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Biomedical subjects

P Merville

Publications and source records attributed to P Merville.

At least 37 records · Page 2Linked to original sources
PubMed1998

Color Doppler sonography in early renal transplantation follow-up: resistive index measurements versus power Doppler sonography.

OBJECTIVE: This study was designed to compare power Doppler images of perfusion with interlobar resistive index measurements obtained during the early monitoring of renal graft transplant to diagnose cortical perfusion abnormalities and assess prognosis. SUBJECTS AND METHODS: Thirty-one patients underwent color Doppler sonography (4-7 MHz and 7-10 MHz) on day 6+/-2 after renal transplantation. Cortical vessel density was assessed visually and classified as either normal or decreased. Twelve months after transplantation, the results of power Doppler imaging and the levels of resistive index were reviewed in light of clinical and laboratory findings, graft biopsy results, and functional outcome. RESULTS: No significant relationship was observed among power Doppler grades, levels of resistive index, and renal function. Power Doppler grades and resistive index levels failed to allow us to distinguish between tubulopathy and rejection. However, we found a statistically significant relationship between renal function at 12 months after transplantation and power Doppler grade (p = .04). CONCLUSION: This study suggests that color Doppler sonography is insensitive in revealing and in allowing radiologists to differentiate the causes of graft dysfunction. However, power Doppler sonography allows a prediction of the functional recovery of the graft at 12 months after transplantation not provided by resistive index levels.

Adult↗
PubMed1997

CD40 ligand stimulates proinflammatory cytokine production by human endothelial cells.

Functional expression of CD40 has recently been described on the surface of HUVEC, and activation of these cells with CD40 ligand (CD40-L) leads to increased adhesion molecule expression. Here, we analyzed the effect of CD40 triggering on cytokine production by HUVEC. CD40-L-transfected fibroblasts, in contrast to their untransfected counterparts, as well as a soluble recombinant human CD40-L/murine CD8alpha chimeric molecule were able to importantly increase (by a mean of fourfold) the production of leukemia inhibitory factor (LIF) by HUVEC. CD40-L displayed an additive effect with IL-4, IL-1alpha, and TNF-alpha on the enhancement of LIF secretion. Cyclosporin A did not affect LIF synthesis by resting or CD40-L-activated HUVEC, whereas dexamethasone diminished the basal level of LIF production and abrogated the CD40-L effect. The secretions of two other proinflammatory cytokines, granulocyte-macrophage CSF and IL-6, were also increased in the presence of CD40-L. However, CD40-L neither affected HUVEC proliferation nor rescued them from IFN-gamma- and TNF-alpha induced apoptosis. Together, these results indicate that endothelial cell activation by CD40-L may play an important role not only in leukocyte recruitment through enhancement of adhesion molecule expression, but also in the maintenance of an inflammatory loop through the increase in proinflammatory cytokine secretion.

Apoptosis↗
PubMed1996

Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts.

Plasma cells represent the final stage of B lymphocyte differentiation. Most plasma cells in secondary lymphoid tissues live for a few days, whereas those in the lamina propria of mucosa and in bone marrow live for several weeks. To investigate the regulation of human plasma cell survival, plasma cells were isolated from tonsils according to high CD38 and low CD20 expression. Tonsillar plasma cells express CD9, CD19, CD24, CD37, CD40, CD74, and HLA-DR, but not CD10, HLA-DQ, CD28, CD56, and Fas/CD95. Although plasma cells express intracytoplasmic Bcl-2, they undergo swift apoptosis in vitro and do not respond to CD40 triggering. Bone marrow fibroblasts and rheumatoid synoviocytes, however, prevented plasma cells from undergoing apoptosis in a contact-dependent fashion. These data indicate that fibroblasts may form a microenvironment favorable for plasma cell survival under normal and pathological conditions.

Antigens, CD↗
PubMed1995

Generation of memory B cells and plasma cells in vitro.

After germinal center B cells undergo somatic mutation and antigen selection, they become either memory B cells or plasma cells, but the signal requirements that control entry into either pathway have been unclear. When purified human germinal center cells were cultured with interleukin-2, interleukin-10, and cells expressing CD40 ligand, cells with characteristics of memory B cells were generated. Removal of CD40 ligand from the system resulted in terminal differentiation of germinal center B cells into cells with the characteristics of plasma cells. These results indicate that CD40 ligand directs the differentiation of germinal center B cells toward memory B cells rather than toward plasma cells.

