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Biomedical subjects

R J Deckelbaum

Publications and source records attributed to R J Deckelbaum.

At least 55 records · Page 3Linked to original sources
PubMed1998

Persistent diarrhea in a cohort of Israeli Bedouin infants: role of enteric pathogens and family and environmental factors.

This study examined the role of enteric pathogens and infant, family, and household characteristics in persistent diarrhea. Bedouin infants from southern Israel were followed from birth to age 18-23 months. During monthly home visits, stool samples were obtained, and feeding practices and history of diarrhea were determined, and at age 3 months, an environmental assessment was done. Diarrhea surveillance was either via a network covering all community health care facilities or via weekly interviews with the mother. None of the enteric pathogens examined, including Cryptosporidium parvum and enteroaggregative Escherichia coli, were associated with persistent diarrhea. In multivariate analyses, age at first diarrheal illness and maternal age and maternal education were independently and significantly associated with the risk of persistent diarrhea. These data suggest that persistent diarrhea is a clinical entity that may be related less to a specific enteric pathogen and more to the health experiences of children and their home environment.

Animals↗
PubMed1998

Greater dietary intake of simple carbohydrate is associated with lower concentrations of high-density-lipoprotein cholesterol in hypercholesterolemic children.

Hypercholesterolemic children are increasingly being treated with lipid-lowering diets, but little research has focused on the effects of specific dietary substitutions on HDL cholesterol. We examined the relation between carbohydrate intake and HDL cholesterol in hypercholesterolemic children consuming fat-restricted diets. We obtained 3-d food records for 67 children (mean age: 5.8 +/- 2.5 y) referred for the treatment of hypercholesterolemia. Mean plasma HDL cholesterol was 1.12 +/- 0.21 mmol/L and total cholesterol was 5.99 +/- 1.39 mmol/L. Dietary intake comprised (percentage of total energy) 24.9 +/- 5.1% fat, 59.9 +/- 6.5% carbohydrate, and 16.5 +/- 3.4% protein. Carbohydrate intake included 30.7 +/- 7.4% from simple and 22.6 +/- 6.2% from complex carbohydrates. HDL cholesterol was positively correlated with intake of total fat (r = 0.44, P < 0.001) and saturated fatty acids (r = 0.43, P < 0.001) and inversely correlated with intake of total carbohydrate (r = -0.55, P < 0.001) and simple carbohydrate (r = -0.40, P < 0.001), but not with complex carbohydrate (r = -0.02). The significant inverse relation between simple carbohydrate intake and HDL cholesterol remained after intakes of saturated, monounsaturated, and polyunsaturated fatty acids; intake of complex carbohydrates; dietary cholesterol; plasma triacylglycerol; and age were adjusted for with multivariate techniques. In summary, higher dietary intake of simple carbohydrates was associated with lower HDL-cholesterol concentrations in hypercholesterolemic children consuming reduced-fat diets.

Body Mass Index↗
PubMed1998

Immunologic response to infection with Giardia lamblia in children: effect of different clinical settings.

Infection with Giardia lamblia varies in both its severity and duration. A high incidence of giardiasis in immunoglobulin-deficient individuals suggests a role for the humoral immune response in resistance to Giardia infection. Levels of specific anti-Giardia antibodies were determined in three populations of children infected with the parasite: in children attending a day-care centre in which strict hygiene measures were practised and in whom all Giardia infections were asymptomatic; in a rural population residing under poor hygienic conditions in close proximity to farm animals in which children with Giardia-associated diarrhoeal episodes were studied; and in Bedouin infants followed from birth and in whom a previous study has shown that Giardia infection is almost universal by the age of 2 years. In day-care children, infection was accompanied by a significant increase in anti-Giardia IgM levels, compatible with an initial exposure to the parasite. In populations in which exposure to the parasite occurs at an early age and the prevalence of infestation is high, the pattern of specific antibodies to the parasite is rather uniform and cannot differentiate between current infection and previous exposure. Thus, other immune parameters such as salivary or urinary secretory IgA, which reflect the intestinal IgA response, should be studied in order to delineate further the humoral immune response to Giardia.

