Biomedical subjects

E Levy

Publications and source records attributed to E Levy.

At least 19 recordsLinked to original sources

PubMed1992

Insulin decreases chylomicron production in human fetal small intestine.

The objective of this study was to examine the effect of insulin on lipoprotein synthesis and secretion in human fetal intestine. Jejunal explants were cultured with [14C]oleic acid in Leibovitz medium for 42 h. Although the addition of insulin (30 U) did not alter the incorporation of [14C]oleic acid into triglycerides, phospholipids and cholesteryl esters in the tissue, it significantly decreased (P < 0.05) the level of triglycerides (20%) in the medium. Among the three lipoprotein classes (chylomicron, VLDL, and HDL) isolated by ultracentrifugation, the chylomicron level was found significantly (P < 0.05) diminished in the medium (29%). Neither the lipid chemical composition of CM or that of VLDL, LDL and HDL was affected by the presence of insulin. These results suggest that chylomicron synthesis is modulated by insulin, whereas lipoprotein distribution and lipid composition are not regulated by this hormone.

Chylomicrons↗

PubMed1992

[Colonic complications of acute necrotizing pancreatitis].

Among 126 patients operated upon for acute necrotizing pancreatitis in our department over a 10-year period starting in November 1979, 17 had a colonic resection. Colectomy was made mandatory by a necrotic or ischaemic appearance (12 cases, including 3 bowel perforations), an isolated perforation (2 cases) or extensive fat necrosis of the pericolonic atmosphere (3 cases). The hospital mortality was 5 out of the 17 cases. In 6 patients, the pathological results suggested that colonic resection was unnecessary. Since May 1988, a diverting loop ileostomy has been performed whenever colonic viability was found to be dubious at laparotomy. After this policy was introduced no case of secondary colonic complication was encountered. Nevertheless, there still are "abusive" colectomies unjustified by the pathology. Their number should be reduced by a more cautious indication of colonic resection in acute necrotizing pancreatitis.

Acute Disease↗

PubMed1992

Gelsolin gene mutation--at codon 187--in familial amyloidosis, Finnish: DNA-diagnostic assay.

Familial amyloidosis, Finnish (FAF), is an autosomal dominant form of systemic amyloidosis with lattice corneal dystrophy and progressive cranial neuropathy as principal clinical manifestations. We have shown that the novel amyloid fibril protein found in these patients is an internal degradation fragment of gelsolin, an actin-binding protein, and that it contains an amino acid substitution, asparagine for aspartic acid at position 15, that is due to a guanine-to-adenine transversion corresponding to codon 187 of human plasma gelsolin cDNA. To test that this mutation cosegregates with the disease high-molecular-weight genomic DNA was isolated from autopsied tissues or lymphocytes of 23 patients, 6 healthy relatives and 20 unrelated healthy control persons. Specific fragments were amplified with the polymerase chain reaction for oligonucleotide hybridization analysis using the slot-blot technique. The guanine-to-adenine transversion was found in all FAF patients tested, but in none of the control subjects. Our results show that the mutation (G to A) cosegregates with the disease phenotype, and that the slot-blot analysis can be used as a diagnostic assay, including prenatal evaluation.

Amyloidosis↗

PubMed1992

Purification and characterization of a catalase-peroxidase from the fungus Septoria tritici.

Three classes of heme proteins, commonly designated hydroperoxidases, are involved in the metabolism of hydrogen peroxide: catalases, peroxidases, and catalase-peroxidases. While catalases and peroxidases are widely spread in animals, plants, and microorganisms, catalase-peroxidases were characterized only in prokaryotes. We report here, for the first time, on a catalase-peroxidase in a eukaryotic organism. The enzyme was purified from the fungal wheat pathogen Septoria tritici, and is one of three different hydroperoxidases synthesized by this organism. The S. tritici catalase-peroxidase, designated StCP, is similar to the enzymes previously isolated from the bacteria Rhodobacter capsulatus, Escherichia coli, and Klebsiella pneumoniae, although it is significantly more sensitive to denaturing conditions. In addition to its catalatic activity StCP catalyzes peroxidatic activity with o-dianisidine, diaminobenzidine, pyrogallol, NADH, and NADPH as electron donors. The enzyme is a tetramer with identical subunits of 61,000 Da molecular weight. StCP shows a typical high-spin ferric heme spectrum with a Soret band at 405 nm and a peak at 632 nm, and binding of cyanide causes a shift of the Soret band to 421 nm, the appearance of a peak at 537 nm, and abolition of the peak at 632 nm. Reduction with dithionite results in a decrease in the intensity of the Soret band and its shift to 436 nm, and in the appearance of a peak at 552 nm. The pH optimum is 6-6.5 and 5.4 for the catalatic and peroxidatic activities, respectively. Fifty percent of the apparent maximal activity is reached at 3.4 mM and 0.26 mM for the catalatic and peroxidatic activities, respectively. The enzyme is inactivated by ethanol/chloroform, and is inhibited by KCN and NaN3, but not by the typical catalase inhibitor 3-amino-1,2,4-triazole.

