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Biomedical subjects

E Levy

Publications and source records attributed to E Levy.

At least 145 records · Page 8Linked to original sources
PubMed1994

Malondialdehyde-modified high-density lipoprotein cholesterol: plasma removal, tissue distribution and biliary sterol secretion in rats.

Evidence has been accumulating for the putative role of chemically or oxidatively altered lipoproteins in accelerating events in the atherogenic process. In this study, the movement of free cholesterol from native high density lipoprotein (HDL) and malondialdehyde (MDA)-modified HDL to the liver for biliary cholesterol secretion and bile acid transformation was examined in vivo. To this end, HDL from normal donor rats was isolated, conjugated with MDA, labelled with [14C]cholesterol and injected i.v. into rats with bile diversion. While the 6 h collection revealed no substantial differences in bile flow, less 14C excretion was recovered in the fresh bile of animals receiving MDA-modified HDL. Bile analysis indicated that a significant decline in labelled bile acid secretion characterized these rats. Compared with controls, MDA-modified HDL also caused an enhanced accumulation of [14C]cholesterol in the liver and the kidneys, with reduced delivery to the sites of steroidogenesis, i.e., the adrenals and testes. No plasma removal differences were noted in the HDL of both groups of rats. Thus, modification of HDL by MDA seems to impair the tissue distribution of its cholesterol moiety, particularly in the liver, where it accumulates at the expense of bile acid transformation.

Animals↗
PubMed1994

[Surgery of acute necrotizing pancreatitis. Active prolonged drainage in 157 consecutive patients].

OBJECTIVES: Conventional surgery and non-surgical methods have given unsatisfactory results for the treatment of acute necrotic pancreatitis. We therefore adoptive active prolonged drainage with the aim of controlling both acute enzyme toxicity and secondary necrosis. METHODS: One hundred fifty-seven patients with necrotic pancreatitis defined as the presence of extensive pancreatic or peripancreatic necrosis at laparotomy were divided into three groups according to previous care: group 1 no prior medical or surgical treatment (n = 46, 29%), group 2 prior medical but no surgical treatment (n = 48, 31%) and group 3 prior medical and surgical treatment (n = 63, 40%). Spiral drains were placed in the drainage grooves after necrosectomy and post-operative drainage with Mikulicz bags. Continuous lavage-drainage was then maintained for 45 days. Enteral nutrition was initiated on day 7 (mean) and increased progressively to 75 kcal/kg/day so parenteral nutrition could be interrupted 8 days later. RESULTS: There were 28 deaths (18%) including 6 in group 1, 10 in group 2 and 12 in group 3 (13, 21 and 19% respectively). Deaths were due to early multiple organ failure (n = 16), progressive degradation of the clinical situation (n = 8) and sudden death despite improvement (n = 4). Complications requiring re-operation occurred in 44 patients (28%). Among the 129 survivors, mean duration of hospitalization was 70 days including 60 days in the intensive care unit. CONCLUSIONS: Compared with results from former series, active prolonged drainage appears to be more adapted to the natural history and anatomic presentation of acute necrotic pancreatitis.

Acute Disease↗
PubMed1994

Differential structural requirements of heparin and heparan sulfate proteoglycans that promote binding of basic fibroblast growth factor to its receptor.

Heparan sulfate proteoglycans (HSPG) are obligatory for receptor binding and mitogenic activity of basic fibroblast growth factor (bFGF). The capacity of various species of heparin and heparan sulfate (HS) to promote bFGF receptor binding was investigated using both Chinese hamster ovary mutant cells deficient in cell surface HSPG and a soluble bFGF receptor-alkaline phosphatase fusion protein. Highly sulfated oligosaccharides were more effective than medium and low sulfate fractions of the same size oligosaccharide. O-Sulfation in heparin was found to be critical for its capacity to promote binding of bFGF to its receptors. The highest level of bFGF-receptor binding was achieved in the presence of over-sulfated heparin fragments (% sulfur > 14) regardless of whether the N-position was sulfated or acetylated. Unlike receptor binding of bFGF which requires oligosaccharides containing at least 8-10 sugar units, displacement of heparin- or HS-bound bFGF was obtained by oligosaccharides containing as little as four sugar units and by an N-sulfated, O-desulfated heparin fragment (% sulfur = 5.3). A preparation of total cell surface-derived HS induced bFGF receptor binding. A preliminary survey of several defined and affinity purified species of cell surface HSPG, including syndecan, fibroglycan, and glypican failed to identify natural HSPG that promote high affinity receptor binding of bFGF. A similar lack of activity was observed with species of HS isolated from bovine arterial tissue and characterized for their effect on vascular smooth muscle cell proliferation. Moreover, most of these species of HS inhibited in a dose-dependent manner the restoration of bFGF-receptor binding induced by heparin or by total HSPG. These results suggest the involvement of defined heparin-like oligosaccharide sequences and unique species of cell surface and extracellular matrix HS in the regulation of bFGF receptor binding and biological activity.

