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R J Deckelbaum

Publications and source records attributed to R J Deckelbaum.

At least 19 recordsLinked to original sources
PubMed2000

Endogenously expressed apolipoprotein E has different effects on cell lipid metabolism as compared to exogenous apolipoprotein E carried on triglyceride-rich particles.

Apolipoprotein E (apoE) on model triglyceride-rich particles (TGRP) increases triglyceride (TG) utilization and cholesteryl ester (CE) hydrolysis, independent of its effect on enhancing particle uptake. We questioned whether, under physiological concentrations, endogenously expressed apoE has similar effects on cellular lipid metabolism as compared to exogenous apoE. J774 macrophages, which do not express apoE, were engineered to express endogenous apoE by transfection of human apoE3 cDNA expression constructs (E(+)) or control vectors (E(-)) into the cells. To compare the effects of exogenous apoE and endogenous apoE on TGRP uptake, cells were incubated with or without apoE associated with (3)H-cholesteryl ether-labeled TGRP. Exogenous apoE enhanced TGRP uptake in both E(-) and E(+) cells. E(-) cells displayed significantly higher TGRP uptake than E(+) cells. Sodium chlorate, which inhibits cell proteoglycan synthesis, markedly diminished differences in TGRP uptake between E(-) and E(+) cells, suggesting that endogenous apoE-proteoglycan interaction contributes to differences in uptake between the two cell types. Particle uptake by the LDL receptor, by the LDL receptor related protein, or by scavenger receptors were similar between E(-) and E(+) cells indicating that endogenous apoE expression does not have a general effect on endocytic pathways. Exogenous apoE carried on TGRP stimulated TG utilization and CE hydrolysis in both cell types. However, TG utilization and CE hydrolysis were not affected by endogenous apoE expression. In conclusion, macrophage expression of apoE has very different effects on TGRP metabolism than exogenously supplied apoE. The fluorescence microscopy results in this study showing that exogenous apoE and endogenous apoE were confined in separate cellular compartments support the hypothesis that these differences resulted from distinct intracellular trafficking pathways followed by exogenous apoE bound to TGRP as compared to endogenous cell-expressed apoE.

Apolipoproteins E↗
PubMed2000

Giardia lamblia carriage in Israeli Bedouin infants: risk factors and consequences.

Giardiasis is a common protozoan infection, with varying clinical manifestations. We investigated the associations between Giardia lamblia carriage and environmental, family, illness, and growth characteristics. Bedouin infants (n=234) were followed from birth to age 18-23 months. At monthly home visits, stool samples were obtained, history of illness was determined, and an environmental assessment was done. The comparisons presented are between 4 groups defined by length of carriage of G. lamblia. Study children had a mean+/-SD of 4.1+/-2.9 diarrhea episodes. No illness, environmental, or family characteristics were associated with length of carriage. Significant differences were found in weight-for-age and weight-for-height z scores between the never-positive-for-G. lamblia group and all other carriage groups combined. Faltering growth was shown to be subsequent to G. lamblia infection rather than preceding it. Our findings confirm that G. lamblia carriage is not associated with diarrhea. However, the effect on growth deserves further investigation.

Adolescent↗
PubMed2000

The heparin-binding proteins apolipoprotein E and lipoprotein lipase enhance cellular proteoglycan production.

Apolipoprotein E (apoE) and lipoprotein lipase (LPL), key proteins in the regulation of lipoprotein metabolism, bind with high affinity to heparin and cell-surface heparan sulfate proteoglycan (HSPG). In the present study, we tested whether the expression of apoE or LPL would modulate proteoglycan (PG) metabolism in cells. Two apoE-expressing cells, macrophages and fibroblasts, and LPL-expressing Chinese hamster ovary (CHO) cells were used to study the effect of apoE and LPL on PG production. Cellular PGs were metabolically labeled with (35)[S]sulfate for 20 hours, and medium, pericellular PGs, and intracellular PGs were assessed. In all transfected cells, PG levels in the 3 pools increased 1.6- to 3-fold when compared with control cells. Initial PG production was assessed from the time of addition of radiolabeled sulfate; at 1 hour, there was no difference in PG synthesis by apoE-expressing cells when compared with control cells. After 1 hour, apoE-expressing cells had significantly greater production of PGs. Total production assessed with [(3)H]glucosamine was also increased. This was due to an increase in the length of the glycosaminoglycan chains. To assess whether the increase in PGs was due to a decrease in PG degradation, a pulse-chase experiment was performed. Loss of sulfate-labeled pericellular PGs was similar in apoE and control cells, but more labeled PGs appeared in the medium of the apoE-expressing cells. Addition of exogenous apoE and anti-human apoE antibody to both non-apoE-expressing and apoE-expressing cells did not alter PG production. Moreover, LPL addition did not alter cell-surface PG metabolism. These results show that enhanced gene expression of apoE and LPL increases cellular PG production. We postulate that such changes in vascular PGs can affect the atherogenic potential of arteries.