Animals↗
PubMed1998

Prevalence of intestinal infections caused by diarrheagenic Escherichia coli in Bedouin infants and young children in Southern Israel.

OBJECTIVE: To evaluate the prevalence of different Escherichia coli categories in symptomatic and asymptomatic infants and children residing in a Bedouin township in Southern Israel. METHODS: A total of 1613 stool samples were collected from a cohort of 234 infants and young children followed from birth up to 2 years of age. E. coli colonies from stool cultures from children during a diarrhea episode and those from nondiarrhea stools were hybridized with DNA probes specific for enteropathogenic, enteroinvasive, enterotoxigenic (ETEC), enteroaggregative, diffuse adherent and enterohemorrhagic strains. RESULTS: There were 1469 of 1613 (91%) samples positive for E. coli. The prevalence of E. coli categories was: enteroaggregative (25.9%); diffuse adherent (21.8%), ETEC (12.9%); enteropathogenic (7.3%); enterohemorrhagic (0.5%); and enteroinvasive (0.2%). ETEC, expressing the heat-stable enterotoxin (ST), was the only category isolated significantly more often from cases than from controls (P = 0.005). Of the two heat-stable enterotoxins screened in this study, only ETEC-heat stable enterotoxin (STh), the form isolated from human pathogenic ETEC, could be associated with diarrhea, whereas ETEC-STp, produced by ETEC of porcine origin, was not related to diarrhea. ETEC infections peaked during the warm, dry season. Prolonged shedding of E. coli postdiarrhea was not found in this population. CONCLUSION: The present cohort study confirmed that in this semiurban area, highly endemic for diarrheal disease, ETEC is an important cause of diarrhea in children.

Arabs↗
PubMed1998

Lipid metabolism.

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Apolipoproteins E↗
PubMed1998

Small dense low density lipoprotein has increased affinity for LDL receptor-independent cell surface binding sites: a potential mechanism for increased atherogenicity.

Small dense low density lipoprotein (LDL) particles have altered apolipoprotein (apo) B conformation and lowered affinity for the LDL receptor (J. Biol. Chem. 1994. 269: 511-519). Herein, we examine the interaction of small dense LDL with cell LDL receptor-independent binding sites. Compared to normal LDL, at low LDL cell media concentrations (<10 microg/ml), small dense LDL had decreased specific binding to the LDL receptor on normal fibroblasts at 4 degrees C, but a 2-fold increased binding to LDL receptor-independent cell sites. At higher LDL concentration (100 microg/ ml), LDL receptor-independent binding of small dense LDL was 4.5-fold that of normal LDL in normal fibroblasts, but greater (2- to 14- fold) in LDL receptor-negative fibroblasts. In LDL receptor-negative fibroblasts at 37 degrees C, small dense LDL had higher (3-fold) cell association than normal size LDL but no effective LDL degradation. At high LDL concentrations (> or =100 microg/ml), LDL binding to normal or LDL receptor-negative fibroblasts was not affected by several anti-apoB monoclonal antibodies or by cell pretreatment with proteases, chondroitinase, or neuraminidase. In contrast, pretreating normal and receptor-negative fibroblasts with heparinase and heparitinase decreased LDL cell binding by 35% and 50%, respectively. Similarly, preincubation of receptor-negative fibroblasts with sodium chlorate, an inhibitor of proteoglycan sulfation, decreased LDL binding by about 45%. We hypothesize that small dense LDL might be more atherogenic than normal size LDL due to decreased hepatic clearance by the LDL receptor, and enhanced anchoring to LDL receptor-independent binding sites in extrahepatic tissues (e.g., the arterial wall), a process mediated, in part, by cell surface proteoglycans.

Apolipoproteins B↗
PubMed1997

Heparan sulfate proteoglycan-mediated uptake of apolipoprotein E-triglyceride-rich lipoprotein particles: a major pathway at physiological particle concentrations.

