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Biomedical subjects

R J Deckelbaum

Publications and source records attributed to R J Deckelbaum.

At least 91 records · Page 5Linked to original sources
PubMed1993

Alterations in plasma alpha- and gamma-tocopherol concentrations in response to intravenous infusion of lipid emulsions in humans.

To study the fate of intravenously infused vitamin E, we infused lipid emulsions rich in gamma-tocopherol (Intralipid, Kabi, Stockholm, Sweden), or in both alpha- and gamma-tocopherols (Lipidem, Hausmann Laboratories, St Gallen, Switzerland); in normal human volunteers. Plasma gamma-tocopherol levels increased in four subjects infused with Intralipid 10% (0.3 g triglyceride [TG]/kg/h for 6 hours) from 3 +/- 1 to 25 +/- 2 nmol/mL, but by 24 hours they decreased to 5 +/- 1 nmol/mL. Although eight times more gamma-tocopherol was infused, plasma alpha-tocopherol levels also increased from 26 +/- 7 to 39 +/- 9 nmol/mL at 8 hours and decreased to 24 +/- 5 nmol/mL at 24 hours. Increases of alpha-tocopherol in the very-low-density lipoprotein (VLDL) density range occurred at 6 and 8 hours, while decreases occurred in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) density ranges at 3, 6, 8, and 24 hours. Infusion of both emulsions in random order to six subjects at therapeutic rates (0.1 g/kg/h for 6 hours) resulted in (1) a threefold increase in plasma gamma-tocopherol concentrations at 6 hours, (2) increases in plasma alpha-tocopherol concentrations only with Lipidem (from 14.3 +/- 1.0 nmol/mL at 0 hours to 18.4 +/- 2.7 at 6 hours and 18.9 +/- 1.1 at 24 hours), and (3) no decreases in lipoprotein alpha-tocopherol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Familial hypobetalipoproteinemia--differences in lipoprotein structure and composition.

Familial hypobetalipoproteinemia represents a heterogeneous group of genetic defects in which the concentrations of plasma apolipoprotein B and apo-B-containing lipoproteins VLDL and LDL are abnormally low. To explore potential effects of different genotypes on plasma lipid patterns, the lipoproteins of two families with hypobetalipoproteinemia were compared using zonal ultracentrifugation and chemical analyses. Heterozygotes differed between families not only in level and composition of apo-B-containing lipoproteins but also in HDL subclass distribution. In one family, heterozygotes had very low apo B levels and their major HDL subfraction was HDL2 as in abetalipoproteinemia, whereas in the second family heterozygotes had apo B levels approximately half on normal and the major HDL subfraction was HDL3 with an HDL elution pattern intermediate between that observed in abetalipoproteinemia and normal subjects. Observations on the HDL system in these two families substantiate the role of cholesteryl ester/triglyceride exchange between HDL and lower-density lipoproteins in the remodelling of HDL in plasma.

Adolescent↗
PubMed1993

Peripheral blood lymphocyte subsets in infants with diarrhea with and without Giardia lamblia infection.

The aim of the present study was to define the cellular immune response during gastrointestinal Giardia lamblia infection in young children. The level of lymphocyte subsets was determined in the peripheral blood of infants with G. lamblia-associated diarrhea or acute gastroenteritis and from control infants without diarrhea. The proportion of peripheral blood lymphocytes (PBL) expressing the CD8 marker (suppressor cytotoxic T cells) and the CD57 marker (natural killer cells and subset of CD8+ T cells) was highest in infants with acute gastroenteritis, lower in infants without diarrhea, and lowest among those with G. lamblia-associated diarrhea. The level of CD4+ PBL (helper T cells) did not differ significantly among the three groups of children tested. The level of memory, or helper-inducer, CD4+CD29+ PBL was increased markedly in acute gastroenteritis as compared with their level among the other two groups, whereas naive or virgin CD4+CD45RA+ PBL had the reciprocal distribution among the three groups of infants. In contrast to acute gastroenteritis from other causes, G. lamblia-associated diarrhea did not elicit changes in lymphocyte subsets.

Antibodies, Monoclonal↗
PubMed1992

Triacylglycerol and phospholipid hydrolysis in human plasma lipoproteins: role of lipoprotein and hepatic lipase.

