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Biomedical subjects

B Borgström

Publications and source records attributed to B Borgström.

At least 37 records · Page 2Linked to original sources
PubMed1989

Facial growth and morphology in long-term survivors after bone marrow transplantation.

A roentgen cephalometric investigation was used to study facial growth and morphology in 17 children who had undergone bone marrow transplantation (BMT) because of acute leukaemia and aplastic anaemia. The ages at BMT varied from 1.0 to 12.9 years. Preoperative treatment included high doses of cyclophosphamide and in children with acute leukaemia also 10 Gy total body irradiation (TBI). The median observation period following BMT was 3.9 years. The control group comprised 85 age and sex matched healthy children. In comparison to the controls, all linear measurements studied were found to be significantly diminished in children conditioned with TBI. For variables describing vertical dimensions, the degree of reduction appeared to be associated with the patients' ages at the time of irradiation. It was concluded that the disturbance in dental development, which is also a consequence of TBI, could be partly responsible for this association. Children who were not conditioned with TBI exhibited no significant differences when compared to controls in respect of the variables studied.

Bone Marrow Transplantation↗
PubMed1988

Mode of action of tetrahydrolipstatin: a derivative of the naturally occurring lipase inhibitor lipstatin.

Tetrahydrolipstatin is a specific lipase inhibitor derived from lipstatin, a lipid produced by Streptomyces toxytricini. In addition to pancreatic lipase, it is shown in the present study that tetrahydrolipstatin also inhibits human gastric lipase, carboxyl ester lipase (cholesterol esterase) of pancreatic origin and the closely related bile-salt-stimulated lipase of human milk. It does not inhibit the exocellular lipase from Rhizopus arrhizus or a lipase recently isolated from Staphylococcus aureus. In the presence of a water-insoluble substrate, such as tributyrin, the inhibition has the characteristics of an irreversible inactivation of the uncompetitive type, thus indicating that an enzyme.substrate.inhibitor complex is formed, which cannot undergo further reaction to yield the normal product. This reaction probably takes place at the aqueous/oil interface of the substrate. In aqueous solution, in the absence of substrate, the inhibition of carboxyl ester lipase by tetrahydrolipstatin has the characteristics of being reversible, and finally becomes of a temporary nature analogues to the trypsin-trypsin inhibitor system. It is suggested that an enzyme-inhibitor complex of an acyl-enzyme type is formed that is slowly hydrolysed, with water as the final acceptor, leaving an intact enzyme and an inactive form of the inhibitor. The enzyme thus consumes the inhibitor, which undergoes a chemical conversion, as indicated by a change in mobility in an appropriate thin-layer chromatographic system, indicating an increase in hydrophilicity. Evidence is presented that the reaction product is an acid and that the functional group of tetrahydrolipstatin is the beta-lactone reacting with the active site of the enzyme.

Bile Acids and Salts↗
PubMed1988

Concerted action of human carboxyl ester lipase and pancreatic lipase during lipid digestion in vitro: importance of the physicochemical state of the substrate.

The pancreatic enzyme carboxyl ester lipase (CEL) has been shown to hydrolyse a large number of different esters, including triacylglycerols, cholesteryl esters and retinyl esters with an absolute requirement for bile salts. Some of the lipids that are substrates for CEL can also be hydrolysed by pancreatic lipase. In order to investigate the relative roles of human CEL and pancreatic lipase, the two enzymes were incubated on a pH-stat with isotope-labelled lipid substrate mixtures in physicochemical forms resembling the state of the dietary lipids in human intestinal contents. In the first set of experiments, cholesteryl oleate (CO) and retinyl palmitate (RP) were solubilised in an emulsion of triolein (TO) stabilised by egg phosphatidylcholine and bile salts. Lipase (always added together with its cofactor, colipase) hydrolysed TO, with monoolein and oleic acid as end-products, whereas CEL alone could not hydrolyse TO in the presence of phosphatidylcholine (PC). Lipase alone did not hydrolyse CO or RP, but CEL did hydrolyse these esters if lipase was present. Release of [3H]glycerol from labelled TO increased only slightly if CEL was added compared to lipase alone, suggesting that monoolein hydrolysis was slow under these conditions. In the second set of experiments, CO and RP were dissolved in bile salt/monoolein/oleic acid dispersions with varying bile salt concentrations. CEL hydrolysed CO and RP more rapidly in a system with a high bile salt concentration containing mixed micelles than in a system with a low bile salt concentration, where the lipids were dispersed in the form of mixed micellar and non-micellar aggregates; both types of aggregate have been reported to exist in human intestinal contents. In conclusion, these data suggest that the main function of CEL under physiological conditions is to hydrolyse cholesteryl and retinyl esters, provided that the triacylglycerol oil phase is hydrolysed by pancreatic lipase, which probably causes a transfer of the substrate lipids of CEL from the oil emulsion phase to an aqueous bile salt/lipolytic product phase. Depending on the bile salt/lipolytic product ratio, the substrate will reside in either micellar or non-micellar lipid aggregates, of which the micellar state is preferred by CEL.