Animals↗
PubMed1999

Omega-6 polyunsaturated fatty acid-stimulated cellular internalization of phosphorothioate oligodeoxynucleotides: evidence for protein kinase C-zeta dependency.

The rate of cellular internalization of phosphorothioate oligodeoxynucleotides is determined predominantly by adsorptive plus fluid-phase endocytosis. Internalization of a 5'-fluoresceinated phosphorothioate 15mer homopolymer of thymidine (FSdT15) in K562 cells in medium containing lipid-depleted albumin was reduced consistently versus nondepleted albumin. Treatment of K562 and several other cell lines with omega-6 polyunsaturated fatty acids (omega-6 PUFAs; e.g. arachidonic and linoleic acids) but not saturated fatty acids dramatically increased FSdT15 internalization in a concentration-dependent manner and over a wide albumin concentration range. The rate of efflux of FSdT15 from K562 cells was not affected by the omega-6 PUFA, implying that an increase of cellular fluorescence was due to an increase in the in-rate. These data were consistent with the observation that the binding of FSdT15 to the cell surface was also increased in the presence of omega-6 PUFAs. Omega-6 PUFAs are stimulators of protein kinase C (PKC) activity. Inhibition of PKC activity in K562 cells by Go6976, an inhibitor of the classical PKC isoforms, did not block the linoleic acid-induced stimulation of FSdT15 internalization. On the other hand, treatment of cells with Ro318220, which has considerably less isoform specificity, almost totally blocked the effect of linoleic acid on FSdT15 internalization, implying the involvement of a nonclassical PKC isoform in the process. Finally, since the only PKC isoform expressed in K562 cells that also is activated by omega-PUFAs is PKC-zeta, we obtained NIH 3T3 cells expressing a doxycycline-repressible dominant negative PKC-zeta mutant. Expression of the mutant blocked the stimulation of FSdT15 internalization by linoleic acid. Stimulated internalization also was blocked by wortmannin and LY 294002, which are relatively specific inhibitors of phosphatidylinositol 3-kinase (PI 3-K). Taken together, our data suggest that omega-6 PUFA stimulation of fluoresceinated phosphorothioate oligomers may be PKC-zeta dependent, and perhaps PI-3K dependent as well.

Ceramides↗
PubMed1999

Family history of early cardiovascular disease in children with moderate to severe hypercholesterolemia: relationship to lipoprotein (a) and low-density lipoprotein cholesterol levels.

Lipoprotein (a) (Lp(a)) is an established cardiovascular risk factor in adults. We sought to evaluate whether raised Lp(a) levels were predictive of a family history of early cardiovascular disease (CVD) in children already at increased risk for premature atherosclerosis because of elevated low-density lipoprotein (LDL) cholesterol levels. Lp(a) and serum lipid levels were measured in 69 children and offspring with established moderate to severe hypercholesterolemia (serum cholesterol > 170 mg/dL) who were aged 10.7 +/- 4.3 years (range 1.5 to 21 years) and had been referred to a pediatric lipid center. The children represented families with a positive (n = 27) or negative (n = 42) history for premature CVD (<55 years of age in parent or grandparent). In all children, Lp(a) levels ranged from 1 to 140 mg/dL, with a median of 29 mg/dL. Mean total cholesterol, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol levels were 234 mg/dL, 166 mg/dL, and 45 mg/dL, respectively. There was no difference in median Lp(a) levels between the children with a positive family history and those with a negative family history (29.9 mg/dL vs 29.0 mg/dL, respectively). In contrast, children with a positive family history showed significantly higher LDL cholesterol levels (186 +/- 61 mg/dL vs 153 +/- 52 mg/dL, P = .02). Thus, in this group of hypercholesterolemic children, LDL cholesterol but not Lp(a) levels were associated with a family history of premature CVD. Further studies are needed to identify additional specific risk factors associated with the development of CVD in this population.

Adolescent↗
PubMed1999

An independent, inverse association of high-density-lipoprotein-cholesterol concentration with nonadipose body mass.