Animals↗
PubMed1994

Apoprotein B structure and receptor recognition of triglyceride-rich low density lipoprotein (LDL) is modified in small LDL but not in triglyceride-rich LDL of normal size.

We compared the effect of lipid composition and particle size of triglyceride-rich low density lipoprotein (LDL) upon apoprotein B conformation and binding to the LDL receptor. Three groups of triglyceride-rich LDL were studied: (a) LDL isolated from chronic hypertriglyceridemic individuals (HTG-LDL); (b) normal LDL made triglyceride-rich by in vitro incubation with triglyceride emulsion and the neutral lipid transfer protein (R-LDL); and (c) LDL from normolipidemic individuals made acutely hypertriglyceridemic by intravenous infusion of 10% Intralipid (IV-LDL). HTG-LDL was small and dense, whereas R-LDL and IV-LDL had normal size. HTG-LDL, but not R-LDL or IV-LDL, exhibited decreased binding to the LDL receptor on human skin fibroblasts in studies at 4 degrees C and reduced degradation at 37 degrees C. Apoprotein B conformation was assessed by circular dichroism and by analyzing the immunoreactivity of different monoclonal antibodies. HTG-LDL but not R-LDL or IV-LDL showed a change in the CD spectra and a consistent decrease in the immunoreactivity of monoclonal antibody 3F5 (2.5-fold) which recognizes an epitope adjacent to the receptor binding domain of apoprotein B. These findings suggest that in triglyceride-rich LDL, the relative content of neutral lipid in the core of LDL in the absence of changes in the size of the particle does not significantly affect apoprotein B conformation or its affinity for the LDL receptor.

Antibodies, Monoclonal↗
PubMed1994

Chromosome 14-encoded Alzheimer's disease: genetic and clinicopathological description.

A family of Finnish descent with very-early-onset Alzheimer's disease has been identified. Genetic analysis of this family eliminated the amyloid precursor protein gene as the pathogenic locus, but strongly implicated a locus on chromosome 14q23.4 between D14S52 and D14S55. The early age at onset of the disease (average, 36 years; range, 35-39 years), the rapid progression, and the early and prominent myoclonus, while they appear to be frequent findings in the chromosome 14-encoded form of Alzheimer's disease, raised the clinical suspicion of prion disease. However, sequencing the prion gene-coding region of 2 affected members of the pedigree failed to show any abnormality. Apart from the presence of modest cortical vacuolar change, the pathological features of our index patient appeared typical of Alzheimer's disease with abundant senile plaques immunoreactive with beta-amyloid, but not with prion protein antibodies.

Adult↗
PubMed1994

The cost of treatment dropout in depression. A cost-benefit analysis of fluoxetine vs. tricyclics.

In this study, we tried to estimate the economic potential benefit of the use of fluoxetine (PROZACR 20 mg, Lilly) versus tricyclic antidepressants (TCAs) in depression of mild to moderate intensity. Fluoxetine has demonstrated, in controlled studies, significantly lower rates of side-effects and treatment dropout than TCAs while showing similar efficacy. Treatment dropout, especially at an early stage of the therapy, can have profound consequences, including excessive lengthening of the depressive episode, symptomatic relapse, increase of repeated days out of work, even suicides or suicide attempts. We estimated the expected cost of treatment dropout using a Delphi expert panel. We then computed the economic benefit of fluoxetine by combining the dropout cost and the differential rate of total treatment dropout between fluoxetine and TCAs, as found in clinical trials. We thus showed that a 8 week fluoxetine could be beneficial to society provided society values a year of human life above a threshold varying from French Francs 23.800 to FF8.600 (respectively, about US$4500 and 1600) depending on the type of depression. As these values are extremely low compared to those found in the literature, we concluded that an apparently costly innovation such as fluoxetine may induce short-term financial savings for society.

