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Y Levy

Publications and source records attributed to Y Levy.

At least 181 records · Page 10Linked to original sources

Atherosclerosis in LDL-receptor knockout mice is accelerated by immunization with anticardiolipin antibodies.

Atherosclerosis is a process initiated by accumulation of macrophages in distinct areas of endothelial cell damage and uptake of large amounts of lipids. Recently, it has been shown that the immune system plays an active part in the progression of the atherosclerotic plaque although its precise role has not yet been elucidated. Anticardiolipin antibodies (aCL) are generally found in the sera of patients with the antiphospholipid syndrome (APS) and are associated with a prothrombotic state. Several authors have demonstrated that aCL can activate platelets and endothelial cells as well as increase oxidized low density lipoprotein (LDL) uptake by macrophages. In the present study we sought to assess the effect of immunization with aCL (Ab1, leading to the production of mouse aCL-Ab3) on the progression of atherosclerosis. Two groups of 8-weeks old female LDL-receptor knockout mice (n = 13 per group) were immunized with IgG purified from the serum of an APS patient or with normal human IgG, respectively. The aCL immunized mice developed high titres of 'self' aCL (detected using the standard aCL ELISA) as compared with the normal human IgG immunized mice, whereas no differences were noted between both study groups with respect to the serum lipid levels. The extent of fatty streak formation was significantly higher in the aCL immunized mice in comparison with the human IgG injected mice (mean aortic lesion size of 5308 +/- 471 microns2 vs 1027 +/- 184 microns2, respectively, P < 0.01). The immunohistochemical analysis of the atherosclerotic plaques from both mouse groups did not display differences in cellular composition. The results of the study show that mouse aCL induced by immunization with human aCL from an APS patient enhance atherogenesis in LDL-RKO mice and imply that these antibodies may play a role in atherosclerosis development in patients with the APS.

Animals↗

Aspirin for prevention of myocardial infarction. A double-edged sword.

BACKGROUND: The use of low dose aspirin is associated with upper gastrointestinal bleeding, especially in the elderly. Anemia is one of the risk factors of acute myocardial infarction especially in patients with ischemic heart disease. METHODS AND RESULTS: We present a series of fifteen patients treated with low dose aspirin for secondary prevention of ischemic heart disease who had upper GI bleeding and were admitted to our hospital because of unstable angina or myocardial infarction. Nine patients had acute myocardial infarction and six patients had unstable angina. The mean age of the patient was 72 +/- 9 years. Only two patients had a previous history of duodenal ulcer before their admission. The duration of aspirin therapy ranged from a few days to more than a year. Weakness, abdominal pain and melena were present in most of the patients between 2-7 days before the appearance of chest pain, and syncope was the chief complaint in 5 patients. CONCLUSIONS: We conclude that aspirin which is given to patients in order to prevent myocardial infarction might cause myocardial infarction as a sequella of upper gastrointestinal bleeding. Lack of patient education was the primary cause of the delayed diagnosis of this complication. Instruction of patients treated by aspirin to seek medical advise because of symptoms of gastrointestinal bleeding could prevent acute myocardial infarction in patients treated by aspirin who have upper gastrointestinal bleeding.

Aged↗

Analysis of different glycosylation states in IgG subclasses.

Altered IgG glycosylation affects certain immunological activities of human IgG. Enzyme-linked lectin assays (ELLA) were developed for detecting the glycosylation on IgG and its individual subclasses in sera from healthy controls. Biotinylated Sambucus nigra, Ricinus communis agglutinin I and Bandeiraea simplicifolia II were used to detect the terminal sialic acid (SA), galactose (Gal) and N-acetylglucosamine (GlcNAc) sugar residues, respectively on the captured IgG. A mild oxidation step of the anti-IgG-coated plates obviated background reaction with the lectins. Terminal glycosylation varied significantly with age. The old age group (> 65 years) had less SA in IgG1, and IgG2, when compared to young (0-19 years) and adult (20-39 years) groups, respectively. Also the old age group had less Gal in IgG2, IgG3 and IgG4 subclasses compared to the adult group, and to the young group in the case of IgG3. This ELLA system may be a valuable tool in the detection of glycosylation disorders in patients' sera.

