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E Levy

Publications and source records attributed to E Levy.

At least 127 records · Page 7Linked to original sources
PubMed1996

The genetic basis of primary disorders of intestinal fat transport.

For decades, research interest has focused on hypertriglyceridemia and hypercholesterolemia, because of their association with atherosclerosis. Recently, however, increasing attention has been paid to rare hypolipidemic states that can cause adverse consequences in young patients. Studies of genetic disorders of fat transport have afforded new insights into the mechanisms involved in intestinal lipid handling and lipoprotein metabolism. This article reviews briefly the current state of knowledge about inherited lipoprotein deficiencies, including abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease. These disorders share many common characteristics: they all cause fat malabsorption, low levels of circulating lipids and fat-soluble vitamins, failure to thrive in early childhood, ataxic neuropathy and visual impairment. However, their etiology is genetically different. Abetalipoproteinemia is caused by the absence of microsomal transfer protein, whereas hypobetalipoproteinemia is due to defects in the apolipoprotein B gene. The etiopathogenesis of chylomicron retention disease is as yet unexplained. Research on these rare, inherited fat disorders of absorption will continue to provide significant advances in our understanding of human physiology and may yield novel therapeutic approaches to atherosclerosis.

Animals↗
PubMed1995

Malondialdehyde-modified HDL leads to accumulation of cholesterol in rat liver endothelial cells.

In order to study in vivo the effect of modified high density lipoprotein (HDL) on the movement of free cholesterol to liver cells and bile, we injected i.v. into rats, native or malondialdehyde modified HDL labelled with [14C]cholesterol. Bile analysis indicated that the contribution of labelled cholesterol to bile acid secretion was diminished in the group receiving MDA-modified HDL when compared to control group. On the other hand, the liver analysis revealed higher radioactivity in the treated group. A separation of liver cells into parenchymal, endothelial, and kupffer at 90 min after the injection of MDA-modified HDL or native HDL indicated that the endothelial cell uptake of labelled free cholesterol from MDA-modified HDL was 2.6-fold higher than for native HDL. It is suggested that liver endothelial cells may be involved in the protection against atherogenoic oxidized lipoprotein. However, with regard to our finding, the uptake of cholesterol from modified HDL was detrimental to bile acid secretion.

Animals↗
PubMed1995

Enalapril treatment of posttransplant erythrocytosis: efficacy independent of circulating erythropoietin levels.

To determine the mechanism of action by which angiotensin-converting enzyme (ACE) inhibitors lower hematocrit in patients with posttransplant erythrocytosis, indices of red blood cell production and red blood cell destruction were obtained serially for 6 months from 10 renal transplant patients receiving treatment with enalapril for this problem. Before treatment, five patients had an elevated red blood cell mass, four had plasma volume contraction, and one had both. The mean hemoglobin concentration decreased by 2 g/dL (range, 0.5 to 3.3 g/dL), from 17 +/- 1 g/dL to 15 +/- 1 g/dL (P = 0.001) following 6 months of enalapril therapy. Similarly, the mean hematocrit decreased by 8% (range, 3% to 12%), from 52% +/- 2% to 44% +/- 3% (P = 0.001) during the same period. The mean reticulocyte count tended to decrease, although the change was not significant. The red blood cell mass decreased dramatically by 15% to 50%, from 32 +/- 9 mL/kl to 23 +/- 4 mL/kg (P = 0.008). Although serial erythropoietin levels declined steadily in two patients, there was no consistent change in the other patients. Mean levels decreased modestly, from 20 +/- 11 mU/mL at baseline to 12 +/- 5 mU/mL at 6 months, a change that was not statistically significant. Mean levels at each time point were not statistically different from the mean pretreatment value. Furthermore, during enalapril therapy, there was no correlation between mean circulating erythropoietin level and mean hematocrit (r = 0.43, P = 0.20) or hemoglobin concentration (r = 0.36, P = 0.30) or between changes in these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The relationships among serum uric acid, plasma insulin, and serum lipoprotein levels in subjects with spinal cord injury.