ADP-ribosyl Cyclase↗
PubMed1995

High frequency of IL-10-secreting CD4+ graft-infiltrating T lymphocytes in promptly rejected kidney allografts.

IFN-gamma and IL-10 secretion by sorted T cell subsets of irreversibly rejected kidney graft-infiltrating cells (GIC) and normal PBMC was studied by ELISPOT. The low spontaneous frequency of IFN-gamma-producing cells (IFN-gamma-PC) was strongly increased by anti-CD3 activation within unsorted, CD3+CD4+, and CD3+CD4- subsets of GIC and PBMC. In contrast with PBMC, IL-10-PC from GIC were at higher frequency within CD4+ cells than among CD4- ones (P < 0.03). Four kidneys removed after 3.7 +/- 0.8 months showed acute vascular rejection, high frequency of activated CD4+ IL-10-PC (118 +/- 68 per 10(4) cells), and high percentage of anti-class II antibody reactivity (87.6 +/- 6.3%). In contrast, four patients with kidneys removed later (53.7 +/- 1.6 months, P = 0.02) displayed chronic rejection with superimposed acute cellular rejection, low frequency of CD4+ IL-10-PC (7.0 +/- 3.0 per 10(4) cells, P = 0.02), and low percentage of anti-class II antibody reactivity (12.9 +/- 6.1%, P = 0.02). Thus, accelerated vascular rejection appears to be associated with preferential production of IL-10 by activated CD4+ GIC, which may act by shifting the effector arms of alloreaction toward humoral responses.

Acute Disease↗
PubMed1995

T cell-induced B cell blasts differentiate into plasma cells when cultured on bone marrow stroma with IL-3 and IL-10.

B lymphocytes activated by T cells in secondary lymphoid organs mature into plasma cells after migration into the medullary cords of these organs, mucosal lamina propria or bone marrow. To analyze each step leading to plasma cell generation, we set up a two-step culture system of purified tonsillar B cells. In a primary stage, B cell blasts were generated by co-culturing B cells with an irradiated T cell clone activated with immobilized anti-CD3. In a secondary step, culturing these blasts on bone marrow stromal cells (BMSC) induced them to secrete large amounts of IgG, as well as some IgM and IgA. Other fibroblast-like cell lines were less efficient at sustaining the differentiation of blasts into Ig-secreting cells, suggesting that these are specific properties of BMSC. Addition of IL-3 and IL-10 further stimulated IgG secretion by B cell blasts cultured on BMSC, mostly the IgG1 subclass. These two cytokines probably acted through different pathways, as (i) the effect of IL-3 but not IL-10 was dependent upon prolonged T cell pre-activation and (ii) their combined stimulatory effect was additive. B cell blasts cultured on BMSC with a combination of IL-3 and IL-10 differentiated into non-proliferating plasma cells as determined by poor thymidine incorporation, typical cellular morphology, intense expression of intracytoplasmic Igs, very high levels of surface CD38 and lack of surface CD20.

Adult↗
PubMed1995

The ability of synoviocytes to support terminal differentiation of activated B cells may explain plasma cell accumulation in rheumatoid synovium.

To understand the accumulation of plasma cells within RA synovium, the ability of rheumatoid synoviocytes to support the differentiation of B cells into plasma cells was explored. Tonsillar B lymphocytes cultured over confluent monolayers of synoviocytes, secreted threefold more Igs (mainly IgM) than B cells cultured directly on plastic well. More importantly, synoviocytes enhanced by 14-fold the production of Igs (mainly IgG) by B cells costimulated with Staphylococcus aureus Cowan (SAC) particles. IL-10 and, in a lower extent, IL-2 increased Ig secretion in cocultures, and their combination was synergistic. In the presence of SAC, IL-2, and IL-10, synoviocytes increased by 13-884-fold the production of IgG, which reached 0.19 ng/cell per day. RA as well as normal synoviocytes were more potent than other adherent cell lines to support terminal B cell differentiation. Synoviocyte activity involved both a support of B cell survival, and an induction of the terminal differentiation of B cells into mature plasma cells with typical morphology, high levels of intracytoplasmic Igs, and CD20- CD38high surface expression. The present observation should permit the identification of molecules involved in the maturation of B cells into plasma cells, and in their accumulation in rheumatoid synovium.

