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Biomedical subjects

D Emilie

Publications and source records attributed to D Emilie.

At least 145 records · Page 8Linked to original sources
PubMed1990

[Glucocorticoids: mode of action and pharmacokinetics].

Glucocorticoids are used in therapeutics for their anti-inflammatory, anti-allergic and immunosuppressant activities. These effects are partly due to the ability of glucocorticoids to inhibit cell activation, since they block the transmission of cell stimulation signals through the cell membrane. They also inhibit the release of numerous cellular mediators, such as interleukins, prostaglandins, leukotrienes, etc. which intervene in immunological reactions. Finally, their cytostatic effect justifies their inclusion in many chemotherapeutic regimens. Although glucocorticoids have been widely used for several decades, many questions concerning their pharmacokinetics and mechanism of action remain unanswered.

Anti-Inflammatory Agents↗
PubMed1990

Cystic fibrosis patients' B-lymphocyte response is resistant to the in vitro enhancing effect of corticosteroids.

Cystic fibrosis is associated with an cAMP-regulated channel defect, which has been evidenced in many cell types including B lymphocytes. To document a B-cell dysfunction potentially related to this defect, we studied the in vitro IgG production by lymphocytes from 11 cystic fibrosis patients. B lymphocytes were co-cultured with autologous monocytes and stimulated with Staphylococcus aureus Cowan or with Nocardia-delipidated cell mitogen in the presence of low concentrations of IL2. Cystic fibrosis patients' cells produced amounts of IgG comparable with that of normal and control patients' cells. However, dexamethasone (10(-7) mol l-1) had no effect on the response of cystic fibrosis patients' cells, whereas it enhanced that of the latter two groups. This resistance of cystic fibrosis cells was true with concentrations of dexamethasone up to 10(-6) mol l-1, whereas this agent induced a dose-related enhancement from 10(-8) to 10(-6) mol l-1 in cultures of normal cells. Co-culture experiments showed that cystic fibrosis B lymphocytes themselves are resistant to the effect of dexamethasone. In contrast dexamethasone normally suppressed the anti-CD3 antibody-induced response of cystic fibrosis T cells in the presence of IL2 and the IL1 alpha- or beta-induced collagenase production of cystic fibrosis fibroblast cell lines. Thus cystic fibrosis B lymphocytes exhibit a selective defect which may interfere with the normal interactions between the hormonal and immune systems and may participate in the sensitivity of cystic fibrosis patients to bacterial bronchopulmonary infections.

Adolescent↗
PubMed1990

Production of interleukins in human immunodeficiency virus-1-replicating lymph nodes.

To document the in vivo interactions occurring between the immune system and HIV replicating cells, we analyzed using in situ hybridization the production of IL-1 beta, IL-6, IL-2, and INF-gamma in eight hyperplastic lymph nodes from HIV-1 infected patients. Numerous IL-1 beta- and IL-6-producing cells associated in clusters were detected in sinuses. Few individual IL-1 beta- and IL-6-producing cells were present in interfollicular and follicular areas. IL-2- and INF-gamma-producing cells were observed in all lymph node compartments, with a selective enrichment in germinal centers. The amount and distribution of IL-1 beta, IL-6-, and IL-2-producing cells in HIV lymph nodes were not different from those found in six HIV unrelated hyperplastic lymph nodes. In contrast, a higher level of INF-gamma production was observed in HIV-1 lymph nodes. The CD8+ cells that accumulate in germinal centers of HIV lymph nodes (and not in non-HIV germinal centers) were actively involved in this INF-gamma production. INF-gamma synthesizing cells were in direct contact with cells containing HIV core antigens and HIV RNA. Thus a high INF-gamma production may characterize anti-HIV T cell immune response, potentially contributing to control of viral spreading as well as to the development of follicle lysis.

Adult↗
PubMed1990

Syncytium induction by fresh HIV isolates: quantitative analysis using a transactivation beta-gal assay.

