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Biomedical subjects

I Durand

Publications and source records attributed to I Durand.

72 records · Page 4Linked to original sources

Interleukin-7 induces the proliferation of normal human B-cell precursors.

In the present study, we investigated the effects of human recombinant interleukin-7 (IL-7) on the proliferation of enriched hematopoietic cells isolated from human adult and fetal bone marrow (BM). In cultures of CD34+ cells, IL-7 was found to induce dose-dependent incorporation of 3H-thymidine (3H-TdR), but had no demonstrable effect on the development of myeloid colony-forming cells. Numbers of B-cell precursors (BCP), initially present within CD34+ populations and which included a CD34+CD20+ subset, were significantly increased when CD34+ BM cells were cultured in the presence of IL-7. This effect was most striking on CD20+ BCP, and resulted at least partly from higher numbers of cycling cells as indicated by Hoechst 33342 fluorescence (Calbiochem, Behring Diagnostics, La Jolla, CA). These results indicate that IL-7 promotes the growth of BCP within the CD34+ compartment. In line with the B-lineage affiliation of CD34+ target cells, committed BCP (CD10+ CD19+ surface IgM-) isolated from BM were also found to proliferate in response to IL-7. Interestingly, this effect of IL-7 was strongly potentiated by the addition of IL-3. Taken together, and in accordance with previous observations on murine cells, our data indicate that IL-7 acts as a growth factor during the ontogeny of human B lymphocytes.

Adult↗

Potentiation of early hematopoiesis by tumor necrosis factor-alpha is followed by inhibition of granulopoietic differentiation and proliferation.

We have previously shown that tumor necrosis factor-alpha (TNF alpha) strongly potentiates interleukin-3 (IL-3)-induced short-term proliferation of human CD34+ hematopoietic progenitor cells (HPC). Using longer term cultures of CD34+ HPC, we demonstrate here that this initial potentiation ceases after 10 to 12 days; whereupon TNF alpha displays inhibitory effects. Thus, TNF alpha was found to inhibit cells of granulocytic affiliation while it potentiates the development of maturing cells of the monocytic lineage both in liquid and semi-solid (day 14 colony-forming unit) cultures. TNF alpha was demonstrated to reversibly block granulocytic differentiation at the level of uncommitted CD13-, CD15- blast cells that accumulate in IL-3 + TNF alpha cultures. Furthermore, growth of committed granulocytes (CD15+) from IL-3 cultures was also inhibited by TNF alpha through an arrest of cell cycle in G0/G1. Finally, the use of neutralizing anti-TNF alpha monoclonal antibody and limiting dilution studies indicate that the inhibitory effects of TNF alpha are direct. Taken together, our data demonstrate that, following a phase of potentiation of proliferation of early HPC, TNF alpha displays direct inhibitory effects due to negative interference with both granulocytic differentiation and proliferation of granulocytic cells.

Antibodies, Monoclonal↗

IL-4 and IL-2 upregulate the expression of antigen B7, the B cell counterstructure to T cell CD28: an amplification mechanism for T-B cell interactions.

We recently generated mAb 104 which is specific for the B cell activation antigen Ag B7. With this we studied the regulation of Ag B7 expression on normal tonsillar B lymphocytes as well as the activities of B7+ and B7- activated B cells. SAC and to a lesser extent anti-IgM antibody upregulated Ag B7 and this was further enhanced by IL-2 and most notably IL-4. Ag B7 was expressed on virtually all sIgG+ and sIgA+ B cells and approximately half of the sIgD+ and sIgM+ B cells. SAC-stimulated B7+ B cells proliferated and produced IgM, IgG and IgA in response to IL-2 and IgM and IgG in response to IL-4. SAC-stimulated B7- B cells proliferated and produced only IgM in response to IL-2 and IL-4. Considering that Ag B7 has recently been shown to be the counterstructure of the T cell CD28 and that CD28 triggering strongly enhances cytokine production by T cells, it is likely that the CD28/B7 interaction represents an important amplification phenomenon in T-B cell interaction leading to humoral immune responses. The preferential expression of Ag B7 on IgG and IgA committed cells suggests that CD28/B7 interaction may be more specific to secondary antibody responses provided by memory T and B cells.