Relationships were investigated among serum uric acid (UA), the insulin response to a standard oral glucose load (75 g), and serum lipoprotein levels in 197 individuals with chronic spinal cord injury (SCI). All subjects had normal liver and renal function. None had a prior history of diabetes mellitus or gout. The mean age of subjects was 50 +/- 1 years, duration of injury (DOI), 18 +/- 1 years, and body mass index (BMI), 25 +/- 0.4 kg/m2. No significant differences were found between those with paraplegia or quadriplegia for any of the parameters measured. The mean serum UA values were not significantly different among the subgroups of subjects with normal glucose tolerance, impaired glucose tolerance, or diabetes mellitus (5.6 +/- 0.2 mg/dl, 5.6 +/- 0.2 and 5.7 +/- 0.3, respectively). Approximately one-half of the subjects had an abnormality in oral glucose tolerance. The levels of serum UA (p < 0.001) and serum triglycerides (TG) (p < 0.01) in the subgroup with hyperinsulinemia were significantly higher than in the subgroup with normal insulin levels. By linear regression analyses, the serum UA concentration was positively correlated with peak plasma insulin level (r = 0.31, p < 0.001), and BMI (r = 0.20, p < 0.01), but not with age, DOI, or peak glucose. The data suggest that in subjects with chronic SCI, as in the healthy able-bodied population, hyperuricemia is associated with hyperinsulinemia, obesity and abnormal lipoprotein metabolism.

Adult↗
PubMed1995

Caco-2 cells as a model for intestinal lipoprotein synthesis and secretion.

Caco-2 cells, an intestinal cell line derived from a human colorectal carcinoma that spontaneously differentiates under standard culture conditions, lends itself to the in vitro study of human gut in view of its efficient intestinal transport processes. Among its multiple biological functions are those related to the absorption, transport, and metabolism of lipids and lipoproteins. Despite their intestinal origin, confluent Caco-2 cell monolayers primarily express L-FABP for the uptake of apical dietary long chain fatty acids, incorporating them into triglycerides by the glycerol 3-phosphate pathway, and assembling very-low-density lipoprotein, high-density lipoprotein, and low-density lipoprotein. The monoacyl-glycerol pathway is inactive in Caco-2 cells. Furthermore, the secretion of newly synthesized triglyceride-rich lipoproteins is very restricted, despite abundant production of apolipoprotein (apo) B. The regulation of apoB synthesis and its mRNA editing at the enterocyte level has been intensively examined in Caco-2 cells. Luminal fatty acids, calcium ion, as well as vitamins and hormones are known to modulate the apoB-48/apoB-100 at the transcriptional and/or translational level. The regulation of 3-hydroxy-3-methylglutaryl-CoA reductase and acyl-CoA: (cholesterol acyltransferase), the key enzymes governing intracellular cholesterol handling, have also been extensively examined in Caco-2 cells. In many respects this cell line provides an excellent in vitro model for the investigation of intestinal lipoprotein metabolism; however, their limited secretion capacity remains a potential drawback to comparisons with the in vivo physiological state.

Animals↗
PubMed1995

Early onset Alzheimer's disease in a South American pedigree from Argentina.

We report the clinical, SPET, immunohistochemical and DNA features of an early-onset familial Alzheimer's disease (FAD) in an Argentine pedigree of South American indian ethnic background. Pedigree spans 5 generations comprising more than 110 biological relatives. Clinical data supported the diagnosis of early onset FAD (mean age at onset 38.9 years) in 10 family members, including 3 with pathological confirmation (mean age at death 48.5). The pattern of transmission suggested autosomal dominant inheritance. Prominent features were mood changes, early language impairment, myoclonus, seizures and cerebellar signs. SPET displayed bilateral frontal, temporo-parietal and cerebellar hypoperfusion in early stages and in an asymptomatic member at risk, suggesting that SPET may have predictive value in this family. Immunohistochemistry showed beta amyloid deposits within neuritic plaques and vessel walls and no anti-PrP immunoreactivity. DNA analysis showed no abnormalities in the beta amyloid precursor protein gene. The identification of additional genetic defects in well characterized independent FAD pedigrees will contribute to the understanding of the pathogenesis of Alzheimer's disease.

Adult↗
PubMed1995

Tumor necrosis factor-alpha inhibits lipid and lipoprotein transport by Caco-2 cells.