Antidepressive Agents, Tricyclic↗
PubMed1994

Words in discourse: a dialectical approach to the acquisition of meaning and use.

Word learning by young children is viewed as a problem of deriving meaning from the use of forms in discourse contexts. Uses of causal and temporal terms in private speech by a child studied longitudinally from 1;9 to 3;0 are analysed from this perspective. Evidence is presented that words are first constrained to uses in specific discourse contexts, and later used more flexibly and with greater control over the semantics of the terms. Derivation of meaning from discourse is described as a dialectical process, and as such it is claimed to be more consistent with the full range of observational data, and with theories of word learning applicable to older children and adults, than other current theories of lexical acquisition in early childhood.

Child, Preschool↗
PubMed1994

(+)-(S)-dihydroaeruginoic acid, an inhibitor of Septoria tritici and other phytopathogenic fungi and bacteria, produced by Pseudomonas fluorescens.

Three antibiotics were isolated from a CH2Cl2 extract of the liquid culture of Pseudomonas fluorescens strain PFM2. Two of the antibiotics were identified as 2,4-diacetylphloroglucinol and pyoluterin. The structure elucidation, absolute stereochemistry, synthesis, and biological activities of the new antibiotic (+)-(S)- dihydroaeruginoic acid [1] are reported.

Anti-Bacterial Agents↗
PubMed1994

Activated ras oncogene and specifically acquired resistance to cisplatin in human mammary epithelial cells: induction of DNA cross-links and their repair.

A human non-malignant mammary epithelial cell line, HBL100, and the ras-transformed HBL100/ras1 cell line were examined for their sensitivity to cis-diamminedichloroplatinum(II) (cisplatin). The clonogenic cell survival assay showed that HBL100/ras1 exhibited a 2.7-fold increased resistance compared to the parental HBL100 cell line. The responses to other agents interacting with DNA, such as mitomycin C, 8-methoxypsoralen plus UVA or doxorubicin, were very similar in both cell lines. The same is true for ionizing radiation (Alapetite et al., Int J. Radiat. Biol., 59, 385-396, 1991). In other words, the mechanism of acquired resistance in HBL100 appears to be limited to cisplatin. No difference was observed between the two cell lines in cisplatin uptake as determined by atomic absorption spectrometry. Alkaline elution showed that less interstrand cross-links were formed by this drug in the resistant HBL100/ras1 cells compared to HBL100 and, moreover, the removal of these adducts was clearly more efficient in the former cell line. This was confirmed by an in vitro excision repair assay which revealed a 2.2-fold increase in DNA repair activity in the extracts from HBL100/ras1 versus HBL100 cells. It is concluded that the transformation of human epithelial HBL100 cells by the ras gene resulted in an acquired resistance apparently limited to cisplatin, a feature associated with a reduced proportion of induced interstrand cross-links and a higher efficiency in their removal. The mechanism of involvement of the ras gene product in this process is still a matter of speculation.

Breast↗
PubMed1994

Lipid esterification and synthesis by the IEC-6 intestinal epithelial crypt cell line: effect of transforming growth factor beta.

The capacity of immature intestinal epithelial crypt cells to synthesize lipids and the factors that promote their differentiation remain largely unknown. We examined the profile of lipids synthesized by a normal rat intestinal epithelial crypt cell line (IEC-6) and determined the effects of transforming growth factor beta (TGF beta), a putative crypt cell differentiating factor, on their lipid handling. Incubation of IEC-6 cells with [14C]oleic acid (20 h) resulted in lipid esterification and synthesis, mainly as triglycerides (TGs, 57 +/- 0.6%) and phospholipids (PLs, 30 +/- 0.6%), with a PL/TG ratio of 0.53. When cells were pulsed (2.5 h) with [14C]oleic acid and then maintained 20 h in medium alone, a significant elevation of the PL/TG ratio (10.2 +/- 1.3, p < 0.01) was observed, primarily accounted for by a significant decrease of the TG fraction (p < 0.01). IEC-6 cells secreted only trace amounts of lipids under the latter experimental condition. Incubation with TGF beta (20 h) significantly inhibited IEC-6 cell proliferation but did not promote the expression of cell sucrase activity. TGF beta induced a significant increase in the cellular composition of PL (p < 0.05) and a decrease in the TG fraction (p < 0.02), after a 2.5-h pulse of [14C]oleic acid. Lipid production was unaffected by TGF beta during the 20-h incubation with [14C]oleic acid. Lipid secretion into the medium remained negligible in the presence of TGF beta, after 2.5 h of incubation with substrate as above. Our findings suggest that immature crypt IEC-6 cells are capable of lipid esterification and synthesis but secrete minute amounts of lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Variable expression of familial heterozygous hypobetalipoproteinemia: transient malabsorption during infancy.

