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Biomedical subjects

D Weill

Publications and source records attributed to D Weill.

At least 19 recordsLinked to original sources
PubMed1995

Monocyte modulation of endothelial leukocyte adhesion molecules.

Leukocyte adhesion to endothelium is dependent on expression of specialized molecules. Several of these molecules are upregulated by cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). We investigated the effect of medium conditioned by unstimulated (MCM) or stimulated monocytes and of recombinant cytokines on endothelial adhesion receptor expression. IL-1 beta, TNF-alpha, and MCM induced E-selectin similarly, whereas MCM induced VCAM-1 and ICAM-1 to a lesser extent than did TNF-alpha, and MCM induced VCAM-1 only weakly. The addition of pentoxifylline (10(-3) mol/L) to monocytes during MCM preparation blocked TNF-alpha production but not that of IL-1 beta or IL-6, and it reduced IL-1ra significantly (p < 0.05). When the MCM was devoid of TNF-alpha or when TNF-alpha was neutralized with a specific antibody, the action of MCM on E-selectin expression was significantly lower. Anti-IL-1 beta decreased the activity of MCM on endothelial E-selectin expression by about 50%. The effect of MCM on adhesion molecules was accompanied by an increase in monocyte adhesion. Inhibition of TNF-alpha production reduced monocytes adhesion slightly but significantly (18%, p < 0.05), whereas anti-IL-1 beta antibody decreased adhesion by 48% (p < 0.001). These results show that adherent monocytes released cytokines and antagonists that affect leukocyte adhesion receptors on endothelium differently from recombinant cytokines. E-selectin expression--and to a lesser extent ICAM expression--is modified, resulting in a modulation of leukocyte adhesion to endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion↗
PubMed1993

A versatile ELISA-PCR assay for mRNA quantitation from a few cells.

Gene expression studies require a sensitive and quantitative assay of mRNA amounts present in small samples. We describe a general method of quantifying specific mRNA quickly and easily from purified RNA or directly from a few cells by PCR and enzyme-linked immunosorbent assay (ELISA) revelation of the resulting products (sensitivity of the last step: < 0.1 fmol). Cells are digested and the total cellular RNA is reverse-transcribed and then amplified with 5' and 3' primers; the former being 5' biotinylated. The amplification product is captured on avidin-coated microplates and quantified by hybridization with a digoxigenin-labeled internal oligonucleotide probe. After revelation with an anti-digoxigenin alkaline phosphatase coupled antibody (anti-DIG-AP1), the amount of hybridized probe is determined by optical reading. The results can be easily converted to absolute values by comparison with an external DNA standard curve. An internal DNA or RNA standard can also be used. The method we describe can be adapted to any cellular or viral gene of known sequence in a matter of days. Since it uses nonradioactive probes, commercially available reagents and standard microplate readers, it is inexpensive and could be automated easily. In this study, interleukin-2 mRNA expression could be studied in as few as 40 Jurkat cells. It was also possible to quantify human immunodeficiency virus (HIV) DNA from 1500 to 1.5 copies out of 1.5 x 10(5) human genomic DNA copies.

Avidin↗
PubMed1992

Molecular mechanism of blood monocyte adhesion to vascular endothelial cells.

The blood monocytes adhere to endothelial cells unstimulated and after stimulation by interleukin-1, tumor necrosis factor or other mediators. This process is mediated through specific molecules on both endothelial cells and monocytes. Using specific monoclonal antibodies and molecular cloning several families of molecules involved in leukocyte endothelial cell interaction have been defined. Leukocyte adhesion molecules include the three beta 2 integrins (CD11/CD18 molecules), VLA-4 and the L-Selectin. E-Selectin (ELAM-1), P-Selectin (GMP-140) and receptors of the immunoglobulin superfamily (ICAM-1, ICAM-2 and VCAM-1) are expressed on endothelial cells in basal conditions and after activation. It has been shown that these adhesive molecules are involved in blood monocyte adhesion to endothelial cells. Monocytes from patients with diabetes mellitus had an increased adhesion to endothelial cells in culture. As estimated by flow cytometry CD11b/CD18 expression on diabetic monocytes was increased. Pentoxifylline reduced CD11b/CD18 expression on normal and diabetic monocytes. This effect was associated to a decrease in monocyte adhesion to endothelial cells.

Cell Adhesion↗
PubMed1990

Leukocyte adhesion to endothelial cells.