Cytokines, important mediators of inflammation, have been shown to cause disturbances in circulating and hepatic lipid metabolism. Although the intestine plays a major role in dietary fat transport and largely contributes to plasma lipoproteins, the effects of cytokines on intestinal lipid handling remain unknown. In the present study, the modulation of lipid, apoprotein, and lipoprotein synthesis and secretion by tumor necrosis factor-alpha (TNF-alpha) was investigated in Caco-2 cells. Highly differentiated and polarized cells (20 days in culture) were incubated for 20 h with recombinant human TNF-alpha (100-500 ng/ml). No cytotoxic effect of TNF-alpha cells was observed, as indicated by the determinations of Caco-2 cell viability and monolayer transepithelial resistance. Moreover, no differences in cell maturation (sucrase activity) or cell proliferation ([3H]thymidine incorporation and cell cycle analysis) were detected between treated and control cultures. Significant inhibition of lipid secretion by TNF-alpha was observed, with the greatest reduction at 500 ng/ml. TNF-alpha significantly decreased Caco-2 cell secretion of phospholipids (22%), triglycerides (30%), and cholesteryl ester (37%). It also significantly diminished the export of newly synthesized low-density lipoproteins (LDL; 20%) and high-density lipoproteins (HDL; 13%), with a lesser effect on very low-density lipoproteins (VLDL; 3%). The lipid composition of these lipoproteins was minimally affected. De novo synthesis of apo A-I, apo B-100, and apo B-48 was also markedly reduced by TNF-alpha. Sphingomyelinase activity was not increased and cell content of sphingomyelin was not altered, suggesting that inhibitory effects on lipid and apoprotein of TNF-alpha were not mediated by the ceramide pathway. Our results indicate that TNF-alpha may play a role in modulating intestinal lipid metabolism, thus affecting circulating lipoproteins.

Apolipoproteins↗
PubMed1995

Effects of calcitriol on proliferation and differentiation of human fetal jejunum.

Several lines of evidence suggest a role for calcitriol in the regulatory mechanisms of intestinal development. Using organ culture as a model, we have verified whether this hormone influenced the cellular proliferation and differentiation processes of the developing human jejunum. We show that calcitriol supports a proliferative process in the fetal human jejunum at 11 weeks of gestation and a differentiating activity in samples obtained between 16 and 20 weeks. The present data therefore suggest that calcitriol has a biphasic effect on the development of the human intestinal epithelium and warrants caution in extrapolating to human, data observed in developing rodents and human carcinoma cell lines.

Calcitriol↗
PubMed1995

Cystatin C mutation in an elderly man with sporadic amyloid angiopathy and intracerebral hemorrhage.

BACKGROUND: Cerebral amyloid angiopathy (CAA) with intracerebral hemorrhage (ICH) occurs both sporadically and as a result of mutations in either cystatin C or the amyloid precursor protein. ICH due to cystatin C mutations typically occurs in young people of Icelandic origin. CASE DESCRIPTION: We report a case of sporadic CAA with ICH in an elderly Croatian man with a mutation in cystatin C identical to that found in Icelandic hereditary cerebral hemorrhage with amyloidosis. CONCLUSIONS: This is the first case report of sporadic CAA associated with the same mutation causing hereditary cerebral hemorrhage with amyloidosis of the Icelandic type. Sporadic CAA may thus be associated with genetic mutations in some patients. The frequency of these mutations is yet to be determined.

Cerebral Amyloid Angiopathy↗
PubMed1995

Immunocytochemical investigation of insulin secretion by pancreatic beta-cells in control and diabetic Psammomys obesus.

Hyperproinsulinemia is a characteristic feature of non-insulin-dependent diabetes mellitus (NIDDM) caused by pancreatic beta-cell dysfunction through a secretion-related alteration or impaired proinsulin processing. We have investigated the insulin processing and secretion in Psammomys obesus fed with low- and high-energy diets, which represent a model for diet-induced NIDDM. With a high-energy diet the animals develop hyperglycemia and hyperinsulinemia, whereas those maintained on a low-energy diet remain normoglycemic. Although a large amount of insulin immunoreactivity was detected in beta-cells of the normoglycemic compared to hyperglycemic animals, in situ hybridization for insulin mRNA demonstrated a particularly high signal in the beta-cells of the hyperglycemic animals. By electron microscopy, the beta-cells of normoglycemic animals displayed large accumulations of secretory granules, whereas those of the hyperglycemic animals contained very few granules and large deposits of glycogen. These results reflect a secretory resting condition for the cells of the normoglycemic animals in contrast to stimulated synthetic and secretory activities in the cells of the hyperglycemic ones. Using colloidal gold immunocytochemistry at the electron microscopic level, we have examined subcellular proinsulin processing in relation to the convertases PC1 and PC2. Immunolabeling of proinsulin, insulin, C-peptide, PC1, and PC2 in different cell compartments involved in beta-cell secretion were evaluated. Both PC1 and PC2 antigenic sites were detected in beta-cells of hyperglycemic Psammomys, but their labeling intensity was weak compared to the cells of normoglycemic animals. In both groups of animals, higher levels of PC2 were found in the Golgi apparatus than in the immature granules. Major decreases in proinsulin, insulin, PC1, and PC2 immunoreactivity were recorded in beta-cells of the hyperglycemic Psammomys. In addition, all these antigenic sites were detected in lysosome-like structures, revealing a major degradation process. These results suggest that the insulin-secreting cells in hyperglycemic Psammomys obesus are in a chronic secretory state during which impaired processing of proinsulin appears to take place.

