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Biomedical subjects

G Biron

Publications and source records attributed to G Biron.

13 recordsLinked to original sources
PubMed1992

Interleukin 4 protects chronic lymphocytic leukemic B cells from death by apoptosis and upregulates Bcl-2 expression.

B chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of slow-dividing and long-lived monoclonal B cells arrested at the intermediate stage of their differentiation. We previously showed that interleukin 4 (IL-4) not only inhibits but also prevents the proliferation of B-CLL cells. We report here that IL-4 protects the B-CLL cells from death by apoptosis (programmed cell death [PCD]). IL-4 inhibits spontaneous and hydrocortisone (HC)-induced PCD of highly purified B cells from 12 unselected CLL patients, as shown by sustained cell viability and lack of DNA fragmentation. IL-1, -2, -3, -5, -6, -7, tumor necrosis factor alpha, and transforming growth factor beta have no protective effect. The in vitro rescue from apoptosis by IL-4 is reflected by an increased expression of Bcl-2 protein, a proto-oncogene directly involved in the prolongation of cell survival in vivo and in vitro. Hence, IL-4-treated B-CLL cells express significantly more Bcl-2 than unstimulated, HC-treated, or fresh B-CLL cells. Furthermore, subcutaneous injection of IL-4 into one CLL patient enhances Bcl-2 protein expression in the leukemic B cells. These data may suggest that IL-4 prevents apoptosis of B-CLL cells using a Bcl-2-dependent pathway. Given our recent observations that fresh T cells from B-CLL patients express IL-4 mRNA, we propose that IL-4 has an essential role in the pathogenesis of CLL disease, by preventing both the death and the proliferation of the malignant B cells.

Adult↗
PubMed1992

Low-molecular weight B cell growth factor (BCGF-12KD) as an autocrine growth factor in B cell chronic lymphocytic leukemia.

The role of cytokines in the growth and spreading of human hematologic malignancies has been underlined in recent years. Here we report evidence that a human 12-kDa B cell growth factor (BCGF-12KD) may function as a growth stimulatory factor in B cell chronic lymphocytic leukemia (B-CLL). First, recombinant BCGF-12KD induced dose-dependent DNA synthesis in neoplastic B cells of four B-CLL patients tested. Second, seven different B-CLL clones secreted a BCGF-12KD-like product that accounted for their proliferation. A neutralizing monoclonal antibody (mAb; Ac8) directed against a BCGF-12KD synthetic peptide inhibited the spontaneous growth of the leukemic B cells. The same mAb blocked DNA synthesis in normal tonsillar B lymphocytes induced by the culture supernatant of spontaneously proliferating B-CLL cells. Finally, BCGF-12KD mRNA was expressed in freshly isolated (two of three patients) as well as in vitro proliferating B-CLL cells (three of three patients). These findings strongly suggest that BCGF-12KD can modulate the growth of B-CLL cells in vivo as well as in vitro. They may offer significant insights into the biology of this frequent B lymphoproliferative disorder.

Adult↗
PubMed1992

CD23 antigen regulation and signaling in chronic lymphocytic leukemia.

B lymphocytes from patients with chronic lymphocytic leukemia (B-CLLs), strongly express the CD23 antigen, a surface marker with significant prognostic importance in this disease. Because we previously reported that IL-4 shows a poor capacity for CD23 expression on B-CLLs, we first examined the possible mechanisms underlying CD23 overexpression on B-CLLs and found that mitogen-activated CLL T cells release soluble factors that are capable, in synergy with IL-4, of strongly inducing CD23. Using neutralizing Abs, we noticed that the T-cell-derived enhancing activity is entirely ascribed to the combined effects of IFN gamma (potent inhibitor of CD23 on normal B cells), TNF alpha (which has no effect on normal B cells), and IL-2 (which has a slight enhancing effect on both CLL and normal B cells). Furthermore, recombinant IFN gamma as well as IFN alpha, TNF alpha, and IL-2 (but not IL-3, IL-5, IL-6, IL-7, and lymphotoxin) significantly enhance CD23 protein and mRNA expression on B-CLLs, in the presence or absence of IL-4. Inasmuch as optimal CD23 expression absolutely requires the combination of IFN gamma, IL-2, TNF alpha (the production of which is increased in CLL disease), and IL-4, it was relevant to show that IL-4 mRNA is indeed expressed in fresh T-CLL cells. We next examined the possible role of CD23 in the regulation of B-CLL proliferation. Signaling through CD23 via ligation of the antigen by F(ab')2 anti-CD23 MAb but not Fab fragments inhibits the cytokine-induced B-CLL DNA synthesis. It is concluded that the CD23 gene is abnormally regulated in B-CLL disease and that cross-linking of CD23 molecule delivers a negative growth signal to the leukemic B cells.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1991