We used a quantitative bioassay (the beta-gal assay) to visualize and quantify syncytium induction by fresh HIV isolates. This bioassay is based on the transactivation by tat of a chimeric gene comprising an HIV-1 long terminal repeat (LTR) fused to a modified lacZ gene of Escherichia coli. The chimeric gene encodes a beta-galactosidase which is translocated to the nucleus. It allows the enzymatic staining of all nuclei from HIV-induced syncytia. Using this unequivocal assay (the beta-gal assay), we could assess the syncytium-inducing properties of fresh HIV isolates after only 4 days of coculture of patient lymphocytes with activated normal lymphocytes. Syncytium-inducing HIV isolates were detected in 11 out of 40 seropositive patients studied. They were isolated mainly from AIDS patients: eight out of 17 grade IV (according to Centers for Disease Control criteria) patients were infected with syncytium-inducing strains. However, of 23 grade II and III patients tested, syncytium-inducing HIV strains were isolated from three cases. These three patients displayed no detectable p24 antigenaemia and had a CD4+ cell count of greater than 300 cells/microliter. The in vitro replication rate of HIV grown from 36 patient blood samples was then examined by sequential p24 antigen measurements in coculture supernatants. The 10 samples leading to syncytium formation also exhibited the highest replication rate. The possibility of unequivocally detecting syncytium-inducing strains after only a few days of coculture will make this detection routine and rapid. In addition, the limited period of amplification required is a significant advantage as it minimizes the emergence of HIV variants selected during long-term in vitro cultures.

Acquired Immunodeficiency Syndrome↗
PubMed1990

IL-2 mRNA expression in Tac-positive malignant lymphomas.

Expression of the IL-2 receptor (Tac antigen/CD25) is documented in malignant lymphomas. Because IL-2 is a major lymphocyte growth factor, an IL-2-dependent growth could be involved in the proliferation of Tac-positive lymphomas. Indeed such a mechanism has been demonstrated experimentally for the growth of T-cell lines. To investigate this point in human lymphomas, we used in situ hybridization to analyze the expression of the IL-2 gene in 20 non-Hodgkin's lymphomas, among which 12 expressed the IL-2 receptor. Nine of these were anaplastic large cell lymphomas expressing the Ki-1-related antigen. We here show that IL-2-producing cells are present in all the lymphomas we analyzed. As a mean, there is no significant difference in the percentage of IL-2-producing cells between Tac-positive and -negative lymphomas. However, the level of IL-2 production is highly heterogeneous in both groups, and the highest density of IL-2-producing cells was observed in 2 Tac-positive lymphomas. Simultaneous detection of cellular antigens and of IL-2 mRNA demonstrates that IL-2 is produced by reactive T cells rather than by tumor cells. These results suggest that if IL-2 is involved in the growth of Tac-positive lymphomas, it acts as a paracrine, rather than an autocrine, factor.

Adolescent↗
PubMed1990

[Regulation of antibody production by monokines and glucocorticoids].

The antibody production by B lymphocytes is regulated by a number of interleukins produced by T lymphocytes and/or monocytic cells: IL-1, IL-2, IL-4, IL-5, IL-6 and interferons. This response is also under the influence of other mediators such a glucocorticosteroid hormones. The in vivo administration of pharmacological doses of steroids do not markedly suppress the in vivo antibody response to exogeneous antigens. This is due to a contrasting effect: they prefoundly inhibit the production of most interleukins whereas they directly stimulate B lymphocyte response. We recently analyzed the mechanisms of this latter phenomenon and showed that glucocorticosteroids synergize with the monocyte-derived cytokines IL-1 and IL-6 to potentiate the in vitro B lymphocyte differentiation.

Antibody Formation↗
PubMed1989

Visualizing interleukin 2 gene expression at the single cell level.

To analyze the expression of the interleukin (IL)2 gene at the single cell level, we have constructed a chimeric gene in which the regulatory sequences from the mouse IL2 gene were fused 5' proximal to the coding region of the Escherichia coli beta-galactosidase (lacZ) gene. Once stably introduced into a T cell hybridoma, the IL 2-lacZ reporter gene was shown to display a pattern of induction similar to the one observed for the resident IL 2 gene. Two points emerged from monitoring IL 2 expression for the resident IL2 gene. Two points emerged from monitoring IL 2 expression at the single cell level. First, upon activation the expression of the IL2-lacZ gene appears asynchronous. Second, at the peak of induction the percentage of beta-galactosidase+ cells never reached 100% and the level of beta-galactosidase reached among positive cells was highly heterogeneous within a cloned population of T cells. In combination with the possibility to sort viable lymphocytes according to lacZ expression, the IL2-lacZ reporter gene described herein should provide a way to isolate somatic cell mutants deficient in signal transduction by the T cell antigen receptor complex.

Animals↗
PubMed1989

HIV-associated endometritis.

Using immunohistochemical staining, in situ hybridization and a combination of both, we demonstrate here the replication of HIV in the endometrial stroma. Infected cells do not belong to the T-lymphocyte lineage but rather to a monocyte-macrophage cell type. This report suggests a possible relationship between HIV infection and endometritis. Moreover, HIV replication in endometrial tissues could play a role in heterosexual and materno-fetal transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Role of the LFA3-CD2 interaction in human specific B cell differentiation.

