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Biomedical subjects

E Levy

Publications and source records attributed to E Levy.

At least 181 records · Page 10Linked to original sources

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↗

[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↗

[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↗

[Diverting loop ileostomy, effective prevention of colonic complications in necrotizing acute pancreatitis].

The operative diagnosis of colonic ischaemia in association with acute necrotizing pancreatitis (ANP) may be difficult in the absence of unequivocal transmural necrosis or perforation. We introduced in May 1988 a new policy whereby, when colonic viability was dubious, resection was avoided and a diverting loop ileostopy (DLI) was performed. If necrosectomy led to extensive mobilization of the splenic flexure with a capillary drainage system placed in close contact, a DLI was again performed. Colectomy was only performed for unequivocal transmural necrosis. Among 30 patients operated on for ANP, 12 underwent DLI. This policy allowed us to spare potentially ischaemic colons. No secondary colonic complication occurred and there was no rise in the mortality rate. Among patients whose colon was kept in circuit there were bouts of bowel distension and unexplained bacteriemia ultimately leading to death from multiorgan failure. When colonic viability is dubious and when drainage is brought up in close contact with the bowel wall DLI might allow colonic resection to be avoided. In our experience DLI also seemed to prevent secondary colonic complications.

Acute Disease↗

[Familial hypobetalipoproteinemia with steatorrhea and malabsorption].

In a family in which the father was the mother's uncle, 3 of the 7 children were affected by a syndrome of malabsorption with various clinical symptoms. Diarrhea appeared in 2 of the children at birth, and in the third child at six months. The diarrhea led to failure-to-thrive, muscular wasting and abdominal swelling. However, the children improved spontaneously over the years. During childhood all 3 had manifest steatorrhea. Serum cholesterol was between 39 and 100 mg/dl, while triglycerides were normal to high. Reevaluation during the past year revealed areflexia, deficiency of vitamins A and E and of apoproteins A and B, and prolonged PT time in 2 of the children. Electron and light microscopy of small intestinal biopsies revealed vacuoles in the enterocytes. Electrophysiological tests revealed major disturbances in sensory conduction and brain-stem function. These cases differ from those described in the literature. Although in hypobetalipoproteinemia, 1 of the parents would be expected to be heterozygous and have low serum levels of APO B, in this family the parents had normal levels. Their children had low levels of serum APO A, while in patients with hypobetalipoproteinemia the levels are normal. There is a report of a case of deficiencies of both apolipoproteins, but the patient was asymptomatic, had chylomicronemia after a prolonged fast, and lower cholesterol levels than our patients. 8 other cases of apolipoprotein deficiency have been reported with biochemical characteristics similar to those of our patients, but with retention of chylomicrons in the small intestine.

Apoproteins↗

Localization of the X inactivation centre on the human X chromosome in Xq13.

X-chromosome inactivation results in the strictly cis-limited inactivation of many but not all genes on one of the two X chromosomes during early development in somatic cells of mammalian females. One feature of virtually all models of X inactivation is the existence of an X-inactivation centre (XIC) required in cis for inactivation to occur. This concept predicts that all structurally abnormal X chromosomes capable of being inactivated have in common a defineable region of the X chromosome. Here we report an analysis of several such rearranged human X chromosomes and define a minimal region of overlap. The results are consistent with models invoking a single XIC and provide a molecular foothold for cloning and analysing the XIC region. One of the markers that defines this region is the XIST gene, which is expressed specifically from inactive, but not active, X chromosomes. The localization of the XIST gene to the XIC region on the human X chromosome implicates XIST in some aspect of X inactivation.

Chromosome Mapping↗

Codon 618 variant of Alzheimer amyloid gene associated with inherited cerebral hemorrhage.

Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D) is an autosomal dominant form of severe cerebrovascular amyloid angiopathy causing recurrent strokes during the fifth and sixth decades of life. The major constituent of the amyloid deposits in HCHWA-D is the amyloid beta-protein (A beta), also found in Alzheimer's disease. A point mutation in the DNA sequence encoding A beta has been found in 2 unrelated patients with HCHWA-D, and an assay detecting the single base change was developed for diagnostic purposes. We describe the detection of the point mutation in a patient living in the United States, suffering from recurring cerebral hemorrhages, who only recently was diagnosed with HCHWA-D. In addition, we tested a number of family members, and found the mutation in 2 additional individuals, one of them too young to exhibit clinical manifestations. This study combined with the study of two other families in Holland indicates that the codon 618 variant in the amyloid precursor protein gene segregates with HCHWA-D.