Adult↗

All-trans-retinoic acid in POEMS syndrome. Therapeutic effect associated with decreased circulating levels of proinflammatory cytokines.

Chronically elevated serum levels of proinflammatory cytokines is a feature of the syndrome known as POEMS (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal [M] protein, skin changes). A patient had a POEMS syndrome with thrombocytosis and biclonal gammopathy and was treated as follows: all-trans-retinoic acid (tretinoin) at 90 mg/day for 50 days, no treatment for 70 days, readministration of tretinoin at 75 mg/day for 180 days. Focal bone lesion irradiation was performed from day 26 to day 50. Serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), and IL-1 beta normalized within 7 days after the first administration of tretinoin, transiently increased at the time of radiotherapy, increased again after withdrawal of the tretinoin, and decreased again after its reintroduction. The platelet count and gammopathy paralleled the changes in the cytokine levels. This study documents in vivo the ability of all-trans-retinoic acid to down-regulate the release of IL-6, IL-1 beta, and TNF alpha, and illustrates its potential as a therapeutic agent in conditions associated with chronic overproduction of proinflammatory cytokines.

Cytokines↗

Modularity of language reconsidered.

This paper focuses on claims for the modularity of language that have been voiced within the field of cognitive developmental disorders. It will be argued that, whereas there is sound empirical support for "little" modularity, i.e., the internal modularity of the grammar, the cases that have been brought up in the literature do not, in fact, provide support for "Big" Modularity, i.e., the Modularity of the language faculty. The cases discussed are children with William's Syndrome and the retarded individuals studied by Cromer (1993), Curtiss (1979, 1988), Rondal (1993), Smith and Tsimpli (1995), and Yamada (1990). Rather then making the case for Modularity. it is suggested that these individuals' linguistic performance can best be described in terms of uniquely preserved accessing privileges for language which enable them to reach levels of performance that they cannot reach through other modalities.

Brain↗

Severe Blastocystis hominis in an elderly man.

We describe a unique case of severe Blastocystis hominis infection in an elderly man with severe dehydration, marked leukocytosis and hypoalbuminaemia after antibiotic treatment for right pneumonia. The patient recovered after treatment with metronidazole. This case presentation demonstrates the ability of B. hominis to induce severe gastrointestinal manifestations and general deterioration, particularly in light of the controversy surrounding its possible potential pathogenicity. We believe, therefore that aggressive treatment with metronidazole should be instituted, following demonstration of the parasite in the stools, if diarrhoea is protracted, since it may well be attributed to Blastocystis infection.

Aged↗

The effects of early and late administration of M-20 derived interleukin-1 inhibitor on experimental systemic lupus erythematosus.

M-20 interleukin-1 inhibitor is produced by a myelomonocytic cell line. The effects of this molecule, mediated via IL-1 inhibition, include decreased proliferative responses of mouse thymocytes, human T-cells and fibroblasts and reduction in parameters of acute inflammation. Previously, we have demonstrated the emergence of a disease resembling systemic lupus erythematosus (SLE) in naive mice immunized with anti-DNA antibodies carrying different pathogenic idiotypes. The disease was manifested by increased titers of various mouse antibodies, concomitant with the appearance of elevated erythrocyte sedimentation rate (ESR), proteinuria and leukopenia. We have applied this model of experimental SLE (immunized with MIV-7, a human monoclonal antibody) to evaluate the influence of M-20 IL-1 inhibitor, administered at different stages (2 weeks before, 1 month and 3 months following immunization) for a period of 2 weeks, on the findings of the disease in mice. It was shown that M-20 IL-1 inhibitor given 2 weeks prior to the immunization resulted in suppression of the disease induction as documented by lower antibody titer level (30%-50% in the immunized mice as compared with controls). Furthermore, reduced autoantibody levels were accompanied by other beneficial findings consisting of lower ESR, less severe proteinuria and elevated leukocyte counts. No beneficial effects of M-20 IL-1 inhibitor were observed when the agent was administered 1 or 3 months following immunization. We conclude that M-20 IL-1 inhibitor has a favorable effect on experimental SLE in mice, provided it is administered before induction of the disease.

Animals↗

Retinoic acid modulates the in vivo and in vitro growth of IL-6 autocrine human myeloma cell lines via induction of apoptosis.

