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Biomedical subjects

E Granot

Publications and source records attributed to E Granot.

At least 73 records · Page 4Linked to original sources
PubMed1990

ApoE-3-specific metabolism of human plasma very low density lipoproteins in cultured J-774 macrophages.

The effect of apoprotein E on the cellular metabolism of very low density lipoproteins (VLDL) was studied using the J-774 macrophage-like cell line as a foam cell model. Exogenous (plasmatic and recombinant) apoE-3 caused a marked enhancement of the cellular binding, association, and degradation of VLDL fractions I, II, and III from both normolipidemic and hypertriglyceridemic subjects. ApoE-3 did not affect the cellular metabolism of low density lipoproteins (LDL). The stimulatory effect of apoE-3 was specific and was not observed with E-2. ApoE-mediated enhancement of VLDL metabolism was markedly suppressed by competition with LDL or by down-regulation of the LDL receptor while the basal cellular metabolism of VLDL was not. The macrophage, however, appears also to exhibit a second apoE-3-dependent pathway for VLDL metabolism which is discerned from the LDL and scavenger receptors and is relatively resistant to cholesterol in the culture medium. This pathway is responsible for the basal and perhaps a small fraction of the apoE-3-stimulated metabolism of VLDL in the macrophage. Such activity may play a role in promoting foam cell formation by triglyceride-rich lipoproteins.

Apolipoprotein E3↗
PubMed1988

Neutral lipid transfer protein does not regulate alpha-tocopherol transfer between human plasma lipoproteins.

Vitamin E has no known plasma carrier protein and is transported by plasma lipoproteins. The site of association of vitamin E in the lipoprotein particle and the mode of transfer of vitamin E between plasma lipoproteins have not been ascertained. Since neutral lipids (triglycerides and cholesterol esters) exchange between plasma lipoproteins by processes mediated by neutral lipid transfer protein, we questioned that if vitamin E, a hydrophobic molecule, is carried in the core of the lipoprotein particle then its transfer between plasma lipoproteins may be mediated by neutral lipid transfer protein. Transfer of D-alpha(5-methyl-3H)tocopherol from in vitro-labeled human plasma lipoprotein fractions to other plasma lipoproteins was measured under incubation conditions that were designed to yield markedly differing degrees of neutral lipid exchange. Despite the presence of the d greater than 1.21 g/ml lipoprotein-poor plasma fraction or purified lipid transfer protein that resulted in up to a 10-fold increase in neutral lipid transfer, vitamin E transfer between very low density lipoproteins, low density and high density lipoproteins remained constant. Even excess amounts of lipid transfer protein, which caused triglyceride transfer between very low density and high density lipoproteins to reach saturation, failed to affect significantly vitamin E transfer. Vitamin E distribution between lipoprotein fractions did correlated with lipoprotein mass ratios. Vitamin E transfer was higher as the protein ratio of acceptor lipoproteins to donor lipoproteins increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier Proteins↗
PubMed1987

Human plasma cholesteryl ester transfer protein enhances the transfer of cholesteryl ester from high density lipoproteins into cultured HepG2 cells.

The role of human plasma cholesteryl ester transfer protein (CETP) in the cellular uptake of high density lipoprotein (HDL) cholesteryl ester (CE) was studied in a liver tumor cell line (HepG2). When HepG2 cells were incubated with [3H]cholesteryl ester-labeled HDL3 in the presence of increasing concentrations of CETP there was a progressive increase in cell-associated radioactivity to levels that were 2.8 times control. The CETP-dependent uptake of HDL-CE was found to be saturated by increasing concentrations of both CETP and HDL. The CETP-dependent uptake of CE radioactivity increased continuously during an 18-h incubation. In contrast to the effect on cholesteryl ester, CETP failed to enhance HDL protein cell association or degradation. Enhanced uptake of HDL cholesteryl ester was shown for the d greater than 1.21 g/ml fraction of human plasma, partially purified CETP, and CETP purified to homogeneity, but not for the d greater than 1.21 g/ml fraction of rat plasma which lacks cholesteryl ester transfer activity. HDL cholesteryl ester entering the cell under the influence of CETP was largely degraded to free cholesterol by a process inhibitable by chloroquine. CETP enhanced uptake of HDL [3H]CE in cultured smooth muscle cells and to a lesser extent in fibroblasts but did not significantly influence uptake in endothelial cells or J774 macrophages. These experiments show that, in addition to its known role in enhancing the exchange of CE between lipoproteins, plasma CETP can facilitate the in vitro selective transfer of CE from HDL into certain cells.

