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Biomedical subjects

S Levy

Publications and source records attributed to S Levy.

At least 73 records · Page 4Linked to original sources
PubMed2000

[Tolerance and efficacy of carvedilol prescription in patients with mild to moderated chronic heart failure].

The current treatment for heart failure, i.e., carvedilol administration, has brought about a significant reduction in cardiovascular morbidity and mortality. The European Cardiology Association task-force has recently recalled that the treatment for heart failure should be considered differently according to the regions within Europe. However, most studies have involved North American or Australasian subjects. The results of these studies have shown that carvedilol improves the symptomatic status of patients with mild to moderate chronic heart failure, but their extrapolation to the situation in Europe is questionable. In the present study, the authors have reported on the use of this beta-blocker over a 6-month period in 48 European subjects (an older patient population, and more frequently given digitalis treatment) with mild to moderate stage II and III chronic heart failure (mean NYHA functional stage = 2.75 +/- 0.2; mean left ventricular ejection fraction = 32.4 +/- 3.4). Six patients (12.5%) were obliged to withdraw from the study due to adverse reactions to carvedilol, i.e., 2 subjects during the test-dose (4.2%) and 4 others who were subsequently unable to withstand the progressive stepping up of drug dosage (8.3%). In the remaining 42 patients, the mean NYHA scores dropped significantly from 2.75 +/- 0.2 to 1.8 +/- 0.1 (p < 0.05) at the end of the study period, indicating an increase in symptomatic improvement with a favorable hemodynamic tolerance profile, even in cases of combined therapy with digitalis. This study confirms the positive action of carvedilol on functional symptomatology in southern European patients presenting with mild to moderate chronic heart failure. However, it should be emphasized that this beta-blocker should only be administered under strict and specialized medical surveillance as its effect of significantly slowing down the heart rate could also result in cardiac insufficiency.

Adrenergic beta-Antagonists↗
PubMed1999

Rapid production of specific vaccines for lymphoma by expression of the tumor-derived single-chain Fv epitopes in tobacco plants.

Rapid production of protein-based tumor-specific vaccines for the treatment of malignancies is possible with the plant-based transient expression system described here. We created a modified tobamoviral vector that encodes the idiotype-specific single-chain Fv fragment (scFv) of the immunoglobulin from the 38C13 mouse B cell lymphoma. Infected Nicotiana benthamiana plants contain high levels of secreted scFv protein in the extracellular compartment. This material reacts with an anti-idiotype antibody by Western blotting, ELISA, and affinity chromatography, suggesting that the plant-produced 38C13 scFv protein is properly folded in solution. Mice vaccinated with the affinity-purified 38C13 scFv generate >10 micrograms/ml anti-idiotype immunoglobulins. These mice were protected from challenge by a lethal dose of the syngeneic 38C13 tumor, similar to mice immunized with the native 38C13 IgM-keyhole limpet hemocyanin conjugate vaccine. This rapid production system for generating tumor-specific protein vaccines may provide a viable strategy for the treatment of non-Hodgkin's lymphoma.

Amino Acid Sequence↗
PubMed1999

Process mapping in screening mammography.

Successful screening mammography programs aim to screen large numbers of women efficiently and inexpensively. Development of an effective screening mammography program requires skilled personnel, solid infrastructure, and a robust computer system. A group of physicians, technologists, computer support personnel, and administrators carefully analyzed a growing screening mammography program as a series of steps, starting with the request for the examination and ending with the receipt of a hard-copy consultation. The analysis involved a detailed examination of every step and every possible outcome in the screening process. The information gained through process mapping may be used for identification of systemic and personnel problems, allocation of resources, modification of workplace architecture, and design of computer networks. Process mapping is helpful for those involved in designing and improving screening mammography programs. Viewing a process (i.e., obtaining a screening mammogram) as a series of steps may allow for the identification of inefficient components that may limit growth.

Adult↗
PubMed1999

Adenosine plasma concentration in pulmonary hypertension.