Rare instances of symptomatic fat malabsorption have been reported in patients with heterozygous hypobetalipoproteinemia, but with an unclear pathogenesis. An 8-month-old boy with chronic diarrhea and failure to thrive was found to have abnormally low plasma total cholesterol (85 mg/dl), LDL-cholesterol (48 mg/dl), apoB (52 mg/dl), apoA-I (53 mg/dl), and vitamin E (0.22 mg/dl). Decreased plasma LDL-C and apoB were noted in the father (34 and 40 mg/dl, respectively), as well as several other family members. Fasting triglycerides were normal but did not increase normally in response to a fat meal test. Lipoprotein composition showed an abnormal profile of very low density (VLDL, d 1.006 g/ml), low density (LDL, d 1.063 g/ml), and high density (HDL, d 1.21 g/ml) lipoproteins. A fasting jejunal biopsy revealed lipid-laden enterocytes. Electron microscopy of the jejunal biopsy revealed the absence of lipid particles in the intercellular spaces after a fat meal. Jejunal explants cultured with [14C]palmitate and [3H]leucine showed limited synthesis of triglycerides and apolipoproteins (36 and 42% of controls, respectively), whereas the father's results were close to normal. At 1 year of age, improvement in intestinal fat absorption was accompanied by the presence of chylomicrons in the intercellular space, concomitant with the enhanced synthesis of lipids and apoB by jejunal explants. These data provide evidence that heterozygous hypobetalipoproteinemia may present early in life as transient, symptomatic lipid malabsorption. The mechanisms responsible for improved lipid transport despite persistent hypobetalipoproteinemia remain to be established.

Apolipoproteins B↗
PubMed1993

Previous subtotal colectomy with ileostomy and sigmoidostomy improves the morbidity and early functional results after ileal pouch-anal anastomosis in ulcerative colitis.

The aim of this work was to study the effects of previous subtotal colectomy (STC) with ileostomy and sigmoidostomy on the outcome of ileal J-pouch-anal anastomosis (IPAA) in patients with acute ulcerative colitis. Between 1983 and 1991, we conducted a prospective, nonrandomized study of 156 patients who underwent IPAA in our center. Fifty-five patients (34.3 percent) had undergone STC with ileostomy and sigmoidostomy for either severe acute colitis (36.5 percent of cases) or nonresolving acute colitis (63.5 percent) up to six months before IPAA with covering ileostomy. There were no perioperative deaths; six patients (11 percent) developed complications requiring reoperation (three cases of pelvic sepsis, two occlusions, and one stenosis of the ileostomy). IPAA was successfully carried out at a later stage in all cases. The results of IPAA in these patients were compared with those in 78 patients who underwent the classical two-stage IPAA procedure. The rates of pelvic sepsis and postoperative occlusion were lower in the subgroup of patients who underwent the three-step procedure. Three months after closure of the ileostomy, the mean number of daily stools was significantly lower in the patients who had undergone prior STC (5.09 vs. 5.9), but there was no significant difference between the two groups with regard to diurnal and nocturnal continence, the need to wear a pad, discrimination between gas and stools, or the use of antidiarrheal medication. In addition, there was no significant difference at one year in terms of functional parameters. We conclude that STC is a simple and safe procedure for the treatment of a severe attack of colitis and that it does not compromise the results of later IPAA. Because it does not increase the morbidity of subsequent IPAA and is associated with more rapid functional recovery, STC appears to be suitable for the treatment of patients with nonresolving acute colitis before the onset of malnutrition or steroid dependency.