We previously showed that IL-6 is an autocrine growth factor for two human myeloma cell lines, RPMI 8226 and U266. We investigated here the in vitro and in vivo effects of all-trans retinoic acid (RA) on the growth and survival of these two cell lines. RA induced a dramatic dose- and time-dependent inhibition of the proliferation of both cell lines. This inhibition was correlated with a down-modulation of the cell surface expression of the IL-6 binding chain (gp80) and the transducing chain (gp130) of the IL-6 receptor (IL-6R). Long-term culture experiments showed that down-modulation of gp80 expression was complete at days 15 and 30 in the presence of 10(-5) and 10(-7) mol/l of RA, respectively. Gp 130 expression was greatly decreased, albeit still detectable, in similar culture conditions. RA-mediated interruption of the IL-6 autocrine loop was associated with a decrease of bcl-2 oncoprotein expression and apoptosis of the myeloma cells which was RA concentration- and time-dependent. The in vivo relevance of the effects of RA was studied on tumours which developed in nude mice inoculated with a subclone of RPMI 8226. Whereas tumours grew in all control mice, 40% of tumours regressed within 20 days in RA-treated mice. Cells from regressing tumours featured characteristics of apoptosis and exhibited low gp80 and gp130 expression. Our study indicate that long-term RA treatment interferes in vivo and in vitro with IL-6 autocrine growth of myeloma cell lines, leading to apoptosis.

Animals↗

Co-regulation of apo A-I, apo C-III and apo A-IV gene expression in human intestinal biopsies.

The apo A-I gene is expressed in the liver and small intestine. In order to study the role of human intestinal transcription of the apo A-I gene in determining plasma high-density lipoprotein, (HDL)-cholesterol and apo lipoprotein (apo) A-I concentrations, the authors measured the relative mRNA levels of apo A-I in human intestinal biopsies. Biopsies were taken from 50 fasting subjects (25 males and 25 females). At the same time blood was taken for lipid and lipoprotein analysis. Plasma HDL-cholesterol correlated linearly with plasma apo A-I protein. No correlation could be demonstrated between intestinal apo A-I mRNA and plasma apo A-I or HDL-cholesterol levels. The apo A-I gene resides in an apolipoprotein cluster with the apo C-III and apo A-IV genes. To assess whether there is a coordinated expression of this locus, Northern blot analysis of intestinal RNA was performed. The authors have demonstrated that under fasting conditions mRNA levels of apo A-I, C-III and A-IV are co-regulated in the intestine.

Adult↗

Sarcoidosis mimicking toxoplasmosis with severe hypercalcaemia and normal 1,25-dihydroxy vitamin D.

We report a case of a female patient with sarcoidosis who presented with a generalized lymphadenopathy and a strong IgG serological test of toxoplasmosis. Progressive lymphadenopathy with a rising plasma calcium (up to 15 mg dL-1) with a normal plasma 1,25-dihydroxy vitamin D concentration occurred later. Corticosteroid therapy resulted in prompt clinical and biochemical responses with normalization of plasma calcium and a significant reduction in 1,25-dihydroxy vitamin D concentration. This is an exceptional presentation of sarcoidosis with severe hypercalcaemia and normal vitamin D metabolites.

Adult↗

Bioavailability of a natural isomer mixture compared with synthetic all-trans beta-carotene in human serum.

The unicellular alga Dunaliella bardawil was shown previously to contain very high concentrations of beta-carotene composed of about equal amounts of the all-trans and 9-cis isomers, which differ in their physicochemical features and antioxidative activity. The uptake of alpha- and beta-carotenes, oxycarotenoids, and other lipophilic substances from a basal diet supplemented with synthetic beta-carotene or dry D. bardawil power was studied in humans. Subjects were given a basal diet supplemented daily with 40 mg beta-carotene, synthetic or natural, for a relatively short period of 14 d. Serum analyses at the end of this period detected mainly oxycarotenoids, and to a lesser extent all-trans beta-carotene and alpha-carotene, but not 9-cis beta-carotene. Retinol was increased by the all-trans beta-carotene diet. A high amount of oxidized dienic, lipophilic polar products was exhibited in HPLC predominantly in sera from the placebo and synthetic all-trans beta-carotene groups by strong, short ultraviolet absorbance peaks of 232 nm. The preferential serum absorption of all-trans beta-carotene over 9-cis beta-carotene, in parallel with the appearance of a high concentration of oxidized dienic products with supplementation of the basal diet with all-trans beta-carotene compared with the low concentration of serum-oxidized dienic products with supplementation with a natural beta-carotene source, suggests that 9-cis beta-carotene acts as an in vivo lipophilic antioxidant more efficiently than does all-trans beta-carotene.