The adhesion of leukocytes to endothelium is a physiological phenomenon which is the first step for leukocyte emigration. The adhesion can be dramatically increased in pathological situations such as inflammation and vascular diseases. The molecular basis of leukocyte-endothelium interaction has been largely investigated in the last ten years. Using monoclonal antibodies it is possible to characterize the leukocyte adhesion molecule (LeuCAM) also named CD11/CD18 complex. These molecules responsible for leukocyte adhesion are heterodimers consisting of a common beta subunit and different subunit CD11a/CD18 corresponding to LFA-1; CD11b/CD18 to Mac1/Mol; CD11c/CD18 to GP150-95. Beside these receptors, other leukocyte structures such as the fibronectin receptors are involved in the adhesive process. On the endothelial cell side specialized structures implicated in leukocyte adhesion have been identified. Structures like Intercellular Adhesion Molecule (ICAM) are expressed on endothelial cells in the absence of stimulation, while other receptors Endothelial Leukocyte Adhesion Molecule (ELAM) are only detectable on activated endothelial cells. Cytokines such as IL-1 induced the expression of ELAM, increased the number of ICAM and Human Leukocyte Antigens (HLA) DR, DP, DQ. In various pathological circumstances, namely extracorporeal circulation, Acute Respiratory Distress Syndrome (ARDS), hypercholesterolemia and diabetes mellitus increased leukocyte adhesion has been reported and is potentially responsible for vascular damage. Therefore, the modulation of leukocyte-endothelial cell interactions is a possible target for antithrombotic and antiatherosclerotic therapy.

Cell Adhesion↗
PubMed1989

Modulation of platelet function by SIN-1A, a metabolite of molsidomine.

Molsidomine or its active metabolite SIN-1A have antithrombotic properties in experimental models. This effect seems to be related, at least in part, to their antiplatelet activities. SIN-1A inhibited platelet adhesion to collagen, platelet aggregation, and the release reaction in in vitro experiments. SIN-1A acts as an early step of platelet activation by inhibiting calcium influx and phospholipase activity, which leads to inhibition of thromboxane formation and fibrinogen binding. Antiplatelet properties were observed after oral absorption in healthy volunteers and in patients with myocardial infarction after intravenous infusion.

Collagen↗
PubMed1988

Prevention of postoperative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement.

A double blind randomized trial comparing subcutaneous enoxaparin (40 mg once daily) with standard unfractionated calcium heparin administered at a dose of 5,000 units every 8 hours in patients undergoing elective hip replacement has been performed. Treatment regimens began 12 hours preoperatively with enoxaparin, 2 hours preoperatively with standard unfractionated calcium heparin, and were continued for 15 days or until discharge. Venography was performed in all patients. Two hundred thirty-seven patients were included in the study: 113 received unfractionated heparin and 124 received enoxaparin. The incidence of proximal deep vein thrombosis was reduced from 18.5% in the unfractionated heparin group to 7.5% in the enoxaparin group (p = 0.014), and the incidence of total deep vein thrombosis was similarly reduced from 25% to 12.5% (p = 0.03). There were two major bleeding episodes and one minor bleed in the enoxaparin group compared to two minor bleeds in the unfractionated heparin group. Patients who received enoxaparin required fewer red blood cell transfusions and had a significantly higher hemoglobin on postoperative days 3 and 4. Thus prophylaxis with enoxaparin, 40 mg once daily, is simple, safe and more effective than standard low dose unfractionated heparin in preventing deep vein thrombosis in patients undergoing elective hip replacement.

Aged↗
PubMed1988

Relative content of isoaccepting tRNAs for glycine and proline in avian tendon cells with different rates of procollagen synthesis.

The relative amounts of iso-tRNAsGly and iso-tRNAsPro existing in chick embryo tendon are indicative of a specialization of the tRNA population for collagen synthesis. These amounts are not modified (i) in primary avian tendon (PAT) cells in culture for which the procollagen production varies from about 10% of total protein synthesis to 60% and (ii) in tendons from immature chicks, which show a 3-fold decrease of procollagen production with increasing age. The characteristic tRNA pattern was not maintained in cells which had lost the ability to make high levels of collagen as observed in the cases of: (i) PAT cells reaching confluency; (ii) virus-transformed PAT cells and (iii) tendon from adult chick. Our data are consistent with the idea that tendon tRNA specialization for collagen synthesis is a differentiation feature independent of the expression level of the collagenic function but related to its maintenance.