To explore the interactions of triacylglycerol and phospholipid hydrolysis in lipoprotein conversions and remodeling, we compared the activities of lipoprotein and hepatic lipases on human VLDL, IDL, LDL, and HDL2. Triacylglycerol and phospholipid hydrolysis by each enzyme were measured concomitantly in each lipoprotein class by measuring hydrolysis of [14C]triolein and [3H]dipalmitoylphosphatidylcholine incorporated into each lipoprotein by lipid transfer processes. Hepatic lipase was 2-3 times more efficient than lipoprotein lipase at hydrolyzing phospholipid both in absolute terms and in relation to triacylglycerol hydrolysis in all lipoproteins. The relationship between phospholipid hydrolysis and triacylglycerol hydrolysis was generally linear until half of particle triacylglycerol was hydrolyzed. For either enzyme acting on a single lipoprotein fraction, the degree of phosphohydrolysis closely correlated with triacylglycerol hydrolysis and was largely independent of the kinetics of hydrolysis, suggesting that triacylglycerol removed from a lipoprotein core is an important determinant of phospholipid removal via hydrolysis by the lipase. Phospholipid hydrolysis relative to triacylglycerol hydrolysis was most efficient in VLDL followed in descending order by IDL, HDL, and LDL. Even with hepatic lipase, phospholipid hydrolysis could not deplete VLDL and IDL of sufficient phospholipid molecules to account for the loss of surface phospholipid that accompanies triacylglycerol hydrolysis and decreasing core volume as LDL is formed (or for conversion of HDL2 to HDL3). Thus, shedding of whole phospholipid molecules, presumably in liposomal-like particles, must be a major mechanism for losing excess surface lipid as large lipoprotein particles are converted to smaller particles. Also, this shedding phenomenon, like phospholipid hydrolysis, is closely related to the hydrolysis of lipoprotein triacylglycerol.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1992

Modification of erythrocyte membrane lipid composition induced by a single intravenous infusion of phospholipid-triacylglycerol emulsions in man.

The study aimed to investigate whether, during short term infusion of lipid emulsions in man, red blood cell (RBC) membrane lipid composition was altered and RBC-free cholesterol (FC) could serve as a source of FC accumulated in the plasma. 3 normal subjects were infused intravenously with either 10% Intralipid [10% IL; PL:triglyceride (TG) weight ratio of 0.12] at the rates of 0.1, 0.2 and 0.3 g TG.kg(-1).h(-1) (providing PL intakes of 12, 24, 36 mg.kg(-1).h(-1), respectively) or with 30% Intralipid (30% IL; PL:TG ratio of 0.04) at the rate of 0.3 g TG.kg(-1).h(-1) (providing 12 mg PL.kg(-1).h(-1)). Infusion of 10% IL at a slow rate and 30% IL at a high rate caused no change in RBC and plasma FC content. However, 10% IL infusion at intermediate and high rates induced a significant decrease in RBC-FC: PL ratio. This change was still present at 18 h after the cessation of high rate infusion. RBC-FC: PL ratio and plasma PL measured during infusion were significantly correlated (r = -0.87, p < 0.001). FC efflux from RBC appears to contribute to the rise in plasma FC. This study indicates that the excessive amount of PL present as liposomes in some intravenous lipid emulsions can alter erythrocyte membrane lipid composition.

Journal Article↗
PubMed1992

Effects of essential fatty acid contents of lipid emulsions on erythrocyte polyunsaturated fatty acid composition in patients on long-term parenteral nutrition.