Carcinoma, Hepatocellular↗
PubMed1987

Familial intestinal pseudoobstruction dominated by a progressive neurologic disease at a young age.

Chronic neuropathic intestinal pseudoobstruction is a rare entity, characterized by recurrent episodes of bowel obstruction without a mechanical obstructive cause. We report five members of two Jewish-Iranian families in whom chronic neuropathic intestinal pseudoobstruction was associated with an identical and unique progressive severe neuronal disease. It appeared within the first two decades of life. The disease consisted of external ophthalmoplegia, ptosis, and severe sensory and motor peripheral neuropathy. Three patients also had neuronal hearing loss. There was no evidence of central nervous system involvement and all patients were mentally intact. The combined disease was confirmed by radiologic, electrophysiologic, and histologic studies. Specific nutritional deficiencies, toxic elements, and systemic diseases affecting both the gastrointestinal tract and the nervous system were ruled out. It seems that these patients suffer from an autosomal recessive, presently unrecognized variant, of chronic neuropathic intestinal pseudoobstruction. In a patient with severe peripheral neuropathy of unknown etiology associated with symptoms suggestive of intestinal obstruction, the possibility of chronic neuropathic intestinal pseudoobstruction has to be considered.

Adolescent↗
PubMed1987

Accelerated transfer of cholesteryl esters in dyslipidemic plasma. Role of cholesteryl ester transfer protein.

Plasma cholesteryl esters, synthesized in the high density lipoproteins (HDL), may be transferred to other lipoproteins by a cholesteryl ester transfer protein (CETP). We found a twofold increase in mass transfer of cholesteryl ester from HDL to apoB-containing lipoproteins in incubated hypercholesterolemic rabbit plasma compared with control. There was a two- to fourfold increase in the activity of CETP, measured in an isotopic assay in hypercholesterolemic plasma. A CETP-like molecule was isolated in increased amounts from hypercholesterolemic plasma. Incubated plasma from four dysbetalipoproteinemic subjects also showed an increase (threefold) in cholesteryl ester mass transfer, compared with normolipidemic controls. There was a twofold increase in the activity of CETP, assayed in whole or lipoprotein-free plasma. Thus, there is increased transfer of cholesteryl esters from HDL to potentially atherogenic apoB-containing lipoproteins in dyslipidemic rabbit and human plasma. The enhanced transfer results in part from increased activity of CETP, possibly reflecting an increase in CETP mass.

Animals↗
PubMed1987

Fructose-1-phosphate and fructose-1,6-bisphosphate aldolases in the small intestinal mucosa.

Reference values are presented for the activity of fructose-1-phosphate aldolase (F1PA) and fructose-1,6-bisphosphate aldolase (FBPA) in the small intestinal mucosa of 32 nonaffected children, 8 nonaffected adults and 2 children with hereditary fructose intolerance (HFI). The 96% confidence limits for F1PA in children are 1.55 to 43.0 u/g protein, completely distinct from the results of the two affected children (1.3 and less than 0.1 u/g protein). With fructose-1,6-bisphosphate as subtrate, the 96% confidence limits are 10 to 324 u/g protein and the values for the two affected children, 23.7 and 9.3 u/g. Among the nonaffected children two mucosal biopsies with F1PA activities less than 1.55 u/g were found. In one mucosal biopsy among the nonaffected children an FBPA activity less than 10 u/g was recorded. The data are interpreted as indicating that the determination of F1PA activity in intestinal mucosa is a highly sensitive test in detecting individuals with HFI. However, the specifity of the test is not absolute. Diagnosis should be based on both clinical and laboratory considerations. The determination of FBPA activity in the same biopsy specimen does not contribute substantially to the differential diagnosis.

Adult↗
PubMed1986

Conversion of human plasma high density lipoprotein-2 to high density lipoprotein-3. Roles of neutral lipid exchange and triglyceride lipases.