We examined the role of the lymphocyte function-associated (LFA)3 molecule in human B cell response. A mAb to this molecule did not influence B cell proliferation induced by anti-mu antibody and IL. In contrast, the same mAb inhibited the specific T-dependent B cell response induced by a particulate Ag. In the same line, two anti-CD2 mAb (directed toward the T11-1 and T11-2 epitopes) inhibited this response, whether used alone or in association. These inhibitions took place at an early stage of the response, and anti-LFA3 and anti-CD2 mAb acted on B cells and T cells, respectively. In contrast, when T cell help was provided by exogenous IL-2, the B cell response was resistant to the inhibitory effect of anti-LFA3 mAb. Taken together, these results indicate that the LFA3-CD2 pair play a major role in the direct T-B interaction required for T cell help.

Animals↗
PubMed1988

Induction of differentiation in human leukemic B cells by interleukin 2 alone: differential effect on the expression of mu and J chain genes.

The effects of interleukin 2 (IL2) on the proliferation and differentiation of B cells were analyzed separately using cells from two patients suffering from B-type chronic lymphocytic leukemia. The monoclonal B cells from these patients exhibited an opposite pattern of responsiveness upon in vitro culture with IL2 in the absence of other stimuli. In the first patient, IL2 alone was able to induce DNA synthesis and no Ig production. In the second patient, although no DNA synthesis was detected, B lymphocytes synthesized IgM upon stimulation with IL2 alone. Analysis of mRNA levels was performed on the cells of this latter patient after culture without or with IL2. In the presence of IL2 we observed a strong enhancement of C mu gene expression associated with an increase of the ratio between the secreted form and the membrane-bound form of mu mRNA. In contrast IL2 induced only a marginal enhancement of J chain mRNA. Thus, terminal B cell differentiation of selected monoclonal B cells can be obtained in the absence of DNA synthesis and IL2 alone can mediate this process. Moreover, IL2 can act at selective steps of the molecular events associated with IgM production. These results document the multiple effects of a given IL on the events leading to antibody production and strongly suggest that they can be conditioned by the maturation stage of a given responding cell.

B-Lymphocytes↗
PubMed1988

Glucocorticosteroid-dependent synergy between interleukin 1 and interleukin 6 for human B lymphocyte differentiation.

In order to analyze the effects of interleukin (IL) 6 on human in vitro Ig production B lymphocytes were activated by Staphylococcus aureus Cowan strain I (SAC) in the presence of low concentrations of IL2 (1 U/ml) and dexamethasone (10(-7) M). Previously we showed that this model of B cell response is completely monocyte dependent. We here demonstrate that, under these experimental conditions, IL6 is able to replace monocytes and stimulate Ig production provided IL1 is also present. Dose-effect curves show that these two monokines act synergistically. This synergy is demonstrable only in the presence of dexamethasone, when B lymphocytes are activated (by SAC) and when T cell help (provided by IL2) is present. It results in the production of both IgM and IgG. Both IL1 and IL6 have to be present during the first 48 h of culture to exert an optimal effect. These results show that IL6 may act on early (as well as on late) stages of normal B lymphocyte differentiation. Moreover, glucocorticosteroids potentiate the synergistic effect of IL1 and IL6 on their B lymphocyte target, an effect comparable to that exerted on hepatocytes.

B-Lymphocytes↗
PubMed1988

In vitro effects of B cell growth and maturation factor on B-CLL lymphocytes.

In the presence of anti-mu Ab, B-CLL lymphocytes are able to respond to cytokines such as IL2, BCGF and IFN-alpha. IL2 is most frequently an active factor. According to the B-CLL lymphocytes population, IL2 alone can induce growth or maturation of B cells. IFN-gamma and IL2 are inefficient on B-CLL lymphocyte proliferation, but they can profoundly modulate the response to IL2. IFN-gamma can synergize with IL2. In contrast IL4 profoundly and constantly inhibits the response to IL2.

B-Lymphocytes↗
PubMed1987

B cell differentiation and interleukin 2 (IL2): corticosteroids interact with monocytes to enhance the effect of IL2.