OBJECTIVE: In this study, we sought to appreciate the role of adenosine in the regulation of pulmonary vascular tone, especially in the case of clinical pulmonary hypertension, by investigating the relationship between endogenous plasma adenosine levels and pulmonary artery vasoconstriction. METHODS: Adenosine plasma concentrations, were measured simultaneously in the distal right pulmonary artery and in the femoral artery, both at steady state (room air) and during pure oxygen inhalation. Three clinical situations were considered: (1) normal hemodynamics [7 control subjects, mean pulmonary artery pressure (MPAP) = 18.5 +/- 1 mm Hg], (2) moderate pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD), (8 patients, MPAP = 31 +/- 3 mm Hg), (3) severe primary pulmonary hypertension (PPH), (8 patients, MPAP = 70 +/- 5 mm Hg). RESULTS: In every instance, adenosine evaluated by HPLC was higher in the pulmonary than in the systemic circulation. For room air, adenosine plasma concentrations were significantly lower in COPD (0.49 +/- 0.16 mumol l-1) and PPH patients (0.45 +/- 0.14 mumol l-1) than in controls (1.26 +/- 0.12 mumol l-1). During O2 administration, adenosine plasma concentrations all decreased but more so in COPD and PPH patients. The significant correlations between adenosine plasma concentrations and both pulmonary vascular resistance and PvO2, in controls, were not found in COPD or PPH patients. CONCLUSION: The adenosine plasma concentrations in the pulmonary circulation of PPH and COPD patients are low, and may contribute to pulmonary artery hypertension.

Adenosine↗
PubMed1999

Frequent factor II G20210A mutation in idiopathic portal vein thrombosis.

BACKGROUND & AIMS: Despite extensive investigations of portal vein thrombosis, no underlying cause is identifiable in up to 30% of patients. A recently described mutation of the prothrombin gene at nucleotide position 20210 is associated with history of venous thrombosis and was assessed in this study. METHODS: We compared the frequency of factor II G20210A and factor V G1691A (factor V Leiden) mutations in 10 patients with idiopathic portal vein thrombosis, 10 patients with nonidiopathic portal vein thrombosis, 60 patients with deep vein thrombosis of the legs, and 42 control subjects. RESULTS: The frequency of factor II G20210A mutation was increased in patients with idiopathic portal vein thrombosis (40.0%; confidence interval, 3.1%-76.9%) compared with controls (4.8%; confidence interval, 0%-11.5%) or patients with nonidiopathic portal vein thrombosis or deep vein thrombosis (P = 0.0001). In contrast, the frequency of the factor V G1691A mutation was similar in subjects with portal vein thrombosis and in controls but was increased in patients with deep vein thrombosis (P = 0.0001). CONCLUSIONS: The factor II G20210A mutation is frequent in patients with idiopathic portal vein thrombosis and should therefore be assessed under this circumstance.

Adult↗
PubMed1999

Segment-specific changes with age in the expression of junctional proteins and the permeability of the blood-epididymis barrier in rats.

In aging Brown Norway rats, there is a striking increase in the number of halo cells in the epididymis; this reflects an activation of the immune system. As the blood-epididymis barrier should protect from immunological attack, we hypothesized that there would be changes in the structure and function of this barrier with age. To test this hypothesis, we assessed the immunocytochemical localization of occludin, ZO-1, and E-cadherin, as well as the lanthanum nitrate permeability of the blood-epididymis barrier, in the epididymides of Brown Norway rats aged 3, 18, and 24 mo. In the initial segment, occludin, ZO-1, and E-cadherin immunostaining was observed at the apico-lateral junction between principal cells in the 3-mo-old animals; with increasing age, occludin and ZO-1 reactivity decreased, while E-cadherin staining increased along the lateral membrane between principal cells. In the caput, corpus, and cauda epididymidis, occludin, ZO-1, and E-cadherin immunostaining showed segment-specific and age-dependent differences in their staining patterns. The most dramatic changes were seen in the corpus epididymidis with age; the intense E-cadherin cytoplasmic staining that was observed at 3 mo was absent by 24 mo, and no occludin or ZO-1 reactivity was observed in older animals. The greatest penetration of lanthanum nitrate across the blood-epididymis barrier and in the lumen was seen in the aging corpus epididymidis, while there was no barrier permeability in the initial segment or cauda epididymidis of the aged animals. Taken together, these data indicate that there are segment-specific decreases in the structural and functional integrity of the blood-epididymis barrier with age, most notably in the corpus epididymidis.