Animals↗
PubMed1995

Isolated renal mucormycosis: case report and review.

The 15th reported case of isolated renal mucormycosis (infection of the kidney with fungus of the order Mucorales, in the absence of infection elsewhere in the body) is presented. The patient was a 36-year-old human immunodeficiency virus-infected man, actively using iv drugs, who suffered 6 wk of flank pain and fever before diagnosis was made by percutaneous renal biopsy. He received 4 months of amphotericin B treatment, then no therapy for 6 months before dying with no evidence of mucormycosis. Isolated renal mucormycosis should be suspected in those with an underlying immunocompromising illness or history of iv drug use who have persistent flank pain and fever, but sterile urine cultures. Computed tomographic scanning with contrast should then be performed; findings of severe inflammation or bacterial infection, despite an indolent clinical course with sterile or nondiagnostic urine and blood cultures, are suggestive of isolated renal mucormycosis, and renal biopsy under computed tomographic guidance should be performed, despite the potential risk of disseminated infection. Although our patient was treated with amphotericin B alone, nephrectomy with or without amphotericin B therapy appears to be more likely to cure infection and relieve pain and constitutional symptoms.

AIDS-Related Opportunistic Infections↗
PubMed1995

Essentiality of omega-3 and omega-6 fatty acids for efficient liver sterol metabolism.

Abundant data from both experimental animals and humans now support the conclusion that the incidence of atherosclerosis is related to the concentration of plasma cholesterol. Cholesterol homeostasis in the body is maintained by regulatory mechanisms, which control the input and output processes. The liver plays a key role in cholesterol balance. In this organ, the major part of the cholesterol synthesis, cholesterol conversion to bile acids and the delivery of cholesterol to the plasma in the form of lipoprotein remnants, low and high density lipoproteins. While many studies have related dietary intake of fatty acids to concentrations of cholesterol in the circulation, their potential effects on liver sterol metabolism have received relatively less attention. However, the liver represents the target of many stimuli capable of affecting cholesterol homeostasis. This review will focus on the regulation of liver sterol metabolism by omega-3 versus omega-6 fatty acids.

Animals↗
PubMed1995

Familial hypercholesterolemia: molecular, biochemical, and clinical characterization of a French-Canadian pediatric population.

BACKGROUND: Familial hypercholesterolemia (FH) is a dominantly-inherited disorder attributable to a defect in the low-density lipoprotein (LDL) receptor gene. Five mutations at this locus have been identified in French-Canadians. In children, it may be difficult to clinically distinguish FH from other forms of polygenic or monogenic hyperlipidemia. Therefore, our objectives were to define the molecular basis of our subjects' hypercholesterolemia, to characterize their biochemical phenotype in relation to the underlying molecular defect, and to assess their response to chronic dietary therapy. METHODS: We studied 88 unrelated French-Canadian children with a persistent increase in LDL cholesterol and a parental history of hyperlipidemia. Baseline and end-of-diet lipid and apolipoprotein levels were measured. Mutational analysis at the LDL receptor gene locus was performed. RESULTS: Heterozygosity for the common French-Canadian LDL receptor gene > 10-kb deletion was found in 57% of subjects (group 1), 14% carried one of the other four previously characterized LDL receptor gene mutations (group 2), and none of the five molecular defects tested was detected in 29% (group 3). Total cholesterol, LDL cholesterol, and apolipoprotein B baseline levels were similar among these three groups but significantly higher than in control subjects. However, there was wide interindividual variability even among those carrying the same mutation. Significantly lower baseline levels of high-density lipoprotein cholesterol and apolipoprotein A1 were found in group 1 compared with group 3 and the controls. The response to diet was similar among the three groups with an average reduction in the mean level of total cholesterol of 4.4%. CONCLUSIONS: The frequency of proven FH heterozygotes (71%) was remarkable in the pediatric population studied. Our data suggest that, in children, a persistent primary increase in LDL cholesterol associated with a parental history of hyperlipidemia is a good predictor of an underlying monogenic disorder as opposed to a polygenic disorder, at least in French-Canadians. Only molecular analysis allowed us to unequivocally define the cause of our patients' hypercholesterolemia. Most children with familial hyperlipidemia did not reach desirable plasma lipid levels solely under diet therapy.