Aged↗

Cytomegalovirus IgG and IgA serum antibodies in a study of HIV infection and HIV related diseases in homosexual men.

The significance of serum IgG and IgA antibodies to cytomegalovirus (CMV) at various stages of human immune deficiency virus (HIV) infection was studied in 175 homosexual men. Sera were obtained from 123 HIV seropositives [41 asymptomatic, 29 with lymphadenopathy associated syndrome (LAS), 22 with AIDS related complex (ARC), and 31 AIDS patients], 17 HIV seroconverters, and 35 HIV asymptomatic seronegatives. The sera were tested blindly for CMV IgA and IgG antibodies using the immunoperoxidase assay (IPA) and CMV infected human embryo cells. Cross-sectional analysis of CMV IgG antibodies at a titer of greater than or equal to 20 showed 87% and 100% prevalence in the HIV seronegative groups and in the HIV seropositive groups, respectively (P less than 0.05). CMV IgG antibodies at a titer of greater than or equal to 80 were present in significantly higher proportions among the HIV seropositive subjects of the various groups as compared with the HIV seronegative homosexual men. However, in the HIV seronegatives who later seroconverted to HIV, a significantly higher prevalence of CMV antibodies (35%) was detected before HIV seroconversion, as compared with the persistently HIV seronegative subjects (14.3%) (P less than 0.05). The HIV seronegatives pre-HIV seroconversion also exhibited a significantly higher geometric mean titer (GMT) of CMV IgG antibodies (62.17 +/- 0.64) as compared with the persistently HIV seronegatives (34.0 +/- 0.6) (P = 0.03). Significantly higher GMTs of CMV IgG antibodies were detected in all the HIV seropositive groups as compared with the persistently HIV seronegative group. CMV IgG antibodies were not detected in the HIV seronegative subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of clentiazem on lipid profile, lipoprotein composition and aortic fatty streaks in cholesterol-fed rabbits.

Numerous experimental studies have reported that common antihypertensive drugs such as diuretics, beta-blockers, and methyldopa have adverse effects on plasma lipids and lipoproteins. The present study was designed to define the effect of clentiazem (10 mg/kg/day) an antihypertensive drug, on hyperlipidemia in rabbits on a cholesterol-rich diet (1%) for 12 weeks. Compared with controls, clentiazem treated rabbits had lower plasma concentrations of triglycerides (55%), total cholesterol (24%), free cholesterol (27%), esterified cholesterol (23%) and phospholipids (24%). The decrease in cholesterol was accounted for by a reduction of VLDL-cholesterol (13%), IDL-cholesterol (24%) and primarily LDL-cholesterol (45%). Neither HDL-cholesterol nor chemical composition of VLDL, IDL, LDL and HDL was altered. When the aortic atherosclerotic involvement was evaluated by computerized planimetry, a 24% reduction of lesions was noted in clentiazem treated animals (P less than 0.05). Similarly, cholesterol content extracted from aortic wall was decreased. Our data therefore demonstrated that clentiazem is a potential antiatherosclerotic agent capable of decreasing plasma lipids and atherogenic lipoproteins as well as aortic fatty streaks.

Animals↗

Metabolic fate of chylomicrons obtained from rats maintained on diets varying in fatty acid composition.

The importance of the fatty acid component in the metabolism of chylomicrons was demonstrated by feeding diets varying in fatty acid composition which resulted in chylomicrons of different sizes. On a diet rich in polyunsaturated fatty acids (PUFA) from safflower oil, chylomicrons of diameter 1853 +/- 192 A were harvested from the mesenteric lymph, whereas on coconut oil and medium-chain triglyceride diets the chylomicron size was 1403 +/- 83 and 604 +/- 40 A, respectively. When the isolated chylomicrons were injected into recipient rats maintained on a regular diet, their half-life (t1/2) decreased from 5.4 +/- 0.4 to 1.8 +/- 0.3 min with the increase in particle size. No significant difference in the apolipoprotein profile of chylomicrons of various sizes was noted, indicating that alterations of chylomicron removal are not related to apolipoprotein composition. Rats maintained on PUFA diets showed a marked increase in their adipose tissue lipoprotein lipase activity. The fast removal of large chylomicrons and increased tissue lipoprotein lipase activity, together with suppression of hepatic lipogenesis on this diet, apparently explains the low plasma triglyceride level in rats maintained on diets rich in PUFAs.