Catalase↗

PubMed1992

Induction of B16 melanoma melanogenesis by a serum-free synthetic medium.

Cultured murine B16 melanoma cells normally grow as spindle-shaped cells firmly attached to tissue culture flasks. Pellets obtained from harvested B16 melanoma cells are white to grey in color. When the same cells were grown in synthetic, serum-free AIM V medium, cellular morphology and pigmentation were radically altered. Within 3 days of subculture in AIM V, cells rounded up and grew in clusters in suspension. Melanin content increased to greater than 30 times and tyrosinase activity was found to be 10-50 times higher in cells grown in AIM V medium compared to those cultured in normal medium. A concomitant increase in the level of immunoreactive tyrosinase was also induced. The individual growth factors and hormones present in AIM V medium were examined to determine which component(s) stimulates melanogenesis. Only those cells grown in the presence of 2.5% human albumin were stimulated to synthesize melanin. These findings suggest that albumin, or a component associated with albumin, has a major effect upon the regulation of melanogenesis in these cells.

Animals↗

PubMed1992

The serum lipoprotein profile in veterans with paraplegia: the relationship to nutritional factors and body mass index.

Individuals with spinal cord injury have a shortened life expectancy, with coronary heart disease as a leading cause of death. Identifying potentially reversible risk factors would be expected to be of value in the long-term care of the person with a spinal cord injury. We addressed the relationships among diet, body mass index, and serum lipid levels in 28 veterans with paraplegia compared to 52 age-matched ambulatory veteran controls. There are no significant differences in body mass index or in total caloric, saturated fat, or cholesterol intake between those with paraplegia and the control group. The serum HDL cholesterol level is significantly lower in those with paraplegia compared to the control group (35 +/- 2 vs 49 +/- 2 mg/dL). There are no significant differences noted in serum total cholesterol, LDL cholesterol, or triglycerides between the groups. Total caloric intake decreases significantly with age in the control subjects but not in the subjects with paraplegia. Inverse correlations are found between serum HDL cholesterol and serum triglycerides levels both in those with paraplegia (r = -0.54, p less than 0.005) and in the controls (r = -0.42, p less than 0.001). In our group of subjects with paraplegia, serum lipid levels appear to be independent of dietary intake and body weight.

Adult↗

PubMed1992

Drug use and abuse in an urban veteran spinal cord injured population.

Substance abuse in the spinal cord injured (SCI) population has been addressed in a few controlled studies. These reports have led to the belief that many SCI patients were illicit drug users prior to their injury and that their drug abuse was a contributing cause of their accidents. One large study determined from answers obtained on a questionnaire that drug abuse, other than alcohol, was prevalent among injured veterans. Our study uses urine toxicology to determine the frequency of drug use and abuse, excluding alcohol, in 72 inpatients and 81 outpatients associated with an urban Veterans Affairs Medical Center. In a blinded experiment, urinary concentrations of opiates, barbiturates, amphetamines, methadone, benzodiazepines, and cocaine were determined with Syva reagents on an Abbott VP. Urinary cannabinoids were determined using Abbott TDX and the FPIA method. The use of illicit (unprescribed) drugs was surprisingly low (< or = 13 percent) for an urban medical center. Outpatient cannabinoid abuse was significantly more frequent than inpatient usage (p < 0.01). Barbiturates were not found in any patient. Benzodiazepines were taken most commonly (29 percent). Since benzodiazepine usage is the direct result of physician prescription, wide-spread usage of this agent is avoidable. Physicians should pay attention to the probable deleterious consequences of benzodiazepine addiction related to depressive effects on the central nervous system caused by its chronic use.