Antibodies, Monoclonal↗
PubMed1995

[Production of IFN gamma, IL6 and IL10 by infiltrating cells of renal allografts and irreversible rejection: modulation by IL2 and IL4].

The frequency of isolated low density graft-infiltrating cells (GIC) secreting IFN gamma, IL6 and IL10 was studied in 8 cases of irreversible rejection of human renal allografts, using ELISPOT assays. The GIC were mostly CD8+ T cells although CD4+ T cells, B cells and macrophages could also be detected. In average, in 10(6) cells, 189 secreted IFN gamma, 747 IL10, and 17,114 IL6. Culture of GIC in the presence of IL2 resulted in an increase on the frequency of IFN gamma producing cells (IFN gamma-PC), in a dose dependent manner, with an optimal 6.5 fold increase at 50 U/ml. In contrast, 25 U/ml IL4 decreased the frequency of spontaneous and IL2 induced IFN gamma-PC. Furthermore, IL4 reduced the frequency of IL6-PC.

Graft Rejection↗
PubMed1993

Detection of single cells secreting IFN-gamma, IL-6, and IL-10 in irreversibly rejected human kidney allografts, and their modulation by IL-2 and IL-4.

The frequency of isolated low-density graft-infiltrating cells (GIC) secreting IFN-gamma, IL-6, and IL-10 was studied in 8 cases of irreversible rejection of human renal allografts, using ELISA and SPOT-forming cells (ELISPOT) assays. The GIC were mostly CD8+ T cells, although CD4+ T cells, B cells, and macrophages could also be detected. On the average, in 10(6) cells, 189 secreted IFN-gamma, 747 IL-10, and 17114 IL-6. Culture of GIC in the presence of IL-2 resulted in an increase in the frequency of IFN-gamma-producing cells (IFN-gamma-PC), in a dose-dependent manner, with an optimal 6.5-fold increase at 50 U/ml. In contrast, 25 U/ml IL-4 decreased the frequency of spontaneous and IL-2-induced IFN-gamma-PC by 71.3% and 52.8%, respectively. Furthermore, IL-4 reduced the frequency of IL-6-PC (56.8%). By this new approach to graft rejection, it becomes easier to determine cytokine profiles within an allograft and to study their modulation by different agents. It could be a useful model of study for the development of new treatment.

Adjuvants, Immunologic↗
PubMed1993

Effects of a low-protein diet on urinary glycosaminoglycan excretion in adriamycin-treated rats.

Adriamycin (ADR) induces glomerular damage in rats with persistent severe proteinuria which reaches a peak 15 days after a single 5 mg/kg intravenous (i.v.) injection. We studied in ADR-treated rats the effects of a low-protein (6%) diet (LPD) supplemented with keto acids on urinary protein and glycosaminoglycan (GAG) excretion and glomerular GAG contents. Animals were divided into three groups: group 1 was used as control, and groups 2 and 3 received a single i.v. injection of ADR; group 2 was fed a standard diet (21% protein) and group 3 an LPD. After ADR, group 2 developed heavy proteinuria and showed a progressive increase in urinary GAG excretion starting a few days after the beginning of proteinuria onset and persisting throughout the experiment. After ADR, group 3 (LPD treatment) did not develop proteinuria, and the level of urinary GAGs was comparable to that of controls. The glomerular GAG level in ADR-treated rats was greatly reduced as compared to controls; this decrease was partly eliminated in rats on an LPD. These results suggest that an LPD has a direct effect on cellular GAG production and turnover in ADR-induced glomerulonephritis.

Animals↗
PubMed1992

[In situ production of interferon gamma and interleukin 6 by infiltrating cells from human kidney allografts in irreversible rejection. Modulation by cytokines].

Using ELISPOT assays, we detected a significant number of cells secreting interferon-gamma and interleukin 6 among 8 irreversibly rejected kidney allografts compared with normal kidneys. Interleukin 2 increases the frequency of interferon-gamma producing cells and interleukin 4 decreases the frequency of both interferon-gamma and interleukin 6 producing cells.

Depression, Chemical↗