We explored potential mechanisms of non-low-density lipoprotein (LDL) receptor-mediated uptake of triglyceride-rich particles (TGRP) in the presence of apolipoprotein E (apo E). Human fibroblasts were incubated with model intermediate-density lipoprotein- (IDL-) sized TGRP (10-1000 microg of neutral lipid/mL) containing apo E. The extent of receptor-mediated uptake of TGRP was assessed with (a) an anti-apo E monoclonal antibody, which blocks receptor interaction; (b) incubation with heparin; (c) normal vs LDL receptor-negative fibroblasts; and (d) receptor-associated protein (RAP) to determine the potential contribution of LDL receptor-related protein (LRP). Cell surface heparan sulfate proteoglycan- (HSPG-) mediated uptake was examined with or without the addition of heparinase and heparitinase to cell incubation mixtures. At low particle concentrations (</=100 microg of neutral lipid/mL), almost all apo E-TGRP uptake was via the LDL receptor. At higher particle concentrations, within the physiologic range (>250 microg of neutral lipid/mL), most (>/=60%) particle uptake and internalization was via HSPG-mediated pathways. This HSPG pathway did not involve classical lipoprotein receptors, such as LRP or the LDL receptor. These data suggest that in peripheral tissues, such as the arterial wall, apo E may act in TGRP as a ligand for uptake not only via the LDL receptor and LRP pathways but also via HSPG pathways that are receptor-independent. Thus, at physiologic particle concentrations apo E-TGRP can be bound and internalized in certain cells by relatively low affinity but high capacity HSPG-mediated pathways.

Antibodies, Monoclonal↗
PubMed1997

Lipoprotein metabolism during and after a 6-h infusion ofMCT/LCT vs LCT emulsion in man.

We studied, in man, the intravascular metabolism of two lipid emulsions differing in their triglyceride (TG) fatty acid pattern. One emulsion was composed exclusively of soy bean long-chain triglycerides (LCT), the other of a mixture containing a (1:1, wt:wt) ratio of medium-chain triglycerides (MCT) and LCT (MCT/LCT). Both emulsions contained 10% TG and 1.2% of the same egg yolk phospholipid emulsifier. Six healthy volunteers received both emulsions, in random order, at a rate of 0.2 g TG/kg.h for 6 h. An interval of 2 weeks separated the tests. Although the MCT/LCT emulsion provided 39% more TG molecules than the pure LCT emulsion, plasma TG increased to similar levels, indicating a faster elimination of MCT/LCT. The rise of plasma non esterified fatty acids was greater with MCT/LCT (P < 0.001). LDL-TG enrichment was higher with MCT/LCT (P < 0.025) while net transfer of TG to HDL was similar with both emulsions. Cholesteryl ester (CE) enrichment in the 'VLDL' fraction (largely composed of emulsion particles) was markedly less during MCT/LCT than LCT infusions (P < 0.01). CE enrichment of the 'VLDL' fraction persisted up to 6 h after cessation of both lipid infusions. In conclusion, TG from MCT/LCT emulsion appear to be eliminated faster than LCT during an in vivo infusion in man. In accordance with our previous in vitro data, MCT/LCT infusion was associated with a higher transfer of TG to LDL and in a reverse manner, with a lesser acquisition of CE by emulsion particles as compared to LCT infusion.

Journal Article↗
PubMed1997

Recent developments in lipid emulsions: relevance to intensive care.