Adult↗

PubMed1992

T lymphocyte expression of complement receptor 2 (CR2/CD21): a role in adhesive cell-cell interactions and dysregulation in a patient with systemic lupus erythematosus (SLE).

Complement receptor 2 (CR2, CD21), the receptor for both the C3d,g portion of human complement component C3 and the Epstein-Barr virus, has been recently described on peripheral T cells. By using dual stain flow cytometric analysis, we have also observed that a peripheral T lymphocyte subpopulation of normal healthy donors bears CR2 in a range varying from 1.1 to 23.2% (mean 12.6%) of total CD3+ cells. T lymphocytes from nine patients with inactive SLE expressed CR2 in a similar range. Three patients with active SLE were also studied. One of them, having neuropathy and glomerulonephritis, displayed an expansion of the CR2 T cell subpopulation which reached as much as 89% of total CD3+ cells. To examine potential functional roles of T cell CR2, cells from a Jurkat-derived CR2 expressing T cell line were found to bind in vitro to human CR2-, complement-coated K562 cell targets in a CR2- and complement-dependent fashion. Based on these studies, we hypothesize that CR2 might act to increase adherence of T cells to nucleated target cells bearing C3d,g, a function which may be relevant to cytotoxicity or other T cell activities requiring cell-cell interaction.

B-Lymphocytes↗

PubMed1992

The ontogeny and site of intestinal lipid and lipoprotein synthesis.

The developmental aspects of characteristic intestinal lipoprotein synthesis, chlomicrons (CM), very low density lipoproteins (VLDL) and high density lipoproteins (HDL), are unknown. Our objective was to determine the ontogeny of intestinal lipid and lipoprotein synthesis in both the jejunum and the ileum. Explants of the jejunum and the ileum from fetal (F) (18-19 days of gestation), suckling (S) (5 days old) and weaning (W) (23 days old) rats were cultured in the presence of [14C]-oleic acid to examine lipid synthesis. The results indicate the following. (1) The incorporation of oleic acid is higher for the fetal explants. However, the efficiency of esterification of free fatty acids (FFA) into triglycerides (TG) in the jejunum increases with age (33% F, 37% S, 48% W) (P less than 0.05, by ANOVA). (2) The same profile is found at the ideal site for the incorporation of oleic acid. However, the capacity for the synthesis of TG is more intense at the suckling period (34% F, 54% S, 42% W) (P less than 0.05, by ANOVA). (3) The relative content of TG in CM changes with age: F, 90-93%; S, 80-84%; W, 33-40%. (4) A low percentage of TG content is found in CM at the weaning period while high levels are detectable in VLDL (40-42%). (5) A most significant difference is noted between the jejunum and the ileum in TG synthesis at the suckling period. The ileum synthesizes 53% more TG than the jejunum (P less than 0.025). (6) HDL particles contain substantial amounts of FFA. Nevertheless, they were also found to be able to transport TG mainly in the suckling rat. Thus, this study demonstrates that with growth the rat is able to synthesize CM, VLDL and HDL. Our findings indicate changes in the synthesis of intestinal lipids and lipoproteins, depending on both the development and the site, which suggests an ontogeny. These modifications can be attributed to dietary and hormonal influences present during the period of development.

Animals↗

PubMed1992

Localised deep microwave hyperthermia in the treatment of benign prostatic hyperplasia: long-term assessment.

A group of 133 patients with benign prostatic hyperplasia who were either poor operative risks or who had refused surgery underwent localised deep microwave hyperthermia, without supplementary drugs. In 59% of patients who had had an indwelling catheter, freedom from urological obstruction and satisfactory voiding were maintained for 7 years and catheterisation was not required. In patients with severe prostatic symptoms, 65% showed general improvement and satisfactory voiding for 8 years. There were no side effects. Patients who relapsed were given a second course of treatment and 75% responded positively. This positive response and the lack of side effects suggest that localised deep microwave hyperthermia may be an effective alternative to surgery in the management of high risk patients and those who are reluctant to undergo surgery.

Aged↗

PubMed1992

The 1991 Borden Award Lecture. Selected aspects of intraluminal and intracellular phases of intestinal fat absorption.