Bile Acids and Salts↗
PubMed1988

Growth and growth hormone in children after bone marrow transplantation.

Growth and growth hormone (GH) were investigated every year in 24 children after allogeneic bone marrow transplantation (BMT) for severe aplastic anemia (SAA) or leukemia. Conditioning included total body irradiation (TBI) in all cases of leukemia. The young leukemic children grew poorly. At 4 years after BMT, the mean standard deviation score for attained height had decreased from 0 to -1.73. GH deficiency was diagnosed with provocation tests. Three years after BMT, 10/18 children had a subnormal response. Ten children were further investigated with 24-hour GH profiles. Children with SAA had normal growth and GH levels. TBI seemed to be the major factor responsible for impaired growth.

Adolescent↗
PubMed1987

Factors regulating the formation of chylomicrons and very-low-density lipoproteins by the rat small intestine.

The aim of this study was to investigate how the relationship between chylomicron and very-low-density lipoprotein (VLDL) transport of fatty acid into lymph was affected by the total amount of lipid transported via the intestinal lymphatics in the rat. Two different experimental conditions were employed. First, intestinal lymph fistula rats were infused with four different levels of [3H]oleic acid (15, 30, 60 and 120 mumol per h) at a constant rate for 8 h. Lymphatic transport of [3H]oleic acid via chylomicrons and VLDLs was measured in lymph collected during the seventh h. Within the dose range studied chylomicron increased exponentially, while the output in VLDL reached a plateau at a total lymph [3H]oleic acid output of approx. 60 mumol/h. A linear regression analysis of the ln(chylomicron/VLDL) versus the total output in lymph yielded a coefficient of correlation of 0.95. Second, we utilized the fact that intraduodenal infusion of the nonionic detergent Pluronic L-81 (L-81) inhibits chylomicron transport and that this inhibition is reversed by the cessation of L-81 infusion (unblocking). A linear regression analysis of the ln(chylomicron/VLDL) versus total lymph [3H]oleic acid output during the first 4 h of unblocking gave a coefficient of correlation of 0.79. Statistical analysis of the regression equations from the two experiments showed that for the same lymphatic [3H]oleic acid output, the chylomicron/VLDL ratio was significantly lower in the L-81 experiment, indicating that the relative rates of formation of chylomicron to VLDL were different under these two experimental conditions. However, the principal pattern was the same, i.e., chylomicron production increased, while VLDL production became saturated when the amount of oleic acid transported to the lymph was increased.

Animals↗
PubMed1987

Deconjugation of bile salts: does it occur outside the contents of the intestinal tract in the rat?

Several different methods have been applied to measure the extent of bile salt deconjugation (deamidation), if any, outside the gastro-intestinal tract of the rat. A breath test has been applied to the rat using peroral or intravenous administration of cholyl-glycine-1-14C. Results for normal rats have been compared with rats with a continuous recirculation of bile to a tail vein. Bile salts labelled with 2,4-3H in the sterol moiety and conjugated with glycine-1-14C have been infused in rats and recirculated via a bile duct tail-vein shunt. The 3H:14C ratio in the bile has been used as an indication of deconjugation. In these experiments the radioactivity pattern of the bile salts has been determined after thin-layer chromatography. Different labelled bile salts have also been infused intraperitoneally and the composition of bile secreted through bile fistulae studied. In none of these experiments, in which the gastro-intestinal content was bypassed and a return of bile salts to the liver in the physiological range ensured, was any deconjugation of glycine-conjugated bile salts observed. When the liver, however, was stressed by anaesthesia and the intraportal infusion of deoxycholyl-2,4-3H-glycine in unphysiological levels, deconjugation occurred as indicated by the appearance in bile of labelled taurine conjugates. In these rats the dose of deoxycholylglycine was clearly toxic as evidenced by partial or complete cholestasis and eventually death of the animal.

Animals↗
PubMed1987

Deconjugation of glycine-amidated bile salts does not occur in germfree rats.

After oral administration to germfree rats of cholyl-glycine-1-14C, deoxycholyl-glycine-1-14C and nor-ursocholyl-glycine-1-14C no significant amounts of 14CO2 are expired. This indicates that these bile salts are not significantly deamidated under physiological conditions in the rat organism outside the gastro-intestinal tract.

Administration, Oral↗
PubMed1986

Effects of cholic acid, 7 beta-hydroxy- and 12 beta-hydroxy-isocholic acid on bile flow, lipid secretion and bile acid synthesis in the rat.

