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Biomedical subjects

B Borgström

Publications and source records attributed to B Borgström.

At least 19 recordsLinked to original sources
PubMed1995

Longitudinal study of adrenocortical function following allogeneic bone marrow transplantation in children.

Basal serum concentrations of cortisol, dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3,17-dione (A4) and 17 alpha-hydroxyprogesterone (17OHP) were measured yearly in children treated with bone marrow transplantation (BMT) with or without preceding total body irradiation (TBI). Age-matched controls were used for comparison. ACTH stimulation tests were performed in the patients before and after treatment. However, in the samples taken before BMT only cortisol was measured. Basal posttreatment cortisol levels were subnormal in TBI-treated boys (n = 14, aged 5-17 years at BMT) during the adrenarcheal period (7-14 years) but became normal afterwards. All other groups had normal cortisol values. Treatment neither affected basal levels nor the ACTH-induced increment (delta-value) of cortisol. In the boys treated with TBI, normal basal levels of 17OHP and adrenal androgens were found with the exception of decreased DHA levels in the postadrenarcheal boys. However, the delta-17OHP values and had an abnormal age relation and were significantly higher than in the patients not treated with TBI. In the patients not treated with TBI (6 boys aged 2-17 years) normal responses were found for 5 years or more after treatment. In female patients treated with TBI (n = 12, aged 1-16 years) circulating levels of DHA, DHAS and A4 were significantly decreased up to 5 years or more following treatment. It is concluded that after TBI, the cortisol homeostasis is maintained at the cost of reduced adrenal androgen secretion.

17-alpha-Hydroxyprogesterone↗
PubMed1994

Changes in craniofacial development induced by growth hormone therapy in children treated with bone marrow transplantation.

The effect of growth hormone (GH) treatment on craniofacial development was studied in nine children exhibiting low growth velocity after bone marrow transplantation (BMT). Comparisons were made with seven BMT children who had not received GH. Two groups of age- and sex-matched healthy children served as controls for the respective patient groups. After an average observation period of 3.5 years, the BMT children not treated with GH exhibited significantly reduced mandibular length and alveolar height (p < 0.01). The increase in mandibular length was only 30% of that found in healthy controls. Maxillary growth was less affected by BMT treatment. In the GH treated group, no significant differences were found in craniofacial growth increments compared with controls. Although exogenous GH therapy in this group of children did not induce a catch-up growth, it appears to have prevented further loss in growth potential.

Adolescent↗
PubMed1994

Thyroid function in children after allogeneic bone marrow transplantation.

Thyroid function was investigated in 35 children after allogeneic BMT. The study was longitudinal and all patients were followed for at least 5 years. Once a year TSH, T4, T3 and the TRH test were performed. Patients with severe aplastic anemia (n = 6) were transplanted without total body irradiation (TBI) and they had no detectable alterations in thyroid function. Patients with leukemia (n = 27) were conditioned with 10 Gy TBI in one fraction. The accumulated frequencies of thyroid dysfunction were 3 of 27 (11%) with high TSH and low T3 or T4 levels, and 10 of 27 (37%) with high basal TSH and normal T3 and T4 levels. An additional 11 of 27 (41%) had an exaggerated TSH response in the TRH test and normal basal TSH and T3/T4 levels. Only 3 of 27 (11%) continued to have normal values. Treatment with levo-thyroxine (L-T4) was given to the patients with a high basal TSH level. As 24 of 27 (89%) children had signs of disturbance in the thyroid axis, prophylactic L-T4 treatment for a few years after BMT with TBI may be of value. The main cause of a change in thyroid function after BMT seems to be conditioning with TBI.

Adolescent↗
PubMed1991

Effect of pancreatic phospholipase A2 and gastric lipase on the action of pancreatic carboxyl ester lipase against lipid substrates in vitro.

Preincubation of a triolein/phospholipid/cholesteryl oleate-emulsion in vitro with either pancreatic phospholipase A2 (PLA2) or gastric lipase (GL) resulted in hydrolysis (measured by pH-stat-titration) of cholesteryl [3H]oleate only after human pancreatic carboxyl ester lipase (CEL) was added to the system. No appreciable hydrolysis was observed when CEL was added alone. Consequently, a concerted action either of PLA2 and CEL or of GL and CEL made the substrate cholesteryl oleate available for hydrolysis by CEL. This was the case when cholesteryl oleate was solubilised in a phospholipid-stabilised triglyceride emulsion, which is the physico-chemical form in which the major part of dietary cholesteryl esters are presented to the gastro-intestinal tract of man.

Carboxylesterase↗
PubMed1991

Craniofacial growth in bone marrow transplant recipients treated with growth hormone after total body irradiation.

The effect of growth hormone (GH) treatment on craniofacial development was studied in five children exhibiting growth retardation following bone marrow transplantation. Linear and angular measurements were made on lateral radiographic cephalograms taken prior to the start of GH treatment and after an average treatment time of 1.2 yr. The results showed that the mean growth increments of mandibular length in the GH treated children, exceeded the corresponding values of the control group by 150% during the period of investigation. It is suggested that this dimensional increase in the patients was due to GH stimulation on the chondral growth process in the mandibular condyles.