The recognition of chylomicrons as dietary lipid transporters dates back to more than 70 years and marks a milestone in lipoprotein history. Conventionally, three phases constitute the process of absorption of exogenous fat: intraluminal, intestinal, and delivery. The intraluminal phase includes chemical hydrolysis by lipolytic enzymes and the micellar solubilization of lipolytic products by bile acids. The intestinal phase comprises the diffusion of micelles through the unstirred water layer, passive diffusion across the microvillous membrane of the enterocyte, and the formation of lipid-carrying lipoproteins. The delivery phase involves the exocytosis of chylomicrons from the absorptive cells and their subsequent removal by lymphatic structures and the systemic circulation. The precise steps and factors involved in all phases of chylomicron synthesis are not yet known, but both experimental and clinical studies have been helpful. Of the inborn metabolic disorders, the prerequisite function of apolipoprotein (apo B) for the assembly and release of lipoprotein particles stood out. Moreover, evidence emerged that the enterocyte produces apo B-100 in addition to apo B-48. Calcium and essential fatty acid status originates as determinants for triglyceride-rich particle synthesis. Furthermore, the developmental changes and regulatory factors of lipoprotein elaboration represent excellent tools in the study of the intracellular mechanisms of lipid transport.

Animals↗

PubMed1992

Intraluminal and intracellular phases of fat absorption are impaired in essential fatty acid deficiency.

The structure and function of enterocyte membranes are particularly sensitive to the degree of fatty acid saturation. The objective of the present study was to assess intestinal fat transport in essential fatty acid (EFA)-deficient animal models. Both the digestive and absorptive phases leading to the formation and the secretion of triglyceride (TG)-rich lipoproteins were investigated. After an intraduodenal fat infusion, the percentage increase of plasma TG over fasting values was examined over a period of 4 h in two groups of control and EFA-deficient rats. Lower values at 1 and 2 h (P less than 0.05) were observed in EFA-deficient rats, suggesting fat malabsorption. Likewise, postprandial chylomicronemia was diminished. In a separate group of rats, EFA deficiency was associated with reduced TG and chylomicron-TG transport into lymph. Although pancreatic lipase activity did not change (47.1 vs. 46.2 mumol free fatty acids.mg protein-1.h-1), bile flow was decreased over the 8-h period of collection. Concomitantly, a significant decline (nmol.min-1.g liver-1, P less than 0.05) was discernible in the biliary secretory rate of bile salts (14.09 +/- 2.13 vs. 35.09 +/- 3.73), phospholipids (7.01 +/- 0.61 vs. 11.79 +/- 1.65) and cholesterol (0.19 +/- 0.01 vs. 0.83 +/- 0.06). In vitro studies, utilizing everted sacs incubated with mixed micelles, revealed that EFA-deficient jejunal segments of rats incorporated and esterified less [14C]oleic acid (21 and 32%, respectively). Moreover, the synthesis and secretion of TG-rich lipoproteins were found markedly reduced in mouse jejunal explant cultures. We conclude that EFA deficiency modifies both the intraluminal and intracellular phases of fat absorption.

Absorption↗

PubMed1992

Ontogeny of intestinal lipid and lipoprotein synthesis.

Despite increasing evidence that the fetal intestine produces apoproteins, there is limited knowledge about its ability to absorb fat. The present study focused on the intracellular processing of lipid formation and transport by lipoproteins in the developing fetus. Explants of fetal jejunum (14-20 weeks) were maintained in serum-free organ culture for 42 h with [14C]-oleate. Esterified lipids extracted from the tissue showed an abundance of phospholipids (PL; 54-77%), while those harvested from the medium displayed a predominance for triglycerides (TG; 68-73%). Only a minor percentage of radioactivity was recovered in cholesterol ester (CE) from the tissue (1.8-2.5%) or medium (1.3-2.5%). Separation of PL by thin-layer chromatography revealed a prevalence of phosphatidylcholine followed by phosphatidylethanolamine. Over the fetal period studied a trend towards increase was noted in TG, CE and most of the PL classes but not phosphatidylcholine. In parallel, we observed a progressive increase in these lipoprotein fractions produced by the fetal intestine during development, i.e., chylomicrons, very low-density lipoproteins and high-density lipoproteins. Our data stress not only the ability of the fetal intestine to absorb fat, but also the ontogenetic changes of lipid and lipoprotein synthesis.