Upon in vitro activation by Staphylococcus aureus Cowan I strain (SAC) human peripheral blood B cells produce only marginal amounts of Ig when cultured in the presence of interleukin 2 (IL2; 10 U/ml). This response is only moderately increased by the addition of monocytes or of IL1. In the presence of dexamethasone (DM; 10(-7)-10(-8) M) microgram amounts of both IgM and IgG are produced in co-cultures of B cells and monocytes. This response is not modified by inhibitors of cyclooxygenase and is specifically inhibited by a monoclonal antibody interfering with the binding of IL2 to its receptor. This enhancing effect of DM is not observed in the absence of monocytes even if IL1 is added to the cultures. Moreover, monocytes pretreated with DM stimulate the response of B cells cultures in the absence of DM. Enhancement of Ig production by DM and monocytes could be demonstrated with B cells obtained from a patient suffering from a hyperlymphocytic form of B cell type chronic lymphocytic leukemia, and in this case only IgM was produced. Importantly, DM fully inhibited the IL2-dependent proliferation of these monoclonal B cells. Thus, physiological concentrations of DM can modulate monocytic function to enhance the differentiative effect of IL2.

Adrenal Cortex Hormones↗
PubMed1987

Antigen-induced and polyclonal B-cell responses in human peripheral blood lymphocyte cultures.

This work was designed to delineate the anti-hapten antibody (Ab) response induced by trinitrophenol-polyacrylamide (TNP-PAA) beads from the nonspecific B-cell response which concomitantly occurs in human peripheral blood mononuclear cell (PBMC) cultures. Indeed human PBMC produce consistent amounts of immunoglobulins when cultured at high cell density in the presence of fetal bovine serum, regardless of the presence of antigen. In contrast, the stimulation of such cultures by TNP-PAA leads to an Ab response characterized by the following: cells secreting anti-hapten Ab at a high rate (detected by a plaque-forming cel (PFC) assay); a 10-30 times enhancement in the number of hapten-specific binding cells (detected by a rosette-forming cell (RFC) assay); the production of anti-TNP IgM Ab (detected by an ELISA assay). The anti-TNP response is specifically triggered by the particulate antigen, as shown by the following: The TNP-PAA antigen induces a clear-cut increase in the amount of anti-TNP Ab whereas it only marginally increases that of total IgM. The anti-TNP Ab response is specifically abolished when anti-TNP RFC are depleted from the PBMC preparation before the initiation of the cultures. The anti-TNP Ab response is specifically abolished when PBMC are triggered by TNP-PAA in the concomitant presence of a soluble TNP-protein conjugate. These results demonstrate the ability of polymeric antigens to specifically activate human peripheral blood B cells.

Acrylic Resins↗
PubMed1987

[Diffuse disease of elastic tissue and hyperphosphoremia].

Pseudoxanthoma elasticum (PXE) is exceptionally associated with abnormal phosphate-calcium metabolism. On the other hand, significant hyperphosphataemia is present in tumoral calcinosis, with an occasional elastopathy resembling that of PXE. We report here the first case of diffuse elastic tissue disease associated with hyperphosphataemia in the absence of tumoral calcinosis. The patient, a 29-year old Gabonese, had severe arteritis of the lower limbs with linear calcifications of the aorta and major arteries of the limbs. Angioid streaks and calcifications were present in the retinas. The skin appeared to be normal, but histological examination of specimens from flexures showed abnormalities of the elastic tissue with many fibres being broken into small pieces and curled up. In a morphometric study of cutaneous elastic tissue these abnormalities were compared with those observed in a PXE patient and with normal elastic tissue. The abnormalities in our patient and in the PXE patient were similar. Compared to normal elastic tissue, there was a slight decrease in the total number of oxytalan and elaunin fibres. The elastic fibres were distinctly wider, longer and separated from each other by smaller spaces, but not more numerous than normally. The histopathological appearance of an artery removed during bypass surgery was similar to that of a PXE artery. The hyperphosphataemia was due to an increase in tubular absorption of phosphates without abnormalities of parathyroid hormone, or resistance to its phosphaturic effect or any other tubular disorder. It was little altered by aluminium carbonate, and it partially decreased after addition of calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

[Inappropriate secretion of antidiuretic hormone disclosing acute intermittent porphyria].

The authors report a case of acute intermittent porphyria in a 31-year old woman, revealed by inappropriate secretion of the antidiuretic hormone, a diagnosis confirmed by radioimmunoassay. Measurements of red cell urosynthetase made the diagnosis of porphyria certain and showed that the disease was familial, although clinically asymptomatic. Antidiuresis is not the only cause of hyponatraemia in acute intermittent porphyria. Similarly, psychic disorders are frequent in SIADH, but they are not necessarily due to acute intermittent porphyria.

Acute Disease↗