For years, intravenous lipid supply has been considered as a means of providing an efficient fuel to many tissues of the body and of preventing or correcting essential fatty acid deficiency. The potential for lipid emulsions to modulate cell function via their content of specific fatty acids and of liposoluble vitamins has not received much attention yet. Soybean [long-chain triglycerides (LCT)] emulsions provide a valuable source of energy, but they are excessively rich in omega-6 essential fatty acids (FAs). Their infusion is associated with an accumulation of linoleate and a reduction of long-chain (> or = C20) omega-6 and omega-3 fatty acids in cell membrane phospholipids, as well as with a depletion of antioxidant status, associated with a reduction of alpha-tocopherol in plasma lipoproteins. Infusions of the mixed medium-chain triglycerides (MCT)/LCT (50%:50%; wt:wt) largely bypass these disadvantages. In addition, plasma elimination of MCT/LCT is faster than that of LCT. Recent advances indicate a great potential for omega-3 FAs incorporated into membrane phospholipids to modulate cell response to various stimuli and to influence several intracellular metabolic processes. Furthermore, some of these FA directly influence the production and the action of important mediators, the eicosanoids. In practical terms, an increased intake of omega-3 FAs may reduce inflammatory and thrombotic responses while protecting tissue microperfusion and immune defenses. Such properties may find interesting applications in several types of intensive care unit patients, provided that omega-3 FA incorporation takes place promptly. We recently had the opportunity to study in vitro and in vivo the metabolism of emulsions made of a mixture of MCT, soybean LCT, and fish oil triglycerides. Plasma elimination of such preparations appeared to be very fast, and their infusion was not associated with a prolonged residence of emulsion particles. In addition, uptake of remnants enriched with omega-3 FAs and liposoluble vitamins was fairly fast and occurred in several types of cells, leading to an efficient incorporation of omega-3 FAs in cell membranes within a few hours. The understanding that remnant uptake plays a significant role in the delivery of components included in lipid emulsions opens new areas of investigation and is likely to find several conditions of applications for new types of preparations.

Antioxidants↗
PubMed1997

Natural history of Giardia lamblia and Cryptosporidium infections in a cohort of Israeli Bedouin infants: a study of a population in transition.

The natural history of Giardia lamblia and Cryptosporidium infections were determined in a cohort of 164 Bedouin children, from a population not previously studied, which is in transition from nomadism to a settled life style. Stools were sampled monthly from birth to two years of age and at all diarrhea episodes. The risk of infection with G. lamblia and Cryptosporidium infection by age two was 91.5% and 48.8%, respectively. Cryptosporidium prevalence was 3-4% at all ages, whereas G. lamblia prevalence was > 30% after age one. Giardia lamblia and Cryptosporidium asymptomatic detection rates were high, 28.5% and 1.6%, respectively. Detection of G. lamblia was higher in diarrhea episode samples obtained before six months of age, but after that age and overall, the detection was lower than in nondiarrhea samples (odds ratio [OR] = 0.8, 95% confidence interval [CI] = 0.7-0.9, P < 0.05). Detection rates of C. parvum were higher in episode-related samples in all age groups (OR = 2.8, 95% CI = 1.9-4.2, P < 0.05) and infections in boys were more frequently symptomatic than in girls. While G. lamblia does not appear to be a consistent pathogen in this population where it is hyperendemic, Cryptosporidium has been shown to be an important cause of diarrhea in young children in the community.

Adolescent↗
PubMed1996

Sterol esterification in yeast: a two-gene process.

Unesterified sterol modulates the function of eukaryotic membranes. In human cells, sterol is esterified to a storage form by acyl-coenzyme A (CoA): cholesterol acyl transferase (ACAT). Here, two genes are identified, ARE1 and ARE2, that encode ACAT-related enzymes in yeast. The yeast enzymes are 49 percent identical to each other and exhibit 23 percent identity to human ACAT. Deletion of ARE2 reduced sterol ester levels to approximately 25 percent of normal levels, whereas disruption of ARE1 did not affect sterol ester biosynthesis. Deletion of both genes resulted in a viable cell with undetectable esterified sterol. Measurements of [14C]acetate incorporation into saponified lipids indicated down-regulation of sterol biosynthesis in the are1 are2 mutant cells. With the use of a consensus sequence to the yeast and human genes, an additional number of the ACAT gene family was identified in humans.

Acetates↗
PubMed1996

Evaluation of hypercholesterolemia in childhood.