The effects of three epimeric trihydroxy-cholanoic acids, cholic acid (C), 7 beta-hydroxy-(7 beta) and 12 beta-hydroxy-(12 beta) isocholic acids on bile flow, lipid secretion, bile synthesis and bile micellar properties were studied in the rat with a bile fistula. The bile salts were infused intraduodenally starting 72 hours after cannulation when endogeneous bile salt synthesis had plateaued after the bile salt pool was drained. The bile salts were infused at two levels approximately 2 and 4 mumol min-1 kg-1. All three bile salts were absorbed and secreted almost quantitatively into the bile. Cholic acid was secreted in the conjugated form, 7 beta conjugated to approximately 60% and 12 beta completely in the unconjugated form. The bile salts did not undergo any significant biotransformations during the one passage from the intestine through the liver. Bile flow increased from the preinfusion level for all three bile salts infused in the order 7 beta greater than 12 beta greater than C. The bile flow increased linearly with bile salt secretion more for 7 beta than for C and 12 beta. Infusion of C increased the secretion into bile of phospholipid (PL) and cholesterol (CH) over the preinfusion values. Infusion of 7 beta as well as 12 beta resulted in a parallel decrease in the secretion of PL as well as CH compared to the preinfusion values. The infusion of C and 7 beta at the two levels used decreased the secretion of newly synthesized bile salt below the control level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Metabolism of cholate, 7 beta-hydroxy- and 12 beta-hydroxy-isocholates in the rat.

The three epimeric trihydroxy bile salts cholate (C), 7 beta-hydroxy-(7 beta) and 12 beta-hydroxy-(12 beta) isocholate were fed to rats by intubation or in the diet. All three bile salts were well absorbed 7 beta greater than C greater than 12 beta and underwent heavy biotransformations in the enterohepatic circulation 12 beta greater than 7 beta C. The result is a low concentration of unchanged administered bile salt in the bile salt pools, 12 beta less than 7 beta less than C, the percentage figures being 3, 20 and 35%, respectively, after 7 days feeding. In spite of this, the composition of the bile changes, less phospholipid and cholesterol being excreted in the bile per mumol bile salt after feeding, 7 beta and 12 beta compared to C. No significant increase in the faecal fat was seen in rats fed the beta-hydroxy bile salts. Only minor amounts of the radioactivity from the beta-hydroxy bile salts were secreted into the urine, and no more when compared to C.

Animals↗
PubMed1986

Effects of feeding ursocholic acid to germfree rats.

Germfree rats were fed 24-14C-ursocholic acid (UC) mixed into the diets for 10 days. The bile was then drained by cannulation for 6 hours to collect the bile salt pool. No biotransformation of the labelled UC occurred and it constituted approximately equal to 75% of an enlarged bile salt pool. Less phospholipid and cholesterol were secreted into the bile per mumol bile salt compared to normal rats. The critical micellar concentration (CMC) of the bile was determined by equilibrium dialysis and found to be increased. Faecal excretion of labelled triolein added to the diet was unaffected by feeding ursocholic acid. Excretion of 14C-octadecane and 14C-cholesterol increased significantly under the same conditions. Ursocholic acid feeding thus resulted in a selective malabsorption of octadecane and cholesterol.

Animals↗
PubMed1984

One-step purification of procolipase from human pancreatic juice by immobilized antibodies against human colipase86.

Purified antibodies to human colipase86 were coupled to CNBr-activated Sepharose 4B. The immunoadsorption column thus obtained was used to purify procolipase from human pancreatic juice in one step by immunoaffinity chromatography. A single form of procolipase was obtained, having similar biological properties as previously characterized procolipases from horse and pig. The sequence of the N-terminal propeptide was determined to be Ala-Pro-Gly-Pro-Arg. In bovine, equine and porcine procolipases the corresponding N-terminal sequence is Val-Pro-Asp-Pro-Arg.

Amino Acids↗
PubMed1984

The primary sequence of human pancreatic colipase.

The amino acid sequence of an activated colipase purified from human pancreas was determined. The protein consists of a single polypeptide chain of 86 amino acids (human colipase86) and has a molecular weight of 9289. The sequence was determined by automated Edman degradation of the reduced and S-carboxymethylated protein and of two CNBr peptides. Sequence determination of porcine procolipase II was also performed, which showed that in the original sequence determination apparently two residues were missed. These residues were determined to be a leucine at position 37 and a serine in position 50. For comparison with porcine and equine procolipases, the residues composing human colipase are numbered from 6 to 91. No human procolipase has been isolated so far. The colipases from man, pig, horse and chicken show a high degree of homology: human colipase differs from the other proteins by substitutions of 19 (porcine), 24 (equine A) and 21 (equine B) residues, respectively.

Amino Acid Sequence↗
PubMed1983

Evolutionary studies on pancreatic colipase.

In this evolutionary study the following criteria have been used to prove the existence of colipase: 1. It restores the activity of human and porcine pancreatic lipase inhibited by bile salt. 2. It cross-reacts with antisera to human and porcine colipases. 3. Its restoration of lipase activity, inhibited by bile salt, in the tributyrin assay system, is prevented by antiserum to colipase. 4. It is a heat-stable, low-molecular-weight protein (molecular weight about 10 000 by gel-filtration). The occurrence of colipase has been verified in the exocrine pancreatic cells from hagfish (Myxine glutinosa), ratfish (Chimaera monstrosa), rayfish (Raja radiata). Greenland shark (Somnius microcephalus) and dogfish (Squalus acanthius). No colipase activity could be found in the gastric juice of crayfish (Pacifastacus leniusculus). These results indicate that colipase envolved in the vertebrates before the organized exocrine pancreatic gland and occurred simultaneously with the bile salts/bile alcohols.

Animals↗