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Biomedical subjects

C Fourcade

Publications and source records attributed to C Fourcade.

15 recordsLinked to original sources

Interleukin-7 is a growth factor for Sézary lymphoma cells.

Sézary syndrome is a cutaneous T cell lymphoma characterized by infiltration of the skin by CD4+ cells. These cells generally respond poorly to mitogens and T cell activators. We have studied the action of IL1 to IL4, IL6, and IL7 on the proliferation of Sézary cells from 12 patients. With the exception of IL2 and IL7, the cytokines studied had no proliferative effect on these cells. Whereas IL2 had only a low proliferative capacity (two- to threefold increase) on peripheral blood mononuclear cells, recombinant IL7 constantly induced a very significant (3-40-fold increase) proliferative response, and was used successfully to generate cell lines in three out of eight cases. Growth of Sézary cell lines was shown to be strictly dependent on IL7, and after 2-5 wk of culture presented a switch to a homogeneous phenotype CD3+4+8-7- (except for one line that remained CD7+), with a typical morphology of Sézary cells. Their tumoral origin was demonstrated by the expression of the same T cell receptor-beta gene rearrangement as the patients' T cells. Importantly, cultured normal epidermal keratinocyte supernatants could support the growth of our Sézary lines. Furthermore, the proliferative activity contained in these supernatants was completely blocked by a monoclonal anti-IL7 antibody. These results suggest that IL7 may, therefore, represent an important cytokine in the physiopathology of cutaneous T cell lymphoma.

Adult

Epidermal keratinocyte-derived basophil promoting activity. Role of interleukin 3 and soluble CD23.

Human epidermal keratinocytes (EK) secrete factors able to sustain the proliferation of early myeloid cells and, in particular, the generation of basophils. This activity was previously attributed to IL-3, although no definitive in situ demonstration of this cytokine was provided. In regard to the possible physiological relevance of these data, we investigated herein the nature of EK-derived factors responsible for basophil promotion. Our data show that EK-derived supernatants (EK-sup) contain IL-3 as well as soluble CD23 (sCD23), both known for their colony stimulating activity. Messenger RNA for IL-3 and CD23 were also detected in EK. Blocking experiments using specific neutralizing monoclonal antibodies (mAb) further indicate that EK-derived basophil promoting activity is mainly due to the presence of IL-3 and sCD23 in EK-sup. Furthermore, by contrast to IL-3, sCD23 secretion by EK is cortisone sensitive and highly enhanced by IL-4, suggesting distinct regulatory mechanisms for their production.

Antibodies, Monoclonal

Human thymic epithelial cells produce interleukin-3.

Interleukin-3 (IL-3) is a hematopoietic growth factor suggested to be produced by activated T lymphocytes. Meanwhile, supernatants from human thymic stroma could promote the proliferation of myeloid stem cells. Thus, we investigated whether IL-3 accounts for this activity. Therefore, human thymic epithelial cells (TEC), fibroblasts, and adherent cells were isolated, and their culture supernatants assayed for myeloid colony promotion. Only supernatants from thymic epithelial cells supported colony-forming unit growth in semisolid media. This effect decreased following anti-IL-3 monoclonal antibody addition to these cultures. Furthermore, in situ hybridization showed the presence of IL-3 mRNA in epithelial cells. Effect of TEC culture conditions on IL-3 production by these cells was also studied. Together, these data show that IL-3 production is not the exclusive property of human activated T lymphocytes.

Antibodies, Monoclonal

Synergistic effect of interleukin 1 and soluble CD23 on the growth of human CD4+ bone marrow-derived T cells.

Low-affinity Fc epsilon receptor (Fc epsilon RII/CD23) is expressed by various human cells and known to be cleaved into soluble fragments (sCD23). Several biological activities were ascribed to these molecules. In this study, we have assessed the effect of recombinant 25-kDa sCD23 (rsCD23) on human bone marrow-derived T cells. Our results show that rsCD23 in synergy with recombinant interleukin 1 enhances mitogenic responsiveness of CD4+ T cells but does not affect CD8+ cell growth. Furthermore, rsCD23 synergizes autologous marrow cells in enhancement of CD4+ cell growth while CD23 monoclonal antibodies decrease accessory cell effect. Together, these data confirm cytokine-like activity of sCD23 on human T cell lineage.