Aging↗
PubMed1988

Distribution of isoaccepting tRNAs and codons for proline and glycine in collagenous and noncollagenous chicken tissues.

The relation between codon usage and tRNA content for proline and glycine, the major constituents of collagen, was studied in two tissues: the magnum of laying hen oviduct and the leg tendons of chick embryo where collagen is produced. Although the relative contents of tRNA(GCCGly) and tRNA(IGGPro) in tendons, as compared to magnum indicate a specialization of the tRNA population for collagen synthesis, the distribution of the preponderant codons in collagen mRNA is correlated but at a lesser extent to that of their cognate tRNAs.

Animals↗
PubMed1987

[Anti-HLA immunization following transfusions of leukocyte-poor blood].

We have followed the evolution of leucocyte antibodies in patients receiving multiple blood transfusions of leucocyte-poor blood. The number of leucocytes present in one unit of transfused blood was always less than 1 X 10(8). We observed that such preparations were able to re-stimulate antibodies which had disappeared, but especially they were able to provoke a first immunisation in some patients never immunized in the past. The specificities of these antibodies corresponded to one or several antigens present in the donor of the transfused unit. This study shows that leucocyte immunisation cannot always be avoided in spite of the selection of blood products containing very few white cells.

Adolescent↗
PubMed1987

[Ex vivo study of blood platelet activation in healthy subjects or coronary disease patients after oral intake of molsidomine].

Platelet activation (aggregation, serotonin release, TXB2 synthesis) was studied in 8 normal subjects and 5 patients with unstable angina before and after molsidomine treatment. Serotonin release was the most altered parameter after molsidomine treatment in the group of normal subjects. No significant effect could be detected in patients since platelet reactivity varied in a wide range.

Administration, Oral↗
PubMed1985

Inhibition of Rous sarcoma virus production by formycin.

The effect of formycin, an adenosine analog, on the growth of chick embryo fibroblasts and on Rous sarcoma virus (RSV) production was studied. An adverse effect on cell proliferation was observed in the presence of 10 microM formycin. Treatment with 5 microM formycin for 24 hr reduced by a factor of about 1000 the yield of infections progeny whereas the cell growth remained unaltered. Moreover the few particles released in the presence of formycin showed a markedly decreased ability to synthesize viral cDNA. This impairment was shown to be related to a nonfunctional primer tRNA.

Animals↗
PubMed1984

[Biological studies and research of immunologic deficiencies in blood donors from a prison environment].

The prison population may be considered as a population at risk for AIDS. Biological parameters were studied in order to detect significant anomalies commonly observed in AIDS patients. With respect to are age matched control population of donors, there are no statistically significant differences concerning the nutritional and inflammatory states of the two populations. The investigation of the humoral immunity shows comparable levels of circulating antibodies in the two groups: a high level of anti-cytomegalovirus and anti-herpes antibodies is more frequently found in the penal population. The markers for hepatitis B were also studied. None of the individuals is a carrier of the HBs antigen. The percentage of individuals having biological markers of hepatitis B is higher in the at risk group (45%) than in the control group (10%). The evaluation of the cell-mediated immunity shows that there are no significant differences between the mean values found in the two groups for OKT3, T11, OKT4 and OKT8. There is no inversed OKT4/OKT8 ratio in the at risk group while one donor in the control group shows an inversed OKT4/OKT8 ratio.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Assessment of erythrocyte deformability by constant flow filtration technique: analysis of factors influencing the initial pressure.

When filtering red blood cells (RBC) resuspended into buffer at constant flow, the pressure-time curve is dependent on erythrocyte deformability (E.D) and also on the plugging of pores by RBC or leukocytes (WBC). To understand the influence of these 3 factors, we used an apparatus with: 1) a constant flow syringe (Bioblock) (1.56 ml/mn); 2) a pressure transducer (Statham P23 ID); 3) a recorder (Gould); 4) a 5 micron polycarbonate filter (Nuclepore) housed in a lucite block according to USAMI & al. (1). Resuspensions of RBC from 4 to 14% haematocrit with 0 to 600 WBC/mm3 were investigated. Results indicate that: 1/ The first inflexion point of the pressure-time curve (initial pressure leading to calculation of beta) is related to the RBC's deformability; 2/beta is (in our experimental conditions) dependent on the WBC number; 3/beta seems very sensitive to deformability changes as shown by rapid increases induced by osmolarity changes.

Erythrocytes↗