Adolescent↗
PubMed1991

Hepatic and ileal transport and effect on biliary secretion of norursocholic acid and its conjugates in rats.

The enterohepatic circulation of norursocholic acid (nUC) and its glycine (nUCG) and taurine (nUCT) conjugates was investigated in the rat; cholic acid (C) was studied as control. The biliary recovery of intravenously infused 14C-labeled bile acids was high: nUC, 88%; nUCG, 80%; nUCT, 99%, and C, 90%. Biliary recovery after the same bile acids were infused intraduodenally was similar: nUC, 90%; nUCG, 66%; nUCT, 97%; and C, 99%. The two conjugated bile acids, nUCG and nUCT, were not biotransformed during intestinal or hepatic transport; nUC was also secreted largely unchanged, but approximately 10% was secreted as an unknown conjugate or sulfate; C was completely conjugated with taurine or glycine. To compare the rates of active ileal transport, biliary recovery was measured after an in situ ileal perfusion technique. The rate of absorption of nUC, nUCG, and nUCT was one-fourth to one-half that of cholyltaurine, which served as control. Competition experiments indicated that the same transport system was involved. When infused intravenously, nUC, nUCG, and nUCT induced far less biliary lipid secretion than an identical dose of C; the secretion of both phospholipid and cholesterol was decreased, cholesterol to a greater extent than phospholipid. It is concluded that nUC and its conjugates are well transported by the ileum, are efficiently secreted into bile without undergoing appreciable hepatic biotransformation, and induce bile flow as other hydrophilic bile acids, but in contrast to C induce little phospholipid and cholesterol secretion into bile.

Animals↗
PubMed1991

Bacterial deconjugation and enterohepatic circulation of norursocholic acid conjugates in rats.

Experiments were performed to define the metabolism of norusocholic acid (nUC) conjugates and to quantify to what extent the bile acid pool can be enriched in these bile acids. In vitro incubations of norusocholylglycine (nUCG) and -taurine (nUCT) with small intestinal or cecal content showed deconjugation with only cecal content. Cholylglycine (CG) was deconjugated by small intestinal and cecal content. Infusion of nUCG and CG showed that only a small proportion of nUCG was deconjugated after 24 h of enterohepatic circulation, whereas all CG was deconjugated. When nUCT was administered orally, deconjugation was shown to take place mainly in the cecum. Chronic feeding of nUCT enriched the bile acid pool with only 20% nUCT. We conclude that nUC conjugates are deconjugated primarily by bacteria in the cecum and colon, in contrast to CG, which, in addition to cecum and colon, is deconjugated in the distal small intestine. nUCT and its metabolites do not enrich in the circulating bile acid pool mainly for the following reasons: 1) nUC conjugates have a low affinity for the ileal transport system; 2) nUC, even if formed by deconjugation, is not passively absorbed at a sufficient rate; 3) the small amount of norursodeoxycholic acid formed from nUC is glucuronidated in the liver and glucuronide conjugates do not undergo enterohepatic circulation; and 4) nUC conjugates do not suppress bile acid biosynthesis.

Animals↗
PubMed1991

Pancreatic lipolytic enzymes in human duodenal contents. Radioimmunoassay compared with enzyme activity.

The total pancreatic lipolytic capacity was determined in duodenal contents in healthy humans 10-120 min after a liquid test meal, by estimating the amount of pancreatic lipase, colipase, carboxyl ester lipase, and phospholipase A2 by means of radioimmunoassays and enzymatic assays. The molar concentrations of the different proteins were of the same order of magnitude. The relative specific activity (enzyme activity/milligram immunoreactive protein expressed as a percentage of the specific activity of the respective pure protein) amounted to 75-120% for lipase, 45-80% for colipase, 30-70% for carboxyl ester lipase, and 45-120% for phospholipase A2. These varied, and sometimes low values can be explained by the fact that the enzymes are inhibited or partly inactivated in the duodenal contents by surface denaturation, in which cases the products are still immunoreactive. Also, the proforms of colipase and phospholipase A2 may not always be completely activated. Furthermore, the specific activities of the pure enzymes (and thus the relative specific activities) are related to the methods used, which are not specific enough to distinguish completely the three enzymes and the cofactor in duodenal contents.

Adult↗
PubMed1991

cDNA cloning of carboxyl ester lipase from human pancreas reveals a unique proline-rich repeat unit.