Antigens, Differentiation, B-Lymphocyte

Thymic epithelial cell-derived supernatants sustain the maturation of human prothymocytes: involvement of interleukin 1 and CD23.

During their development, human CD7+ lymphoid stem cells migrate into the thymus where, following intimate contact with thymic tissue, they proliferate and differentiate into functionally mature T lymphocytes. In this study, we investigated the effect of thymic epithelial cell-derived supernatants (TEC-SN) on early CD7+CD2-CD3- thymocytes. Our results indicate that TEC-SN are able to promote CD2 and CD3/TcR alpha/beta expression by CD7+ precursors. This activity correlated with soluble CD23 and interleukin 1 levels in TEC-SN. Furthermore, monoclonal antibodies to these cytokines decreased in vitro maturation of prothymocytes. Thus, in addition to cell-cell interactions, human TEC produce cytokines able to support early steps of thymocyte differentiation.

Antigens, CD

Experimental bypass for sagittal sinus repair. Preliminary report.

Bypasses of the sagittal sinus, 2.5 mm in diameter, were carried out in 25 dogs with venous (13 cases) and arterial (12 cases) autogenous grafts, by classical microtechniques. Animals were sacrificed 10 to 75 days after the operation, average 40 days. The patency rate was 54% in the venous autograft group; in all cases, thrombosis occurred early and was due to technical factors. The immediate postoperative patency rate was 100% in the arterial graft group, but this type of graft showed a tendency to progressive occlusion because of extensive fibrosis of the arterial wall; thus the patency rate was 75% at the time of autopsy. This preliminary work demonstrates the technical feasibility of bypass procedure which could be used for sagittal sinus repair.

Animals

Detailed description of an implantable directional Doppler flowmeter.

A Doppler flowmeter and the necessary modifications for implantation are described in detail. Since only part of the electronics was implanted a phase-locked loop had to be introduced in order to keep the flow measurement directional. The proper working of the apparatus is demonstrated in vitro and in vivo. As an example the result of flow studies in the aorta and the pulmonary artery after homotransplantation of the lung in dogs are given.

Animals

[Experimental intracranial venous microsurgery. Bypass of the sagittal sinus for arterial or venous repair and preoperative measurement of the cerebral impedance in the dog].

By-passes of the sagittal sinus-which is 2,5 mm in diameter-were carried out with autogenous arterial or venous grafts, in 34 dogs, using the classical microtechniques (operative microscope, micro-instruments, micro-sutures...). Controls were done both 1 degree by angiography (direct sinography was the only convenient procedure to visualize the sinus and the by-pass) during survival, and 2 degrees by anatomical and histological examination after sacrifying the animals, on an average the 40th post-operative day (from the 10th to the 75th day). The early patency rate (within the first post-operative month) was 76 p. 100. All cases of early thromboses, which affected especially venous autografts, were related to technical insufficiencies. The late patency rate (after a one month follow-up) was only 64 p. 100, because of the secondary occlusion of some arterial autografts. All these late thromboses were related to an extensive fibrosis of the arterial wall.

Animals

Expression of CD23 by human bone marrow stromal cells.

CD23 is a surface antigen expressed by a variety of human hematopoietic cells and shown to display multiple biological functions. In present work, we assayed CD23 expression by human bone marrow (BM) or by stromal cells derived from this tissue. While freshly isolated BM-cells showed low CD23 expression, a subset of long term BM-culture (LTBMC)-derived stromal cells expressed CD23 mRNA at high levels in their steady state and secreted soluble CD23 in their culture supernatants. To assay the role of CD23 in LTBMC, these cultures were initiated in the presence of neutralizing anti-CD23 mAb. A dramatic decrease in total numbers of hematopoietic cells and CFU-GM recovery was observed in these cultures as compared to controls. These data suggest a role of CD23 expression in stroma cell functions and further confirm the ability of this antigen to regulate human hematopoietic cell development.

Antibodies, Monoclonal

Time dependent modifications in arterial flow in a transplanted pulmonary lobe.

Study of pulmonary arterial flow in the transplanted lung by means of an implanted ultrasonic flowmeter enables us: 1. To confirm results obtained by other methods (De Bono,8 Strider14 and Strandberg18): without specific treatment, rejection of graft causes increased peripheral resistances and the pulmonary arterial flow decreases progressively. 2. To prove by direct observation the existence in the treated animal of authentic precapillary shunts whose importance can cause the animal's death through functional disorder alone.

Animals