Aging↗
PubMed1999

Hemodynamic response to oxygen administration in chronic heart failure: role of chemoreflexes.

The aim of this study was to assess whether arterial chemoreceptors are activated in chronic heart failure and to appreciate whether this activation is related to the degree of cardiac dysfunction. We examined whether administration of pure oxygen for 30 min to 35 patients with chronic heart failure was followed by hemodynamic modifications that would suggest a negative feedback (inactivation) of such chemoregulation. A decrease in heart rate and cardiac output was observed in all patients. The decrease in cardiac output and stroke volume was inversely correlated to the left ventricular ejection fraction. We observed that the lower the left ventricular ejection fraction, the smaller the decrease in heart rate and the greater the increase in systemic vascular resistance. The variation of stroke volume was related to the variation of systemic vascular resistance. In 12 patients, keeping heart rate constant during oxygen inhalation by adequate right atrial pacing prevented the decrease of cardiac output. These results suggest that chemoregulation remains generally effective in chronic heart failure: increase in Pao2 resulted in a reduction of cardiac output mainly related to the decrease of heart rate. However, when the left ventricular function is very poor, the central chemomediated regulation is impaired, and the direct peripheral effect of oxygen on systemic circulation appears to play a leading part.

Aged↗
PubMed1999

Characterization of hepatitis C virus E2 glycoprotein interaction with a putative cellular receptor, CD81.

A truncated soluble form of the hepatitis C virus E2 glycoprotein, E2661, binds specifically to the surface of cells expressing human CD81 (hCD81) but not other members of the tetraspanin family (CD9, CD63, and CD151). No differences were noted between the level of E2661 binding to hCD81 expressed on the surface of rat RBL or KM3 cells compared to Daudi and Molt-4 cells, suggesting that additional human-cell-specific factors are not required for the primary interaction of E2 with the cell surface. E2 did not interact with African green monkey (AGM) CD81 on the surface of COS cells, which differs from the hCD81 sequence at four residues within the second extracellular region (EC2) (amino acids [aa] 163, 186, 188, and 196), suggesting that one or more of these residues defines the site of interaction with E2. Various recombinant forms of CD81 EC2 show differences in the ability to bind E2, suggesting that CD81 conformation is important for E2 recognition. Regions of E2 involved in the CD81 interaction were analyzed, and our data suggest that the binding site is of a conformational nature involving aa 480 to 493 and 544 to 551 within the E2 glycoprotein. Finally, we demonstrate that ligation of CD81 by E2661 induced aggregation of lymphoid cells and inhibited B-cell proliferation, demonstrating that E2 interaction with CD81 can modulate cell function.

Animals↗
PubMed1999

Functional analysis of cell surface-expressed hepatitis C virus E2 glycoprotein.

Hepatitis C virus (HCV) glycoproteins E1 and E2, when expressed in eukaryotic cells, are retained in the endoplasmic reticulum (ER). C-terminal truncation of E2 at residue 661 or 715 (position on the polyprotein) leads to secretion, consistent with deletion of a proposed hydrophobic transmembrane anchor sequence. We demonstrate cell surface expression of a chimeric glycoprotein consisting of E2 residues 384 to 661 fused to the transmembrane and cytoplasmic domains of influenza A virus hemagglutinin (HA), termed E2661-HATMCT. The E2661-HATMCT chimeric glycoprotein was able to bind a number of conformation-dependent monoclonal antibodies and a recombinant soluble form of CD81, suggesting that it was folded in a manner comparable to "native" E2. Furthermore, cell surface-expressed E2661-HATMCT demonstrated pH-dependent changes in antigen conformation, consistent with an acid-mediated fusion mechanism. However, E2661-HATMCT was unable to induce cell fusion of CD81-positive HEK cells after neutral- or low-pH treatment. We propose that a stretch of conserved, hydrophobic amino acids within the E1 glycoprotein, displaying similarities to flavivirus and paramyxovirus fusion peptides, may constitute the HCV fusion peptide. We demonstrate that influenza virus can incorporate E2661-HATMCT into particles and discuss experiments to address the relevance of the E2-CD81 interaction for HCV attachment and entry.