Antigens, Differentiation, T-Lymphocyte↗

[Value of ambulatory blood pressure monitoring in borderline hypertension in the child].

This study was undertaken to evaluate the reliability of ambulatory blood pressure monitoring (ABPM) in children and its diagnostic value in teenagers with borderline hypertension. The apparatus used was a Nippon Colin (NC) ABPM 630 which simultaneously obtains BP levels by the auscultatory and oscillometric methods. Among 61 children (mean age 12 +/- 3 years), proportion of measurement failures was 14% (470/3399) for oscillometry, 26.5% (893/3360) for auscultation, and 2.7% for both methods together. Comparison of conventional auscultatory blood pressure measurements (mercury manometer) and simultaneous NC-auscultatory BP values (50 pairs) showed slightly lower diastolic blood pressure values with the NC monitor (-3.8 +/- 4.9 mmHg, p less than 0.01). Comparison of blood pressure values provided by the two NC methods (1580 pairs) demonstrated slightly higher systolic blood pressure values (+2.5 +/- 4 mmHg; p less than 0.001) and slightly lower diastolic blood pressure values (-5 +/- 4 mmHg; p less than 0.001) with the oscillometric method. Thirty-four ambulatory blood pressure recordings were obtained in 28 children (mean age 13.3: range 8-17) with outpatient clinic blood pressure values suggestive of borderline hypertension. Numbers of ambulatory blood pressure readings were 44 +/- 5 during the day and 9 +/- 1 during the night. The mean of daytime blood pressure values was compared with reference blood pressure values obtained at rest in normal French children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

7-amino-4-methylcoumarin-3-acetic acid-conjugated streptavidin permits simultaneous flow cytometry analysis of either three cell surface antigens or one cell surface antigen as a function of RNA and DNA content.

We have investigated the use of the new coumarin dye AMCA (7-amino-4-methylcoumarin-3-acetic acid), as a fluorochrome for multiple color fluorescence analysis by flow cytometry. AMCA is now commercially available as a streptavidin conjugate. Its excitation wavelength is optimal at 351/364 nm with a UV argon ion laser and it emits optimally in the blue at 450 nm. AMCA-conjugated streptavidin yields a fluorescence intensity comparable to that obtained with FITC-streptavidin. The emission spectrum of AMCA does not interfere with that of FITC and phycoerythrin and thus permits triple color analysis of cell surface antigens without requiring the need for important electronic compensation. A unique feature of AMCA conjugates was the possibility to determine the expression of a surface antigen as a function of cellular RNA and DNA levels stained with acridine orange. AMCA conjugates will thus facilitate multiple color analysis by flow cytometry.

Antigens, Differentiation↗

Interleukin-4 receptors on human blood mononuclear cells.

We have studied regulation of the expression of the interleukin-4 receptor (IL-4R) on human blood mononuclear cells (PBMC) using both 125I-IL-4 binding assay and flow cytometric analysis of biotinylated IL-4 (B-IL-4) binding. PBMC express approximately 300 high-affinity IL-4R per cell (Kd = 25-100 pM). Activation of PBMC for 60-80 hr by phytohemagglutinin (PHA) or concanavalin A (Con A) results in a 2- to 4.5-fold increase of IL-4R number without alteration of IL-4R affinity for IL-4. Binding of B-IL-4 showed that IL-4R expression is upregulated on virtually all PHA-stimulated PBMC, whereas it mostly concerns larger cells among Con A-activated PBMC. Reculture of PHA-blasts with 1 nM IL-4 further upregulates IL-4R expression to a level approximately 10-fold higher than observed on freshly isolated PBMC. Interestingly, IL-4 is able to reinduce high IL-4R levels on cells that have been deprived of IL-4 for 20 hr and IL-2 is almost as efficient. Finally, SDS-PAGE analysis of IL-4-binding molecules on unstimulated, PHA- and PHA/IL-4-activated PBMC revealed the same three peptides of MW 140-130, 80-75, and 70-65 kDa, as shown on human cell lines.

Biotin↗

Human interleukin 4 down-regulates the surface expression of CD5 on normal and leukemic B cells.