BACKGROUND: Increasing body mass index (BMI) is associated with progressively lower serum HDL-cholesterol concentrations, although the underlying body-composition compartment accounting for this unfavorable lipid change remains uncertain. OBJECTIVE: Because growing evidence favors a role of lean tissue in HDL homeostasis, the hypothesis was tested that non-adipose tissue components of body mass explain the inverse association of HDL cholesterol and BMI. DESIGN: Fasting serum lipid concentrations and body composition [total, subcutaneous, and visceral adipose tissue; adipose tissue-free mass (ATFM); and skeletal muscle by whole-body magnetic resonance imaging and body cell mass by 40K counting) were evaluated in healthy adults. Body-composition compartments were expressed as height2-normalized indexes. RESULTS: An inverse correlation was observed between serum HDL cholesterol and BMI in women (n = 68; R2 = 0.08, P = 0.023) and men (n = 61; R2 = 0.07, P = 0.046). Significant inverse correlations (P = 0.005-0.02) were also observed between HDL cholesterol and nonadipose components (ie, ATFM, skeletal muscle, and body cell mass) but not between HDL cholesterol and any adipose tissue component. The association between HDL cholesterol and ATFM remained significant after serum triacylglycerol was controlled for. When BMI was entered into the HDL cholesterol-ATFM regression model, BMI was not a significant independent variable. The strongest correlate of serum triacylglycerol was visceral adipose tissue (P = 0.002 for both women and men). CONCLUSIONS: Lean tissues and body cell mass appear to account in part for the long-observed inverse association of HDL cholesterol and BMI. These observations suggest a link between nonadipose tissue compartments and the greater cardiovascular risk associated with high BMI.

Adipose Tissue↗
PubMed1999

Fatty acids: links between genes involved in fatty acid and cholesterol metabolism.

Fatty acids are a major constituent of dietary fats and form an integral part of the cellular membrane and lipoproteins. The gene regulatory potential of fatty acids has long been recognized, but the precise regulatory mechanisms are unknown. The regulatory ability of fatty acids on the expression of a number of genes together with potential mechanisms and pathways of regulation are reviewed. In this review, we emphasize a key aspect of regulation mediated by the sterol regulatory element binding-protein, and its effects on sterol regulatory elements.

Animals↗
PubMed1999

Lipoprotein lipase expression level influences tissue clearance of chylomicron retinyl ester.

Approximately 25% of postprandial retinoid is cleared from the circulation by extrahepatic tissues. Little is known about physiologic factors important to this uptake. We hypothesized that lipoprotein lipase (LpL) contributes to extrahepatic clearance of chylomicron vitamin A. To investigate this, [3H]retinyl ester-containing rat mesenteric chylomicrons were injected intravenously into induced mutant mice and nutritionally manipulated rats. The tissue sites of uptake of 3H label by wild type mice and LpL-null mice overexpressing human LpL in muscle indicate that LpL expression does influence accumulation of chylomicron retinoid. Skeletal muscle from mice overexpressing human LpL accumulated 1.7- to 2.4-fold more 3H label than wild type. Moreover, heart tissue from mice overexpresssing human LpL, but lacking mouse LpL, accumulated less than half of the 3H-label taken up by wild type heart. Fasting and heparin injection, two factors that increase LpL activity in skeletal muscle, increased uptake of chylomicron [3H] retinoid by rat skeletal muscle. Using [3H]retinyl palmitate and its non-hydrolyzable analog retinyl [14C]hexadecyl ether incorporated into Intralipid emulsions, the importance of retinyl ester hydrolysis in this process was assessed. We observed that 3H label was taken up to a greater extent than 14C label by rat skeletal muscle, suggesting that retinoid uptake requires hydrolysis. In summary, for each of our experiments, the level of lipoprotein lipase expression in skeletal muscle, heart, and/or adipose tissue influenced the amount of [3H]retinoid taken up from chylomicrons and/or their remnants.

Animals↗
PubMed1998

Polyunsaturated fatty acids decrease expression of promoters with sterol regulatory elements by decreasing levels of mature sterol regulatory element-binding protein.

Membrane physiology, plasma lipid levels, and intracellular sterol homeostasis are regulated by both fatty acids and cholesterol. Sterols regulate gene expression of key enzymes of cholesterol and fatty acid metabolism through proteolysis of the sterol regulatory element-binding protein (SREBP), which binds to sterol regulatory elements (SRE) contained in promoters of these genes. We investigated the effect of fatty acids on SRE-dependent gene expression and SREBP. Consistent results were obtained in three different cell lines (HepG2, Chinese hamster ovary, and CV-1) transfected with SRE-containing promoters linked to the luciferase expression vector. We show that micromolar concentrations of oleate and other polyunsaturated fatty acids (C18:2-C22:6) dose-dependently (0.075-0.6 mmol) decreased transcription of SRE-regulated genes by 20-75%. Few or no effects were seen with saturated free fatty acids. Fatty acid effects on SRE-dependent gene expression were independent and additive to those of exogenous sterols. Oleate decreased levels of the mature sterol regulatory element-binding proteins SREBP-1 and -2 and HMG-CoA synthase mRNA. Oleate had no effect in sterol regulation defective Chinese hamster ovary cells or in cells transfected with mutant SRE-containing promoters. We hypothesize that unsaturated fatty acids increase intracellular regulatory pools of cholesterol and thus affect mature SREBP levels and expression of SRE-dependent genes.

Animals↗
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↗