The effect of the long-term intravenous infusion of 2 lipid emulsions, differing in essential fatty acid (EFA) content, on fatty acid pattern of red blood cell (RBC) was investigated in 5 patients with inflammatory bowel disease. They were randomly assigned to receive daily intravenous infusion of either a soybean emulsion or a mixed medium-chain triacyl-glycerols (MCT): soybean emulsion, followed by the other, each for a period of 3 months. The soybean emulsion contained exclusively long-chain triacylglycerols (LCT) with 54% of C18:2n-6 and 6% of C18:3n-3. The mixed emulsion consisted of a 50:50 (w:w) mixture of soybean LCT and MCT, providing half the amount of the same EFA compared to LCT emulsion. The same phospholipid emulsifier was used in both preparations. Infusion of LCT for a 3 month period modified RBC fatty acid pattern as follows: 18:2n-6 increased, 20:4n-6 decreased as well as n-6:n-3 ratio. By contrast, infusion of MCT/LCT did not alter RBC fatty acids, and even tended to correct a pattern altered by the previous LCT infusion. The study demonstrates that soybean LCT provides an excess of C18: 2n-6 which affects the balance between RBC fatty acids in adult patients. Decreasing the intake of C18:2n-6 and C18: 3n-3, by using a mixed MCT/LCT emulsion, appears more appropriate for keeping a balanced pattern.

Journal Article↗
PubMed1992

Effect of liposomal content of lipid emulsions on plasma lipid concentrations in low birth weight infants receiving parenteral nutrition.

We studied the effects of phospholipid liposomes present in intravenously administered lipid emulsions on plasma lipid levels in preterm infants given 10% and 20% lipid emulsions. Twenty premature infants (birth weight 1454 +/- 54 gm) on a parenteral nutrition regimen received up to 4 gm triglycerides per kilogram per day in a 20% lipid emulsion for 2 weeks, and then received the 10% emulsion at 2 gm triglycerides per kilogram per day, which delivered the same total phospholipid load but twice the amount of liposomes. Triglyceride, total cholesterol, and phospholipid concentrations increased significantly when the infants were given 2 gm triglycerides per kilogram per day in the 10% emulsion rather than 4 gm/kg per day in the 20% emulsion (44 +/- 4 to 57 +/- 5 mg/dl, 134 +/- 6 to 162 +/- 9 mg/dl, and 204 +/- 8 to 251 +/- 10 mg/dl, respectively). Lipoprotein analysis indicated the presence of lipoprotein X-like particles in the low-density lipoprotein fraction and an increase of the intermediate-density lipoprotein fraction in infants who received the 10% emulsion. The presence of excess phospholipids in the 10% emulsion was associated with greater plasma lipid alterations. Therefore the use of 20% rather than 10% emulsion allows for more efficient triglyceride clearance, even at a higher triglyceride intake. Administration of emulsions that are relatively poor in phospholipid liposomes may allow delivery of > 2 gm triglycerides per kilogram per day to low birth weight infants.

Cholesterol↗
PubMed1992

Investigation of human giardiasis by karyotype analysis.

The patterns of transmission of Giardia lamblia and the potential contribution of strain differences to pathogenicity of infection is poorly understood. We used pulsed field gradient gel electrophoresis (PFGE) to separate chromosome-sized DNA molecules of 22 stocks of G. lamblia isolated from 13 individuals (6 symptomatic, 7 asymptomatic) living in Jerusalem. PGFE gels run under a variety of conditions revealed up to nine ethidium bromide-stained bands per isolate ranging in size from 0.7 to greater than 3 megabasepairs. Relative staining intensities indicated that some bands contained multiple chromosomes. Major differences in the number, size, and intensity of bands allowed a clear differentiation of the karyotypes of isolates from each of the different individuals. This is in contrast to previous studies where the karyotype of different isolates have been strikingly homogeneous. Hybridization of Southern blots with surface antigen, beta-tubulin, and ribosomal RNA genes revealed that these gene families were distributed to different sized chromosomes amongst the different isolates. PFGE thus revealed major differences in the karyotypes of different G. lamblia isolates that were obtained over a short period of time from a relatively confined geographic area. In contrast, karyotypes of isolates established either by direct cultivation of duodenal trophozoites or by excystation of stool cysts from the same individuals were almost identical. Also, isolates from the same individuals obtained over a prolonged period of time revealed only minor differences in their karyotype, suggesting that recurrent infection can be caused by genetically similar organisms. We conclude that chronic giardiasis can result from recurrence of occult infection or reinfection from a common source.

Adolescent↗
PubMed1992

Lipoprotein lipase-mediated uptake and degradation of low density lipoproteins by fibroblasts and macrophages.