CD5 is a pan-T cell antigen which is expressed on a minor subset of normal B lymphocytes and on most chronic lymphocytic leukemia B cells (B-CLL). In this study, it is demonstrated that interleukin (IL) 4 down-regulates the surface expression of CD5 on tonsil B cells and B-CLL cells, but not on T cells. IL 4 inhibits both the spontaneous and the phorbol myristate acetate (PMA)-induced hyperexpression of CD5 on tonsil B cells. In contrast, IL 4 only suppresses the PMA-induced hyperexpression of CD5 on B-CLL, whereas the spontaneous CD5 expression is essentially unaffected. The IL 4 concentrations required to down-regulate CD5 are the same as those required to up-regulate CD23. The IL 4-mediated down-regulation of CD5 is an intrinsic property of this IL, since an anti-IL 4-neutralizing antiserum blocks this effect. Interferon (IFN)-gamma, which inhibits the IL 4 induced CD23 expression, does not block the IL 4-induced down-regulation of CD5. Recombinant IL 1 alpha, IL 2, IL 3, IL 5, IL 6, tumor necrosis factor (TNF)-alpha, IFN-gamma and granulocyte macrophage colony-stimulating factor neither inhibit nor stimulate CD5 expression on B cells, therefore suggesting that the capacity to down-regulate CD5 expression on B cells is specific to IL 4.

Antigens, Differentiation↗

Sequential loss of CD34 and class II MHC antigens on purified cord blood hematopoietic progenitors cultured with IL-3: characterization of CD34-, HLA-DR+ cells.

The expression of class II MHC and CD34 antigens on human cord blood hematopoietic progenitor cells (HPC) was investigated upon culturing in the presence of interleukin-3 (IL-3). HPC isolated by "panning" according to their expression of CD34 coexpressed HLA-DR and HLA-DP, and the majority of the CD34+ HPC also expressed HLA-DQ. In the presence of IL-3, the expression of CD34 and class II MHC antigens was found to be gradually lost in culture. Loss of CD34 expression preceded loss of HLA-DR expression. After eight days of culture, CD34-, HLA-DR+ blast cells were obtained that strongly proliferated in response to IL-3, GM-CSF, G-CSF, and M-CSF, and that had the capacity to generate macrophage and granulocyte colonies. After ten days of culture in IL-3, a population of CD34- cells that expressed low levels of HLA-DR (HLA-DRlo) was obtained by FACS-sorting. These CD34-, HLA-DRlo cells lacked colony-forming activity while the population expressing high levels of HLA-DR (HLA-DRhi) contained great numbers of colony-forming cells, and proliferated stronger in response to CSFs than the HLA-DRlo fraction. Finally CD34-, HLA-DR- cells that appeared later in the cultures (14 to 16 days) represented more differentiated cells with only marginal proliferative and no clonogenic capacity. These data indicate that whereas CD34 expression is associated with the multilineage potential of the HPC, HLA-DR expression correlates with overall proliferative capacity of hematopoietic cells during culture in IL-3.

Antigens, CD34↗

Nurse/patient dependency in community nursing.

Patient/nurse dependency measures developed in the setting of acute hospital care were shown to be not wholly appropriate to community nursing. In a literature search undertaken to locate a tool suitable for measuring nurse/patient dependency in the community, a number of studies were found with material relevant to the subject. It appeared that age and mobility were determining factors in the allocation of district nursing time, but the complexity of other variables, including home conditions and the presence or absence of other carers, defied precise measurement. A functional assessment scale was found which had been developed for assessing and monitoring patients in the community and this might be utilised as a dependency measure if timings could be attached. A small pilot study undertaken in 1984/5 to investigate this possibility was followed by a larger study completed in 1987.

Activities of Daily Living↗

Effects of admission to a nursing unit.

This paper describes the results of a study of elderly patients admitted to hospital with fractured neck of femur, cerebral vascular accident or amputation of a lower limb who were, immediately post-crisis, transferred to a unit where nursing was perceived as the chief therapeutic activity. Patients' outcomes were compared with a control group who followed a normal patient pathway, either remaining in an acute hospital ward until discharge or being transferred to a community hospital for part of their stay. The study was a modified replication of a small pilot study carried out between 1983 and 1985.

Aged↗