This low rate is partly explained by the development of metachronous liver metastases in five patients within 1 year. Comparison with previous reports, often more than 10 years old, reveals that the poor prognosis of patients with untreated liver metastases from colorectal cancer has remained unchanged.

Adult↗
PubMed1981

Lipoprotein lipase: modification of its kinetic properties by mild tryptic digestion.

Mild tryptic digestion of lipoprotein lipase cleaved its polypeptide chain in the middle, but the pieces were held together by disulphide bonds. The modified enzyme retained its ability to bind to heparin and to anionic detergents and on gel filtration it eluted in a similar position as the native enzyme does. It also retained essentially full activity against soluble substrates. Thus, the overall physico-chemical properties of the enzyme were not markedly changed and its active site remained intact after treatment with trypsin. The activity of the modified enzyme against long-chain acylglycerols and phospholipids was, however, much reduced. With some emulsions, the decreased activity could be ascribed in part to a decreased ability of the modified enzyme to bind to the emulsion droplets. Under these conditions apolipoprotein CII partially restored both binding and activity. With a lysophosphatidylcholine-triacylglycerol emulsion the modified enzyme adsorbed almost completely to the emulsion droplets, but its activity was nonetheless very low. Thus, tryptic cleavage interfered with the ability of the enzyme to become properly orientated at the interface. With this emulsion apolipoprotein CII enhanced the activity of the native enzyme fourfold but the activity of the trypsin-treated enzyme 30-fold, so that the activity of the modified enzyme became almost as high as that of the native enzyme. It is concluded that apolipoprotein CII enhances the activity of lipoprotein lipase by stabilizing an effective orientation/conformation of the enzyme at the interface. This effect became more marked when the ability of the enzyme itself to attain this form had been reduced by tryptic cleavage.

Animals↗
PubMed1980

Interaction of lipoprotein lipase with native and modified heparin-like polysaccharides.

1. Lipoprotein lipase (EC 3.1.1.34), which was previously shown to bind to immobilized heparin, was now found to bind also to heparan sulphate and dermatan sulphate and to some extent to chondroitin sulphate. 2. The relative binding affinities were compared by determining (a) the concentration of NaCl required to release the enzyme from polysaccharide-substituted Sepharose; (b) the concentration of free polysaccharides required to displace the enzyme from immobilized polysaccharides; and (c) the total amounts of enzyme bound after saturation of immobilized polysaccharides. By each of these criteria heparin bound the enzyme most efficiently, followed by heparan sulphate and dermatan sulphate, which were more efficient than chondroitin sulphate. 3. Heparin fractions with high and low affinity for antithrombin, respectively, did not differ with regard to affinity for lipoprotein lipase. 4. Partially N-desulphated heparin (40-50% of N-unsubstituted glucosamine residues) was unable to displace lipoprotein lipase from immobilized heparin. This ability was restored by re-N-sulphation or by N-acetylation; the N-acetylated product was essentially devoid of anticoagulant activity. 5. Partial depolymerization of heparin led to a decrease in ability to displace lipoprotein lipase from heparin-Sepharose; however, even fragments of less than decasaccharide size showed definite enzyme-releasing activity. 6. Studies with hepatic lipase (purified from rat post-heparin plasma) gave results similar to those obtained with milk lipoprotein lipase. However, the interaction between the hepatic lipase and the glycosaminoglycans was weaker and was abolished at lower concentrations of NaCl. 7. The ability of the polysaccharides to release lipoprotein lipase to the circulating blood after intravenous injection into rats essentially conformed to their affinity for the enzyme as evaluated by the experiments in vitro.

Animals↗
PubMed1980

Lipoprotein lipase: some effects of activator proteins.

This paper considers how apolipoprotein CII from human plasma lipoproteins and T1 and T2 proteins from egg yolk lipoproteins stimulate the activity of lipoprotein lipase. These activator proteins stabilized the enzyme much more effectively than a thousandfold higher concentration of albumin did, indicating a direct interaction with the enzyme. The effects of the activators were seen also at 1 M NaCl. Thus, forces other than electrostatic are implicated. Centrifugation experiments showed that 125I-labeled lipase bound equally well to the emulsion droplets in the absence of activator protein as in its presence. This was true even under conditions when the activator caused a severalfold increase in the rate of hydrolysis. Thus, the activator makes enzyme at the interface more effective in hydrolysis. By optimizing the conditions it was possible to obtain almost as high rates of triglyceride hydrolysis in the absence as in the presence of activator. Thus, the main effect of the activator protein is probably not on a rate-limiting chemical step. Under most conditions, the rate of hydrolysis was much below optimal and activator increased it. This was always the case with phosphatidyl-choline/triglyceride emulsions, where the activator enhanced hydrolysis of both lipids. Other experiments showed that the activator enhanced triglyceride hydrolysis in the absence of phospholipids and phospholipid hydrolysis in the absence of triglycerides. It is suggested that interaction with activator orientates the enzyme and/or the lipid substrate for effective hydrolysis at the surface of lipoproteins/model substrates.

Animals↗
PubMed1980

Lipoprotein lipase. Mechanism of product inhibition.