Fetus↗

PubMed1992

The effect of a new calcium channel blocker (TA-3090) on lipoprotein profile and intestinal lipid handling in rodents.

Recent interest has focused on findings that drugs used to lower blood pressure may adversely modify plasma lipids and lipoprotein metabolism. This observation may explain why pharmacologic control of hypertension has failed to reduce the incidence of morbidity and mortality from coronary artery disease. The present study aims to evaluate the effect of TA-3090, a new calcium channel blocker, on fasting plasma lipids and lipoproteins, as well as on processes of intestinal fat absorption. Rats were treated by gavage with TA-3090 (10 mg/kg twice daily) for 4 days and compared with controls (n = 6 per group). Plasma cholesterol was increased in the treated group to (mean +/- SE) 74 +/- 2 vs 60 +/- 4 mg/dl (P less than 0.01), due mainly to an increased high density lipoprotein-cholesterol level (50 +/- 2 vs 37 +/- 3 mg/dl, P less than 0.005). Notably plasma triglycerides (TG) and low density lipoprotein-cholesterol were not significantly affected. Another group of TA-3090-treated animals was given an intraduodenal fat meal, and the rise in plasma TG and chylomicrons followed over 4 hr. Postprandial hypertriglyceridemia and chylomicronemia were significantly lower at 2 hr (P less than 0.05) and 3 hr (P less than 0.01) compared with controls. In a separate group of animals, the addition of TA-3090 to a 2% intralipid infusion intraduodenally was associated with significantly reduced TG and chylomicron-TG transport into lymph (P less than 0.05). Furthermore, experiments in rats pretreated with TA-3090 intraperitoneally and then given 2% intralipid intraduodenally were shown to have a significant decrease in mean flow rate (27%), TG transport (31%) and chylomicron-TG output (37%), when compared with controls. In vitro studies using jejunal organ culture to examine the effect of TA-3090 on intracellular lipid synthesis and secretion revealed that the addition of the drug to the medium resulted in significantly decreased TG synthesis and secretion. These data suggest that TA-3090 could be effective in increasing HDL-cholesterol and reducing postprandial chylomicronemia. Our findings support a role for TA-3090 directly on enterocyte absorption and/or intracellular lipid transport, and thus indicate the importance of intracellular calcium on these processes.

Animals↗

PubMed1992

[Ex situ-in vivo hepatic resection. Technique and initial results].

Extracorporeal liver surgery has been proposed with the aim to increase the resectability rate in patients with advanced tumors. In order to avoid the inherent section of the hepatic pedicle we propose ex situ-in vivo liver surgery. The surgical procedure comprises complete mobilization and exteriorization of the liver which is rocked on the axis of the porta hepatis following section of the hepatic veins. Protection of the liver parenchyma against prolonged ischemia is obtained through cold portal perfusion (UW solution) and the use of an heat exchanger on which liver resections and vascular procedures are performed. The procedure also encompasses the use of veno-venous bypass during liver vascular exclusion. This procedure was performed in 2 patients with tumoral invasion of the 3 main hepatic veins and in 1 patient whose hemangioma was surrounding the hepatocaval confluence. Duration of hypothermic ischemia was 205, 225 and 230 minutes respectively. Postoperative course was uneventful in the 3 cases with an hospital stay of 25, 28 and 18 days. Ex situ-in vivo liver surgery allows completion of a surgical treatment in patients whose tumor appears unresectable with the use of conventional technics. This procedure may constitute an alternative to liver transplantation in highly selected cases.

Female↗

PubMed1992

Intestinal lipids and lipoproteins in the human fetus: modulation by epidermal growth factor.