Lipoprotein lipase (LPL), the rate limiting enzyme for hydrolysis of lipoprotein triglyceride, also mediates nonenzymatic interactions between lipoproteins and heparan sulfate proteoglycans. To determine whether cell surface LPL increases LDL binding to cells, bovine milk LPL was added to upregulated and nonupregulated human fibroblasts along with media containing LDL. LDL binding to cells was increased 2-10-fold, in a dose-dependent manner, by the addition of 0.5-10 micrograms/ml of LPL. The amount of LDL bound to the cells in the presence of LPL far exceeded the capacity for LDL binding via the LDL receptor. Treatment of fibroblasts with heparinase and heparitinase resulted in a 64% decrease in LPL-mediated LDL binding. Compared to studies performed without LPL, more LDL was internalized and degraded in the presence of LPL, but the time course was slower than that of classical lipoprotein receptor mediated pathways. In LDL receptor negative fibroblasts, LPL increased surface bound LDL > 140-fold, intracellular LDL > 40-fold, and LDL degradation > 6-fold. These effects were almost completely inhibited by heparin and anti-LPL monoclonal antibody. LPL also increased the binding and uptake by fibroblasts of apolipoprotein-free triglyceride emulsions; binding was increased > 8-fold and cellular uptake was increased > 40-fold with LPL. LPL increased LDL binding to THP-1 monocytes, and increased LDL uptake (4.5-fold) and LDL degradation (2.5-fold) by THP-1 macrophages. In the absence of added LPL, heparin and anti-LPL monoclonal antibodies decreased LDL degradation by > 40%, and triglyceride emulsion uptake by > 50%, suggesting that endogenously produced LPL mediated lipid particle uptake and degradation. We conclude that LPL increases lipid and lipoprotein uptake by cells via a pathway not involving the LDL receptor. This pathway may be important for lipid accumulation in LPL synthesizing cells.

Animals↗
PubMed1992

Cryopreservation with sucrose maintains normal physical and biological properties of human plasma low density lipoproteins.

The ability to preserve low density lipoprotein (LDL) preparations frozen for weeks and months without changes in structure or biological properties is of potential use in long-term comparative studies of LDL. We demonstrate that freeze-thawing of LDL causes marked alterations in its structure and biological behavior, and that such changes can be prevented by the addition of sucrose to the LDL solution prior to freezing. Freezing LDL at -70 degrees C in the absence of sucrose resulted in aggregation and fusion of particles as measured by electron microscopy, spectrophotometric absorption, and column gel filtration. This was associated with increased binding affinity of monoclonal antibodies at epitopes distant from the receptor binding region. Functional changes induced by freezing included 3- to 10-fold increases in binding at 4 degrees C and 37 degrees C, and uptake of LDL in fibroblasts, attributable mainly to increases in nonspecific binding processes. Cryopreservation of LDL in 10% sucrose (w/v) completely prevented the structural and functional changes incurred after short-term freezing, and LDL cryopreserved in sucrose for as long as 18 months displayed cell binding, uptake, and degradation very similar to that of freshly obtained LDL.

Cryopreservation↗
PubMed1991

Safety of the American Heart Association Step 1 Diet in childhood.

Can we totally answer the question of the safety of the American Heart Association Step 1 Diet in children over the age of 2 years? Available evidence certainly points to this diet as being safe and not harmful to growing children. A major concern of cholesterol-lowering diets is the misapplication of nutritional guidelines. However, this concern is not exclusive to cardiovascular related nutrition. Therefore, we feel confident that this diet can be implemented in the general population without any adverse effects on growth and development in North American children. It seems prudent to continually monitor children in different settings as is being currently evaluated in certain ongoing studies such as the Dietary Intervention Study in Children (DISC). The DISC program is monitoring children's growth, development, and nutritional status to insure no long-term adverse effects of Step 1 Diets. The focus of future strategies and investigations should be to identify effective methods for the dissemination of accurate nutritional information. Proper education via school programs, the various forms of media, and instructions from educated allied health professionals may all play a major role. It is essential that a variety of strategies be used to provide information and guidance to the general population and to families with children who have high blood cholesterol levels.

Cardiology↗
PubMed1991

Family history fails to identify many children with severe hypercholesterolemia.