We report the isolation and nucleotide sequence of the cDNA for carboxyl ester lipase (CEL) from human pancreas. CEL was purified from human pancreas and microsequence analysis was performed on the amino-terminal and internal peptides. Peptide sequence was used to design oligonucleotide probes for screening a human pancreas cDNA library. Partial length cDNAs for CEL were isolated from the library, and the 5' portion of the cDNA was obtained using the anchored polymerase chain reaction. The deduced amino acid sequence indicates that mature CEL contains 722 amino acids and is synthesized with a 20 amino acid leader peptide. The amino acid sequence is rich in proline (12.2%), with 68% of the proline residues occurring within the final 25% of protein length. This is due to the occurrence of a series of proline-rich tandem repeat units near the carboxyl terminus, and accounts for the previously observed species variation in CEL size and amino acid composition. The primary sequence of CEL shows strong similarity to members of the serine esterase family, including the identical G-E-S-A-G motif at the putative active site. A striking homology also occurs between CEL and acetylcholinesterase and cholinesterase, essential enzymes of the nervous system. Proteins with cholesteryl esterase activity have been detected in extra-pancreatic tissues including liver, intestine, kidney, aorta, macrophage, and in the milk of some species (human, gorilla, cat, dog), but not others (rat, cow). To clarify the structural relationships between these various esterases and CEL, we used the CEL cDNA to study expression in pancreas and liver. CEL mRNA was abundant in pancreas of human and rat, with the human CEL mRNA approximately 300 nucleotides larger than that from rat. CEL mRNA was not detected in human adult or fetal liver, nor in rat liver. These results indicate that CEL is not synthesized in significant amounts in liver, and suggest that the cholesterol esterase activity that has been described in liver may be due to a distinct enzyme, or may be derived from pancreas, as has been proposed for the cholesterol esterase activity in intestine.

Amino Acid Sequence↗
PubMed1990

Intestinal absorption of retinol and retinyl palmitate in the rat. Effects of tetrahydrolipstatin.

The aim of the present study was to characterize the intestinal absorption of retinol and retinyl palmitate in thoracic duct and bile duct fistulated rats and to investigate the effect of a simultaneously administered lipase inhibitor, tetrahydrolipstatin (THL). Absorption was determined as lymphatic recovery over a 24-hr period, including an initial 12-hr continuous intraduodenal infusion of either [11,12-3H]retinol or [11,12-3H]retinyl palmitate given in emulsified glyceryl trioleate or in mixed micellar solution of monoolein and oleic acid. From micellar dispersion, labeled retinol and retinyl palmitate were recovered in the lymph to 50-60% and both to the same extent. Administered in emulsified form, labeled retinol from fed retinyl palmitate was recovered to 47%, but retinol from fed retinol to only 18%. THL (10(-4) M) in the infusate had no significant effect on the recovery of 14C-labeled oleic acid. The recovery of label from emulsified glyceryl tri[1-14C]oleate was significantly decreased at this concentration of THL (76.5% vs 19.6% recovery). When administered in emulsified form, retinol absorption was not significantly affected by THL at 10(-4) M, while retinyl palmitate absorption was very significantly decreased (5.0% compared to 47.8%). In the presence of THL, retinol absorption from retinyl palmitate in micellar solution was decreased (from 58% to 17%). Most of the retinol in the lymph extracts (72.2 to 91.3) was present as retinyl ester, regardless of the chemical and physical form of administration. Furthermore, THL did not induce any change in this pattern.

Animals↗
PubMed1989

Effects of tetrahydrolipstatin, a lipase inhibitor, on absorption of fat from the intestine of the rat.

Tetrahydrolipstatin (THL) derived by hydrogenation from lipstatin, a lipase inhibitor produced by Streptomyces toxytricini, has been shown to inhibit in vitro the activity of all three lipases secreted to the gastro-intestinal tract; gastric lipase, pancreatic lipase and carboxylester lipase (cholesterol ester hydrolase). The effects of THL on intestinal absorption of fat (transport to the thoracic duct chyle) has now been investigated after intraduodenal infusion in a rat model. Absorption of label from oleic acid when administered with monoolein in micellar bile salt solution was not affected by THL in concentrations up to 10(-4) M calculated on the volume of the aqueous phase. Absorption of free cholesterol in micellar bile salt solution of the lipolytic products of triolein; oleic acid and monoolein, is not significantly affected at a concentration of THL of 10(-4) M. Absorption of cholesterol from cholesteryl oleate under the same conditions is almost completely inhibited. The results indicate that absorption of free cholesterol is not dependent on the activity of pancreatic cholesterol ester hydrolase. The absorption of emulsified triolein was not significantly affected by 10(-5) M THL but decreased to around 30% of the controls by a concentration 10-times higher. There was no significant decrease of cholesterol absorption when administered in emulsified triolein while absorption of cholesteryl oleate was reduced at both concentrations of THL and almost completely at 10(-4) M. Radioactivity from [2-14C]THL when administered emulsified in triolein was recovered in urine, bile and thoracic duct lymph to 10-14, 8-13 and 1-3%, respectively, largely independent on dose administered. Label from [1"-14C] THL was recovered in the same amounts in lymph but much less in bile and urine indicating that the amino acid moiety has been split off early in the absorption process.

Animals↗
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↗