Adolescent↗
PubMed1993

Risk of another basal cell carcinoma developing after treatment of a basal cell carcinoma.

BACKGROUND: There is an increased risk of new basal cell carcinomas (BCCs) developing in a person who has had a BCC. OBJECTIVE: This study attempts to define the magnitude of this increased risk. METHODS: The charts of 260 white patients with a histologically proven BCC were reviewed for the occurrence of new BCCs. The cumulative 5-year incidence (modified life-table method) for new BCCs developing in these patients was compared with the 5-year incidence in the general white population of the United States. RESULTS: Of the 260 patients, new BCCs developed in 137 within an average of 38.3 months, a 5-year cumulative rate of one or more new BCCs of 45.2%. The yearly risk for new BCCs developing in the study population remained high during the 5-year interval. In the general white population of the United States, the maximal 5-year incidence was calculated to be 5% (p < 0.005, chi-square test). CONCLUSION: Patients with a history of BCC require life-long follow-up because of the high probability of new BCCs developing.

Aged↗
PubMed1993

Beneficial effects of fish-oil supplements on lipids, lipoproteins, and lipoprotein lipase in patients with glycogen storage disease type I.

Glycogen storage disease type I (GSD-I) is frequently complicated by severe hyperlipoproteinemia and the increased potential risk of premature atherosclerosis. The effects of fish-oil supplementation [MaxEPA, 10 g.(1.73 m2)-1 for 3 mo] were investigated prospectively in seven hyperlipoproteinemic patients with GSD-I. Hypertriglyceridemia and hypercholesterolemia improved after 3 mo of fish-oil treatment, decreasing 49% (P < 0.005) and 23%, respectively. This was accompanied by a reduction in both low-density-lipoprotein (LDL) cholesterol (25%, P < 0.03) and apolipoprotein B (40%) and by increased high-density-lipoprotein increased (HDL) cholesterol (30%, P < 0.002) and apolipoprotein A-I (31%, P < 0.05). Low pretreatment ratios of HDL to total cholesterol and HDL to LDL, indicators of elevated atherosclerosis risk, increased significantly (P < 0.05). Plasma lipoprotein profile as well as lipoprotein composition [triglyceride (TG) enrichment and cholesteryl depletion] improved. Reduced TG concentrations were due to enhanced fat catabolism, as evidenced by the significantly increased hepatic and extrahepatic lipoprotein lipase activity (P < 0.05). Withdrawal of fish oil for 3 mo was associated with a return to pretreatment abnormalities in plasma lipids and lipoproteins. Fish-oil supplementation thus improves the hyperlipoproteinemia in GSD-I and may significantly reduce the risk of premature atherosclerotic cardiovascular disease.

Adolescent↗
PubMed1993

Circulating tumor necrosis factor-alpha levels and lipid abnormalities in patients with cystic fibrosis.

Hyperlipidemia is prominent among the disturbances in intermediary metabolism that occur subsequent to infections by microorganisms. The response to such infections is known to involve several cell types and is mediated by cytokines. We hypothesized that metabolic lipid disturbances seen during infection in cystic fibrosis (CF) patients may partly be the result of excessive tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine known to cause a large spectrum of pathophysiologic alterations, including impaired lipid metabolism. Therefore, we determined the circulating concentration of TNF-alpha and analyzed its relationship to lipid and lipoprotein levels, as well as lipoprotein lipase activity, in 31 CF patients. Plasma TNF-alpha values were significantly (p < 0.01) elevated in patients with CF compared with controls. The CF subjects were found to have decreased plasma cholesterol (25%), LDL cholesterol (35%), and HDL cholesterol (19%) concentrations, whereas plasma triglycerides were significantly increased (p < 0.001). The apo A-I level was reduced (p < 0.005), whereas apo B levels were normal. Low levels of the major essential fatty acids were found in the plasma of the CF patients, and the triene/tetraene ratio confirmed their essential fatty acid deficiency. Postheparin lipolytic activity was lower in CF patients than in controls, and the decreased activity was accounted for primarily by a decline in hepatic lipase. A significant positive correlation (p < 0.001, r = 0.70) was found between TNF-alpha and plasma triglyceride levels. However, no association was noted between TNF-alpha and essential fatty acid, cholesterol, or lipoprotein cholesterol levels, or with lipoprotein lipase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