Adolescent↗
PubMed1994

Radiotherapy in the management of epidemic Kaposi's sarcoma.

PURPOSE: This study is presented to help define the role of radiotherapy in the management of epidemic Kaposi's sarcoma. METHODS AND MATERIALS: Between June 1986 and June 1993, we treated 453 patients who had acquired immunodeficiency syndrome related Kaposi's sarcoma. Two hundred fifty-two patients (55.6%) had received previous treatment for their Kaposi's sarcoma: 228 (55.3%) with interferon, and 116 (25.6%) with Vinblastine. Depending on both tumour size and location, patients were treated with extended cutaneous irradiation using 4 MeV electron beam energy and/or localized irradiation using 45-100 kV x-ray (cutaneous lesions), or 4 MV x-ray (oral tumours). A total of 5015 courses of radiation therapy was given. The intention of the treatment was closely linked to the anatomic sites. Multiple courses of treatment ranging from 10 to 20 Gy (2.5 Gy/fraction, 4 times/week) were used for Kaposi's sarcoma involving conjunctiva (n = 32 treatments), eyelids (n = 306), lips (n = 170), hands (n = 208), feet (n = 417), penis (n = 131), oral mucosa (n = 43), and anal region (n = 5). A second group including other cutaneous sites (face, trunk, limbs) was treated with a dose of 30 Gy (20 Gy in 2 weeks followed by 2 weeks rest and then a second series of 10 Gy in 1 week). RESULTS: For the first group, tolerance was generally good excluding oral cavity irradiation, with an effective palliation of symptoms (87.8% overall rate of objective responses); an enhanced mucosal reactions was noted in patients receiving oropharyngeal irradiation. For the second group, a complete regression rate of 85% was observed; tolerance was acceptable: complications were severe epidermitis with skin ulceration (5%), exsudative epidermitis (26%), dry epidermitis (60%), and varying degrees of erythema (9%). There was a significant correlation between risk of recurrence (overall recurrence rate of 71% after an average of 7.5 months) and occurrence of opportunistic infections: 85% of recurrences appeared concomitantly with accelerated course of acquired immunodeficiency syndrome. CONCLUSIONS: We conclude that radiotherapy is an efficient treatment for epidemic Kaposi's sarcoma (EKS): doses of 15.2 Gy for oral lesions and 20 Gy for lesions involving conjunctiva, eyelids, lips, hands, feet, penis, and anal region were sufficient to produce shrinkage of the tumour and good palliation of symptoms. For the other cutaneous sites, 30 Gy local field irradiation could be safely given with better short-term response. Prophylactic measures with antifungal treatment should be systematically associated with oropharyngeal irradiation, to improve tolerance to the treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Apolipoprotein synthesis in human fetal intestine: regulation by epidermal growth factor.

In this investigation, human fetal intestine (17-20 wk) was used to study the synthesis of apolipoproteins (apo) A-I and B and its modulation by epidermal growth factor. Cultured jejunal explants were incubated with [3%S]-methionine, homogenized, immunoprecipitated and subjected to gel analysis. Radioactivity was detected mostly in apo A-I and, to a lesser extent, in both apo B-48 and apo B-100. However, apo B-48 was always the predominant form. The addition of EGF (100 ng/ml) resulted in a simultaneous decrease in apo B-100 synthesis and increase in apo B-48 production without a marked effect on apo A-I. Moreover, the incubation of jejunal explants with [14C] oleic acid documented the ability of fetal intestine to produce chylomicrons, VLDL, LDL and HDL. Therefore, the human fetal intestine has an efficient lipoprotein-lipid transport system and EGF is able to modulate levels of both apo B species as well as lipoprotein fractions.

Abortion, Legal↗