Animals↗

["Ex situ-in vivo" surgery of the liver: a new technique in liver surgery. Principles and preliminary results].

Major liver resections with complex vascular reconstruction require ischemia lasting from 2 h 30 to 5 h thus exceeding hepatic tolerance to warm ischemia. We describe a new technique of "ex situ-in vivo" liver surgery with prolonged ischemia with an intact hepatic pedicle. The surgical procedure encompasses complete mobilization of the liver and inferior vena cava, inferior mesenteric and femoral to axillary vein bypass, complete vascular exclusion of the liver, cold perfusion (U. W. solution), section of the hepatic veins allowing exteriorization of the liver ("ex situ") which remains connected by the hepatic pedicle ("in vivo"). The liver is placed on a heat exchanger at 4 degrees C. This procedure was performed in three patients: one each with hepatocellular carcinoma, huge metastasis of colorectal carcinoma and a "diffuse" hemangioma. Duration of ischemia was 225, 205, and 230 min respectively. The postoperative course was uneventful in all 3 cases and patients are alive at 15, 12, and 6 months. As it improves resecability rate of liver tumors and provides radical margins of resection, this procedure may be a beneficial alternative to liver transplantation for which poor results in cancer therapy with a high rate of recurrence are mainly due to immunosuppression.

Carcinoma, Hepatocellular↗

DNA diagnosis for hereditary cerebral hemorrhage with amyloidosis (Dutch type)

Hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D) is tightly linked to the Alzheimer amyloid precursor protein gene on chromosome 21, which codes for the amyloid beta-protein. A point mutation detected at position 1852 of the amyloid precursor protein gene in four HCHWA-D patients was hypothesized to be the basic defect. This study proves that 22 HCHWA-D patients from three pedigrees all carry this point mutation, whereas the mutation is absent in escapees from the HCHWA-D families as well as in randomly selected Dutch individuals. A mutation-specific oligonucleotide is now available for the confirmation of the HCHWA-D diagnosis. Therefore, presymptomatic testing and prenatal evaluation of individuals at risk in the HCHWA-D families is now feasible.

Aged↗

Dietary-induced hyperlipidemia and renal function in the uremic rat.

Rats made uremic by 2-stage 5/6 nephrectomy and sham-operated control animals were fed either a normal laboratory chow, a high-sucrose (60%) or a high-fat (10% cholesterol; 20% olive oil) diet, all containing 21% protein and identical amounts of electrolytes, vitamins and trace elements. Serum creatinine levels remained unchanged in the control animals but rose in the 5/6 nephrectomised uremic animals by a factor of 2.7 from a mean of 0.44 +/- 0.05 mg/dl to 1.20 +/- 0.11 mg/dl at 8 weeks, without differences between the dietary groups. During 8 weeks of dietary regimen the high-sucrose and high-fat diets induced significant hypertriglyceridemia, generally similar in control and uremic rats. The uremic animals on a high-sucrose and high-fat diet had the most pronounced rise in serum triglycerides, 331.5 +/- 89.0 and 298.0 +/- 45.0 mg/dl, respectively (control: 159.9 +/- 14.0 mg/dl). After 4 and 8 weeks, only the animals on the high-fat diet had significant hypercholesterolemia, most pronounced in the uremic animals (356 +/- 56.3 mg/dl; control: 71.6 +/- 12.9 mg/dl). The animals in the latter group also had significant proteinuria and renal histologic abnormalities consisting of xanthoma-like glomerular lesions, infiltrates and fibrosis not seen in the other groups of animals. These data indicate that dietary-induced hyperlipidemia of short duration causes or aggravates renal damage in the rat with mild-moderate uremia, induced by ablation.

Animals↗

Mutation in gelsolin gene in Finnish hereditary amyloidosis.

Familial amyloidosis, Finnish type (FAF), is an autosomal dominant form of familial amyloid polyneuropathy. The novel amyloid fibril protein found in these patients is a degradation fragment of gelsolin, an actin-binding protein. We found a mutation (adenine for guanine) at nucleotide 654 of the gelsolin gene in genomic DNA isolated from five FAF patients. This site is polymorphic since the normal allele was also present in all the patients tested. This mutation was not found in two unaffected family members and 11 normal controls. The A for G transition causes an amino acid substitution (asparagine for aspartic acid) that was found at position 15 of the amyloid protein. The mutation and consequent amino acid substitution may lead to the development of FAF.

Amino Acid Sequence↗