Optimal strategies for identifying children with hypercholesterolemia have not been established. Several groups have advocated that testing of serum cholesterol levels be limited to those children who have family histories of hyperlipidemia or premature coronary heart disease. We studied the ability of comprehensive family histories to identify children with hyperlipidemia in a group of 114 children (mean age, 8 +/- 4 years) who were referred for treatment of hypercholesterolemia. A positive family history was defined according to guidelines of the American Academy of Pediatrics. The mean fasting total cholesterol in the children was 5.74 +/- 1.42 mmol/L (222 mg/dL). Family history was negative for hypercholesterolemia or premature coronary heart disease in 22 (22%) of 100 children with total cholesterol levels greater than the 75th percentile for their ages, in 13 (18.3%) of 71 children with total cholesterol levels greater than the 95th percentile for their ages, and in four (11.8%) of 34 children with presumed heterozygous familial hypercholesterolemia. Of the 78 children who had both hypercholesterolemia and positive family histories, hyperlipidemia was reported in 72 families, whereas premature heart disease was reported in only 27. We conclude that in a population of children referred because of known hypercholesterolemia, a detailed family history not only fails to identify many children with mild hypercholesterolemia, but also fails to identify a significant proportion of children with markedly elevated cholesterol levels. Additionally, in families of children with hypercholesterolemia, a history of hyperlipidemia is more common than a history of premature heart disease.

Adolescent↗
PubMed1990

Medium-chain versus long-chain triacylglycerol emulsion hydrolysis by lipoprotein lipase and hepatic lipase: implications for the mechanisms of lipase action.

To explore how enzyme affinities and enzyme activities regulate hydrolysis of water-insoluble substrates, we compared hydrolysis of phospholipid-stabilized emulsions of medium-chain (MCT) versus long-chain triacylglycerols (LCT). Because substrate solubility at the emulsion surface might modulate rates of hydrolysis, the ability of egg yolk phosphatidylcholine to solubilize MCT was examined by NMR spectroscopy. Chemical shift measurements showed that 11 mol % of [13C]carbonyl enriched trioctanoin was incorporated into phospholipid vesicles as a surface component. Similar methods with [13C]triolein showed a maximum solubility in phospholipid bilayers of 3 mol % (Hamilton & Small, 1981). Line widths of trioctanoin surface peaks were half that of LCT, and relaxation times, T1, were also shorter for trioctanoin, showing greater mobility for MCT in phospholipid. In assessing the effects of these differences in solubility on lipolysis, we found that both purified bovine milk lipoprotein lipase and human hepatic lipase hydrolyzed MCT at rates at least 2-fold higher than for LCT. With increasing concentrations of MCT, saturation was not reached, indicating low affinities of lipase for MCT emulsions, but with LCT emulsion incubated with lipoprotein lipase, saturation was reached at relatively low concentration, demonstrating higher affinity of lipase for LCT emulsions. Differences in affinity were also demonstrated in mixed incubations where increasing amounts of LCT emulsion resulted in decreased hydrolysis of MCT emulsions. Increasing MCT emulsion amounts had little or no effect on LCT emulsion hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Fatty acid control of lipoprotein lipase: a link between energy metabolism and lipid transport.

Lipoprotein lipase (LPL) catalyzes the flux-generating step in transport of fatty acids from lipoprotein triacylglycerols into tissues for use in metabolic reactions. In vitro studies have shown that fatty acids can bind to the enzyme and impede its other interactions. In this study we have searched for evidence of fatty acid control of LPL in vivo by rapid infusion of a triacylglycerol emulsion to healthy volunteers. During infusion the activity of LPL but not of hepatic lipase increased in plasma, but to different degrees in different individuals. The time course for the increase in LPL activity differed from that for triacylglycerols but followed the plasma levels of free fatty acids. This was true during infusions and when the emulsion was given as a bolus injection. In particular there were several instances when plasma triacylglycerol levels were very high but free fatty acids and LPL activity remained low. Model studies with bovine LPL showed that fatty acids displace the enzyme from heparin-agarose. We suggest that in situations when fatty acids are generated more rapidly by LPL than they are used by the local tissue, they cause dissociation of the enzyme from its binding to endothelial heparin sulfate and are themselves released into circulation.

Adult↗