Animals↗
PubMed1998

Cytotoxic T cell responses to DNA vaccination: dependence on antigen presentation via class II MHC.

This study was designed to test whether cytotoxic T cell (CTL) responses to DNA vaccination are dependent upon MHC class II-restricted priming of CD4+ T cells. Because DNA vaccination may directly transfect dendritic cells, and dendritic cells may be capable of directly stimulating CD8+ T cell responses, such priming might be unnecessary. To test this hypothesis, C57BL/6 mice were immunized intramuscularly or intradermally with DNA encoding either whole OVA, a class I (Kb)-restricted peptide epitope of OVA (amino acids 257-264, SIINFEKL), or this class I-restricted epitope plus the adjacent class II (I-Ab)-restricted epitope of OVA (amino acids 265-280, TEWTSSNVMEERKIKV). Very low to negligible CTL responses were observed in mice vaccinated with the SIINFEKL construct, whereas mice vaccinated with the SIINFEKLTEWTSSNVMEERKIKV or with the complete OVA construct made equally robust CTL responses. These responses were sensitive to blocking by anti-CD8 mAb and were shown to be SIINFEKL-specific by using SIINFEKL peptide-pulsed EL-4 cells as targets. To ensure that the generation of these CTL responses was indeed dependent upon CD4+ T cell help, mice were depleted of either CD4+ or CD8+ cells before immunization. Depletion of CD4+ cells completely abrogated the CTL response to OVA DNA, as did depletion of CD8+ cells. Thus, we conclude that the CTL response to both intramuscular and intradermal DNA vaccination is highly dependent upon the generation of CD4+ T cell help via a class II MHC-dependent pathway. These results will be relevant for the construction of minimal-epitope vaccines for DNA immunization.

Amino Acid Sequence↗
PubMed1998

[Utilization of transcutaneous anesthetics during heart catheterization].

OBJECTIVES: Assess the efficacy of an anesthetic cream for cardiac catheterization. PATIENTS AND METHODS: Percutaneous anesthesia was studied in a series of 100 consecutive patients undergoing cardiac catheterization. The anesthesia was composed with an eutetic mixture of local anesthetics and applied precisely over the puncture area in a randomized controlled study. After admission, patients were randomized into two groups: 50 patients received lidocaine infiltration and 50 patients received associated cream and infiltration. Percutaneous anesthesia was to be applied 2 hours before entering the operating room. RESULTS: No complication developed with this cream combined with lidocaine infiltration. Serum concentration indicated very low levels which were very well tolerated. Patient comfort improved with the anesthetic cream-lidocaine infiltration association. CONCLUSION: The use of an anesthetic cream is safe and effective, especially combined with lidocaine infiltration during cardiac catheterization. Cost is high and the association might be reserved for special indications (obesity, children).

Aged↗
PubMed1998

Sequences and expression of six new members of the tetraspanin/TM4SF family.

Tetraspanins (or TM4SF) are expressed in a wide variety of species and regulate cell adhesion, migration, proliferation and differentiation. We have identified and sequenced six new members of the tetraspanin family, called Tspan-1-6, from human cDNA. Amino acid sequence analysis of the Tspans highlights conserved residues which may be critical to tetraspanin structure and function. The Tspans are differentially expressed in human tissues.

Amino Acid Sequence↗
PubMed1998

CD81 on B cells promotes interleukin 4 secretion and antibody production during T helper type 2 immune responses.