The rate at which lipoprotein lipase hydrolyzes triglycerides in lipoproteins and in synthetic emulsions decreases sharply with the amount of products formed unless albumin is present. Three factors which contribute to this inhibition as follows. (a) The fatty acids and the monoglycerides formed on hydrolysis locate at the lipid-water interface of the emulsion and, since they are substrates for the enzyme, act as competitive inhibitors of triglyceride hydrolysis. (b) The enzyme forms complexes with fatty acids. Therefore, as fatty acids accumulate in the system some of the enzyme will be sequestered into enzyme-fatty acid complexes. Albumin can prevent formation of such complexes since it has a higher affinity for fatty acids than the enzyme has. (c) Activator proteins do not enhance triglyceride hydrolysis unless a fatty acid acceptor is present. The strong inhibition of the enzyme itself and the loss of lipolysis-stimulating effects of activator proteins provide a feed-back regulation of the action of the lipase on lipoproteins at the capillary endothelium, ensuring that products are not generated more rapidly than they are utilized by the tissue.

Albumins↗
PubMed1980

Possible significance of changes in the energy metabolism for the release of liver lactate dehydrogenase and for the uptake and incorporation of [14C]-orotic acid into liver ribonucleic acid after partial hepatectomy.

The mouse liver revealed no increased incorporation of [14C]-orotic acid into either the total acid-soluble fraction, the uridine triphosphate or the RNA at 6 and 24 h after partial hepatectomy. In regenerating mouse and rat liver, the concentration of adenosine triphosphate was decreased 15-20% at 6 h, but was in the same range as that of the controls at 24 h. The adenosine monophosphate concentration of mouse liver increased 4-fold and 2-fold at these times after partial hepatectomy, respectively. The results indicate no direct relationship between the energy metabolism and the uptake and incorporation of orotic acid into RNA of regenerating liver. The activity of mouse plasma lactate dehydrogenase 5 (LDH 5) was increased 12-fold at 6 h and 5-fold at 24 h after partial hepatectomy. In rat, the LDH 5 activity was increased 2-fold at 6 h but was not different from that of the controls at 24 h. An increased leakage of LDH 5, possibly related to the decreased energy content of the liver, was thus revealed by the partially hepatectomized mice.

Adenine Nucleotides↗
PubMed1979

Guinea pig very low density lipoproteins are a good substrate for lipoprotein lipase.

In contrast to plasma from most other animals, guinea pig plasma causes little or no stimulation of lipoprotein lipase activity. Very low density lipoproteins (VLDL) isolated by ultracentrifugation of guinea pig serum caused a definite stimulation of lipase activity, whereas the infranatant inhibited the activity. Gel filtration in 5 M guanidinium hydrochloride of delipidated VLDL demonstrated that the activation was caused by a low molecular weight protein. The VLDL themselves were hydrolized at similar rates as human VLDL both by guinea pig and by bovine lipoprotein lipases. Thus, guinea pig VLDL contain an activator for lipoprotein lipase analogous to that in other animals and there is enough of the activator to support rapid hydrolysis of the VLDL lipids by the lipase.

Animals↗
PubMed1979

Rapid removal to the liver of intravenously injected lipoprotein lipase.

Lipoprotein lipase was purified from bovine milk and labeled with 125I. After intravenous injection to rats the labeled lipase rapidly disappeared from the blood. The initial half-life was about 1 min and more than 70% of the radioactivity was found in the liver at 10 min. 30 min after the injection about 10% of the injected radioactivity was present in acid-soluble form in blood, indicating that the enzyme had been rapidly degraded. Injection of asialofetuin, ribonuclease B or mannan in amounts known to block the hepatic receptors for glycoproteins with exposed galactose, N-acetylglucosamine or mannose residues did not retard the removal of the lipoprotein lipase. Thus, some other, as yet undefined, receptor is implicated. Lipoprotein lipase is known to bind to heparin and some related polysacchrides. Heparin injected before the enzyme delayed its removal and heparin injected after the enzyme caused an immediate increase in blood radioactivity, signifying return from tissues to blood of labeled enzyme. Lipoprotein lipase is present at the endothelium in several extrahepatic tissues and is rapidly turned over. Its presence in blood in appreciable amounts would cause a derangement of lipid transport. The efficient hepatic removal of the enzyme may thus serve an important physiological purpose in keeping the blood levels of this enzyme low.

Animals↗
PubMed1979

Colipase enhances hydrolysis of dietary triglycerides in the absence of bile salts.

This study explores how dietary lipids are digested when intraduodenal bile salts are low or absent. Long-chain triglycerides emulsified with phosphatidylcholine were found to be hydrolyzed very slowly by pancreatic lipase alone, as if the surface layer of phospholipids enveloping the triglycerides impeded the action of the enzyme. Colipase enhanced triglyceride hydrolysis severalfold, both when added before or after the lipase. Hydrolysis became even more rapid when the emulsion was first incubated with pancreatic phospholipase. Hydrolysis of long-chain triglycerides was also severely impeded when other proteins were added to the system, probably because they adsorbed to the oil-water interface of the emulsion droplets. It was previously known that bile salts can relieve such inhibition, presumably by desorbing the adsorbed proteins. Colipase was found to enhance hydrolysis severalfold in a dose-dependent manner even in the absence of bile salts, i.e., it could partially or completely relieve the inhibition depending upon the amount and the type of inhibitory protein added to the system. Prior exposure of a protein-coated triglyceride emulsion to another lipase also enhanced the rate at which pancreatic lipase could then hydrolyze the lipids. Most dietary triglycerides are probably presented for intestinal digestion in emulsions covered by proteins and/or phospholipids. These emulsions would be hydrolyzed slowly by pancreatic lipase alone. However, through the action of the lipase in stomach contents and of pancreatic phospholipase and through the lipolysis-promoting effects of collipase, these triglycerices can be rather efficiently hydrolyzed, even in the absence of bile salts.

Animals↗