For many adults, the risk of atherosclerosis can be reduced by intervention and treatment of known risk factors. Direct proof that similar intervention will be effective in children is not available. However, evidence suggests that prevention beginning in childhood will lead to a decrease in incidence of heart disease later in life. The majority of families are eager to take steps to prevent heart disease in their children, especially if there is a family history of early heart disease. It is the role of the pediatrician to identify those children at risk for early heart disease and to initiate advice on reducing risk factors.

Age Factors↗
PubMed1996

Incorporation of medium chain triacylglycerols into phospholipid bilayers: effect of long chain triacylglycerols, cholesterol, and cholesteryl esters.

The ability of water-insoluble molecules such as triacylglycerols to partition from oil phases into phospholipid interfaces may be crucial to their hydrolysis by lipases in the aqueous environment of plasma and cells. This study uses high resolution and magic angle spinning 13C NMR spectros-copy to measure the solubility of the 8-carbon medium chain triacylglycerol, trioctanoin, in the lamellar structure of phospholipids (vesicles and multilayers) in the presence of other neutral lipids that may compete for an interfacial location (long chain triacylglycerol, cholesteryl ester, and cholesterol). In the presence of a saturating concentration of triolein (approximately 3 mole%), the solubility of trioctanoin in egg phosphatidylcholine vesicles decreased from 10 mole% to 7 mole%. The presence of a saturating concentration of trioctanoin (approximately 10 mole%) decreased the interfacial solubility of long chain triolein to approximately 1 mole%. Cholesteryl oleate in phospholipid vesicles slightly diminished the incorporation of trioctanoin into the surface. The presence of cholesterol reduced the interfacial solubility of trioctanoin, but at a high level of cholesterol (30 mole%), trioctanoin had a solubility of 3 mole%. Thus, even in the presence of other competing neutral lipids, medium chain triacylglycerol retains a favorable location and surface concentration for efficient hydrolysis. 13C NMR analysis thus provides an explanation for preferential hydrolysis of medium, compared to long chain triacylglycerol, in a physical blend of medium and long chain triacylglycerol in a single emulsion particle, and in general, a valuable approach to determine substrate availability at phospholipid surfaces.

Caprylates↗
PubMed1995

Oleate and other long chain fatty acids stimulate low density lipoprotein receptor activity by enhancing acyl coenzyme A:cholesterol acyltransferase activity and altering intracellular regulatory cholesterol pools in cultured cells.

Modification of dietary fatty acid composition results in changes in plasma cholesterol levels in man. We examined the effect of in vitro fatty acid supplementation on low density lipoprotein (LDL) receptor activity in cultured cells and questioned whether changes were related to fatty acid-induced alterations in acyl-CoA: cholesterol acyltransferase (ACAT) activity. Preincubation of cultured cells (i.e. human skin fibroblasts, J774 macrophages, and HepG2 cells) with oleic acid (oleic acid:bovine serum albumin molar ratio 2:1) at 37 degrees C for longer than 2 h resulted in a 1.2- to 1.5-fold increase in LDL cell binding at 4 degrees C and LDL cell degradation at 37 degrees C. Scatchard analysis showed that oleic acid increased LDL receptor number but not LDL affinity (Kd). Fatty acid supplementation of J774 macrophages increased both LDL receptor activity and cholesteryl ester accumulation. The ACAT inhibitor, 58-035, eliminated both effects, and increased ACAT activity preceded stimulation of LDL receptor activity by 1-2 h. Supplementation of macrophages with triolein emulsion particles also increased LDL cell binding and degradation, and addition of cholesterol to the emulsions abolished this effect. Among fatty acids tested, oleate (18:1), arachidonate (20:4), and eicosapentanoate (20:5) demonstrated the greatest effects. We hypothesize that certain fatty acids delivered to cells either in free form, or as triglyceride, first increase cellular ACAT activity, which then causes a decrease in an intracellular free cholesterol pool, signaling a need for increased LDL receptor activity. This mechanism may play a role in the effect of certain dietary fatty acids on LDL metabolism in vivo.

Cells, Cultured↗