The aim of the present investigation was first, to examine the ability of human fetal intestine (17-20 wk) to incorporate fatty acid into esterified lipids; and second, to study in vitro lipoprotein synthesis and secretion by fetal explants, as well as the effect of epidermal growth factor (EGF) on these processes. Cultured fetal jejunal explants were incubated in Leibovitz medium for 42 h with [14C]oleate. Both triglycerides (TG) and phospholipids (PL) were the major labeled products. Whereas TG were predominant (80%) in the culture medium, PL accounted for more than 50% of total tissue lipids. More than 60% of the radioactivity in PL was associated with phosphatidylcholine. Some labeling (< 5%) was also recovered in the cholesteryl ester fraction. Active exocytosis was demonstrated by the accumulation of newly synthesized esterified lipids in the medium and the presence of lipoproteins in the basolateral membrane region and intercellular spaces. Most of the newly synthesized lipids were found in lipoproteins of d < 0.97 g/ml (51.2%) and d < 1.21 g/ml (39.3%), whereas the rest were recovered in d < 1.006 g/ml (9.8%) and 1.063 g/ml (5.6%). A similar trend characterized the lipoprotein secretion. The synthesis of the d < 0.97 g/ml fraction (30,653 +/- 4,122 dpm/mg protein) was significantly greater than the 1.006 g/ml fraction (5,897 +/- 1,734), P < 0.005. The secretion of d < 0.97 g/ml particles into the medium was also five fold higher than that of the d < 1.006 g/ml fraction (P < 0.01). The addition of EGF to the culture medium (25, 50, and 100 ng/ml) significantly enhanced the d < 0.97 g/ml lipoprotein secretion (25-40%) and decreased the d 1.006 g/ml and 1.063 g/ml fraction output. The lipid composition of these lipoprotein fractions was never altered by the presence of EGF, suggesting that the number of lipoprotein particles, rather than size, was modified by the growth factor. The present findings provide the first evidence that the human fetal intestine has the capacity to elaborate lipoprotein fractions for the transport of newly synthesized lipids. Furthermore, our data suggest that EGF, present in significant quantity in saliva, amniotic fluid, and bile, can modulate the release of TG-rich lipoproteins by fetal intestinal explants.

Epidermal Growth Factor↗

PubMed1992

[Anti-influenza vaccination for active persons (25-64 years): a cost-benefit study].

This paper is a specific cost-benefit study concerning 25-64 years people flu vaccination. For this active population the vaccination rate is only 12% and the cost of absenteeism is potentially high. To make the balance between prevention costs and (direct and indirect) avoided costs by the vaccine, we use a basic case with mean value parameters as: efficacy rate of vaccine, impact of epidemics, size of vaccinated population, immunization length and compensation rate of the so-called production losses. These parameters are then supposed to vary in a sensitivity analysis. In any case net benefit of vaccination appears, which size varies mainly in relation to epidemics and vaccinated population extents. But improvements are to be achieved for giving more precise values to "real" efficacy rate of vaccination and effective economic impact of absenteeism on production.

Absenteeism↗

PubMed1992

[Economic analysis of maintenance treatment with ranitidine 150 mg in duodenal ulcer].

While it is well-established that ranitidine 150 mg/day is effective in preventing recurrence and complications of duodenal ulcer, the economic impact of maintenance therapy is unknown. Socio-economic data, allowing to calculate the costs and cost-effectiveness ratio of intermittent and maintenance therapy, were prospectively obtained from a therapeutic trial in 399 duodenal ulcer patients (Mignon et al, Gastroenterol Clin Biol 1990;14:732-8). Visits and endoscopy investigations, work days lost, duration of hospital stay and drug consumption were recorded in both placebo (n = 202) and ranitidine (n = 197) groups. Each source of expenditure was evaluated using current fares and sales prices, from the point of view of both the collectivity and the French Health Care System. The costs of ranitidine strategy were less than the costs of placebo strategy, for the collectivity (2,031 and 2,823 FF per patient for one year, respectively) as well as for the French Health Care System (1,541 and 2,426 FF per patient per year, respectively). In the ranitidine group, expenditures were principally due to the drug (71%) and endoscopy investigation (24%). In the placebo group, endoscopy and hospital stay accounted for 50 and 39% of the expenses, respectively. The latter were due to the occurrence of complications in the placebo group. Sensitivity analysis disclosed that the results were unsensitive to the variations in cost hypotheses of the main expenditure sources. Cost/effectiveness analysis defined as cost per patient successfully treated showed that the cost of a "ranitidine strategy" was 2-3 times less than a "placebo strategy". Maintenance therapy for duodenal ulcer with ranitidine 150 mg/day for one year is less expensive and more cost-effective than intermittent treatment.

Cost of Illness↗