Mice lacking CD81 (TAPA-1), a widely expressed tetraspanin molecule, have impaired antibody responses to protein antigens. This defect is specific to antigens that preferentially stimulate a T helper 2 response (ovalbumin or keyhole limpet hemocyanin in alum) and is only seen with T cell-dependent antigens. Absence of CD81 on B cells is sufficient to cause the defect. Also, antigen-specific interleukin (IL) 4 production is greatly reduced in the spleen and lymph nodes of CD81-null mice compared with heterozygous littermates. Thus, expression of CD81 on B cells is critical for inducing optimal IL-4 and antibody production during T helper 2 responses. These findings suggest that CD81 may interact with a ligand on T cells to signal IL-4 production. By using a soluble form of CD81 as a probe, a putative ligand for CD81 was identified on a subset of B and T cells. Two possible models for the interaction of CD81 on B cells with a potential ligand on either B or T cells are proposed.

Animals↗
PubMed1998

Gene organization and chromosome location of the neural-specific RNA binding protein Elavl4.

We have isolated the gene that encodes the neural-specific RNA binding protein HuD in the mouse (Elavl4), and have mapped its location to the mid-distal region of chromosome 4, close to the neurological mutant clasper. The coding region of the Elavl4 gene covers approximately 44 kb; the first two RNA binding domains (RBDs) that are homologous to the two RBDs found in the Drosophila sex-lethal gene are each encoded in two exons, whereas the third RBD is encoded in a single exon. Elavl4 mRNAs are alternatively spliced in the region between RBDs 2 and 3 due to the variable use of two micro-exons, and RNase protection analysis indicates that two of four possible splice variants are the predominant isoforms expressed in the central nervous system. The high degree of sequence conservation between the Hu proteins suggests that the exon organization of all the Hu protein genes will be similar, if not identical, to the Elavl4 gene.

Aging↗
PubMed1998

Identification and functional analysis of hPRP17, the human homologue of the PRP17/CDC40 yeast gene involved in splicing and cell cycle control.

The PRP17 gene of the yeast Saccharomyces cerevisiae encodes a protein that participates in the second step of the splicing reaction. It was found recently that the yeast PRP17 gene is identical to the cell division cycle CDC40 gene. The PRP17/CDC40 gene codes for a protein with several copies of the WD repeat, a motif found in a large family of proteins that play important roles in signal transduction, cell cycle progression, splicing, transcription, and development. In this report, we describe the identification of human, nematode, and fission yeast homologues of the PRP17/CDC40 gene of S. cerevisiae. The newly identified proteins share homology with the budding yeast protein throughout their entire sequence, with the similarity being greatest in the C-terminal two thirds that includes the conserved WD repeats. We show that a yeast-human chimera, carrying the C-terminal two thirds of the hPRP17 protein, is able to complement the cell cycle and splicing defects of a yeast prp17 mutant. Moreover, the yeast and yeast-human chimeric proteins co-precipitate the intron-exon 2 lariat intermediate and the intron lariat product, providing evidence that these proteins are spliceosome-associated. These results show the functional conservation of the Prp17 proteins in evolution and suggest that the second step of splicing takes place by a similar mechanism throughout eukaryotes.

Animals↗
PubMed1998

Catastrophic worrying: personal inadequacy and a perseverative iterative style as features of the catastrophizing process.

This article describes 6 studies that have used a catastrophizing interview technique to investigate some of the characteristics of catastrophic worrying. The main findings were (a) worriers were willing to catastrophize both a positive aspect of their life and a new hypothetical worry significantly more than nonworriers, (b) worriers were more likely than nonworriers to rate catastrophizing steps for a new worry as containing information relevant to existing worries, (c) worriers displayed a general iterative style that was independent of the valency of the iterative task, and (d) worriers tended to couch their worries in terms of personal inadequacies, and personal inadequacy became a feature of their catastrophizing regardless of the worry topic. Worriers' tendency to couch worries and catastrophizing steps in terms of personal inadequacies and their perseverative iterative style are both important contributors to the unresolved catastrophic thought experienced by chronic worriers.

Adolescent↗