Adult↗

Consumption of eggs with meals increases the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation.

Consumption of eggs for a long period was shown to result in hypercholesterolemia and is generally restricted for this reason. In the present study we analyzed the effect of eggs consumption for 3 weeks on lipoprotein atherogenicity. Consumption of 2 eggs per day with the meals, for 3 weeks resulted in a minor elevation in plasma glucose and urea concentrations. Plasma cholesterol concentration increased by 11% (p < 0.05) as a result of increased plasma low-density lipoprotein (LDL) cholesterol levels. Plasma triglycerides decreased by 13% (p < 0.01), but there were no significant alterations in plasma apolipoproteins A-I or B-100 concentrations. Plasma high-density lipoprotein (HDL) cholesterol decreased by 11% (p < 0.05). There was a 13% reduction, though not significant, in the cholesterol efflux from J-774 A.1 macrophages by HDL that was derived after eggs consumption in comparison to HDL that was obtained at baseline. The susceptibility of plasma [using 100 mM of 2,2' azobis 2-amidinopropane (AAPH)] as well as that of LDL (using 10 microM of copper ions) to lipid peroxidation was increased by 42% and 34%, respectively, as measured by the thiobarbituric acid reactive substance (TBARS) assay (p < 0.01). Kinetic analysis of LDL oxidation by copper ions revealed a 37% reduction in the lag time required for the initiation of LDL oxidation after 3 weeks of eggs consumption. The total plasma fatty acids concentration increased from 2.2 +/- 0.5 to 3.2 +/- 0.6 mg/ml. The plasma antioxidants, vitamin E and carotenoids were not significantly affected by eggs consumption. We conclude that eggs consumption, in addition to its hypercholesterolemic effect, increases plasma and LDL oxidizability, a phenomenon which was shown to enhance the progression of atherosclerosis. The atherogenic properties may contribute to the accelerated atherosclerosis prevalent in populations with high cholesterol intake.

Adult↗

Modulation of experimental systemic lupus erythematosus with linomide.

OBJECTIVE: The objective of this study was to assess the beneficial effects of an early administration of low dose linomide, a new immunomodulator, in an animal model of experimental systemic lupus erythematosus (SLE). METHODS: Experimental SLE was induced in naive BALB/c mice, by immunization with anti-DNA mAb (MIV-7). Control Mice immunized with irrelevant human IgM served as controls. The immunized mice were treated with linomide (0.1 mg/ml in the drinking water), four weeks prior to the first immunization, at an early stage of the disease induction (one month after boost injection), or at a later stage (3 months following boost immunization). The treatment duration was 3 months in all schedules. The follow-up studies continued for 8 weeks after discontinuation of the treatment. The presence in the serum of autoantibodies against ssDNA, dsDNA histones, phospholipids and an irrelevant autoantigen-pyruvate dehydrogenase, was determined by enzyme-linked immunosorbent assay (ELISA). The clinical parameters assessed included erythrocyte sedimentation rate, peripheral blood cell counts and proteinuria. RESULTS: There was a 50-64% decrease in autoantibody levels in the sera of mice immunized with anti-DNA (MIV-7) mAb at the early stage of experimental SLE in mice which received linomide for a period of 3 months. No effect of linomide was noted in mice which received the drug during the later stages of experimental SLE when the disease was fully developed. Linomide had a preventive effect on the induction of experimental SLE in naive mice, when the treatment was initiated before the induction of the disease. This effect was abolished following cessation of the treatment. CONCLUSIONS: Linomide proved to be effective at the early stages of induction of the experimental SLE. However, the autoantibody levels rose following discontinuation of the therapy.

Adjuvants, Immunologic↗