Cholesterol esters accumulating in human plasma high density lipoproteins (HDL) are important in conversion of HDL3 to larger HDL2. We studied whether mechanisms of removal of cholesterol esters from HDL might be important in a reverse direction, i.e. conversion of HDL2 to HDL3. Native HDL2 or HDL3 is incubated with very low density lipoproteins (VLDL) and lipoprotein-poor plasma (d greater than 1.21 g/ml) at 37 degrees C. After incubation, "modified" (M) VLDL, and HDL2 or HDL3 are reisolated by ultracentrifugation. In modified M-HDL2 or M-HDL3, triglyceride becomes the major core lipid as the triglyceride/cholesterol ester weight ratio increases 8-10-fold relative to native HDL. With only small changes in protein/phospholipid ratios in M-HDLs, the large decrease in cholesterol ester/protein ratios suggest net cholesterol ester loss from HDL. Quantitative recovery analyses prove that the cholesterol esters lost from HDL are transferred to M-VLDL, which is now richer in cholesterol ester and poorer in triglyceride. These substantial exchanges of HDL lipids are not associated by significant transfer of HDL apoproteins but are dependent on neutral lipid transfer factors present in human lipoprotein-poor plasma (d greater than 1.21 g/ml). Similar results are obtained when purified core lipid transfer protein replaces d greater than 1.21 g/ml plasma in these incubations. After depletion of cholesterol ester from HDL, most but not all, exchanged triglyceride can be removed by lipolysis with either hepatic or lipoprotein lipase, resulting in a post-lipolysis HDL2 with an increased triglyceride content relative to normal HDL. With successive incubations with VLDL, and core lipid transfer factors, HDL2 loses more than two-thirds of its cholesterol esters. After lipolysis of acquired triglyceride, HDL2 is remodeled, in both composition and flotation parameters, toward HDL3.

Apoproteins↗
PubMed1986

Two-hour lactose breath hydrogen test.

Current requirements for the lactose breath hydrogen test (LBHT) include serial expired air samplings and multiple hydrogen (H2) determinations. One hundred thirty-two consecutive LBHTs were evaluated to determine whether multiple samplings are indeed necessary for detection of lactose malabsorption. Expired air samples were collected at 0, 30, 60, 90, 120, 150, and 180 min following ingestion of lactose. Fifty-five LBHTs were positive for lactose malabsorption. All tests showed abnormally elevated breath H2 concentrations at 120 min. The mean value of the change in parts per million (delta ppm) of H2 at 120 min (51.1 +/- 4.7 SEM) was higher than at any other time point. If only the 120-min samples were examined without subtracting the initial concentrations, four of the 77 negative tests (5.2%) would have been falsely positive. Thus, the values of H2 at 0 and 120 min were sufficient to define lactose malabsorption in all cases. We conclude that just as a single blood sample now suffices for determining xylose malabsorption, so expired air sampling at only 0 and 120 min during the LBHT is a reliable method for detecting lactose malabsorption and diminishes the need for acquiring and analyzing multiple samples.

Adolescent↗
PubMed1986

Mechanisms of enhanced cholesteryl ester transfer from high density lipoproteins to apolipoprotein B-containing lipoproteins during alimentary lipemia.

In vitro lipoprotein lipase enhances the cholesteryl ester transfer protein (CETP)-mediated transfer of cholesteryl esters from high density lipoproteins (HDL) to very low density lipoproteins as a result of lipolysis-induced alterations in lipoprotein lipids that lead to increased binding of CETP. To determine if there are similar changes during alimentary lipemia, we measured the transfer of cholesteryl esters from HDL to apo B-containing lipoproteins in incubated fasting and postprandial plasma. In seven normolipidemic subjects there was 2-3-fold stimulation of cholesteryl ester transfer in alimentary lipemic plasma. Cholesteryl ester transfer was stimulated when either the d less than 1.063-or d greater than 1.063-g/ml fraction of lipemic plasma was recombined with its complementary fraction of fasting plasma. To determine the distribution of CETP, plasma was fractionated by agarose chromatography and CETP activity was measured in column fractions in a standardized assay. In fasting plasma, most of the CETP was in smaller HDL, and a variable fraction was nonlipoprotein bound. During lipemia there was increased binding of CETP to larger phospholipid-enriched HDL and in two subjects an increase in CETP in apo B-containing lipoproteins. The total CETP activity of fractions of lipemic plasma was increased 1.1-1.7-fold compared with fasting plasma. Lipemic CETP activity was also increased when measured in lipoprotein-free fractions after dissociation of CETP from the lipoproteins. When purified CETP was incubated with phospholipid-enriched HDL isolated from alimentary lipemic or phospholipid vesicle-treated plasma, there was increased binding of CETP to the phospholipid-enriched HDL compared with fasting HDL, with a parallel stimulation in CETP activity. Thus, the pronounced stimulation of cholesteryl ester transfer during alimentary lipemia is due to (a) an increased mass of triglyceride-rich acceptor lipoproteins, (b) a redistribution of CETP, especially increased binding to larger phospholipid-enriched HDL, and (c) an increase in total activity of CETP, perhaps due to an increased CETP mass.

Adult↗