The in vivo expression of type B CD23 mRNA in B-chronic lymphocytic leukemic cells is associated with an abnormally low CD23 upregulation by IL-4: comparison with their normal cellular counterparts.

We recently reported that the sera of chronic lymphocytic leukemia (CLL) patients contained 3-500 times more soluble CD23 (or IgE-BF) than the sera of patients with other lymphoproliferative diseases or normal individuals and that their B cells (B-CLLs) overexpressed CD23 Ag. In the present report, we extended these studies and showed that CD5+ B cells from all CLL patients (n = 15) co-express CD23 Ag. We next identified two additional major differences between B-CLLs and normal adult B cells. First, in contrast to normal adult B cells which exclusively express type A CD23 mRNA, freshly isolated B-CLLs expressed both type B and type A CD23 mRNA. Second, although IL-4 is a potent inducer of type B CD23 mRNA on normal B cells, an optimal concentration of IL-4 infranormally upregulated CD23 on highly purified B-CLLs both at the protein and at the molecular levels. However, co-stimulation of CLL PBMC with phytohemagglutinin (PHA) and IL-4 strongly upregulated CD23 on B-CLLs, reconstituting the high level of CD23 expression observed in vivo. We next attempted to relate B-CLLs to the CD5+ B cell subpopulations present in peripheral blood mononuclear cells (PBMC, n = 3), cord blood mononuclear cells (CBMC, n = 6) and tonsillar lymphocytes (TONS, n = 3) by analysing their co-expression of CD20, CD5 and CD23 Ag and their phenotypic regulation by IL-4. Our results indicated that B-CLLs presented some features in common with the CD23+ umbilical cord blood B cells in as much as, like in B-CLLs; (i) all CD23+ cord blood cells co-expressed CD5 Ag, (ii) freshly isolated CBMC expressed both type A and type B CD23 mRNA, and finally (iii) these cells weakly re-expressed CD23 Ag upon IL-4 stimulation as compared to adult PBMC.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1991

Antiproliferative effect of interleukin-4 in B chronic lymphocytic leukemia.

Recombinant interleukin-4 (IL-4) profoundly inhibits the proliferative response of chronic lymphocytic leukemic B cells (B-CLLs) to recombinant interleukin-2 (IL-2). In the present study, we confirmed and extended these data by showing that IL-4 strongly suppresses the [3H]thymidine incorporation by B-CLLs stimulated by recombinant tumor necrosis factor alpha, recombinant interferon alpha, IL-2, and low molecular weight B cell growth factor in the absence of costimulant. Recombinant interleukin-4 inhibits spontaneous DNA synthesis suggesting that it also interferes with the autocrine proliferation of these cells. Kinetic studies indicate that IL-4 suppresses rather than shifts the peak of cytokine-induced DNA synthesis. Moreover, IL-4 blocks the progression of B-CLLs in or into G1 stage of the cell cycle as shown by the inhibition of cytokine-induced [3H]uridine incorporation. Finally, IL-4 pretreatment of B-CLLs prevents their subsequent proliferative response to the above cytokines, indicating that IL-4 confers to the B-CLLs a state of resistance to numerous stimulatory cytokines. The antiproliferative effects of IL-4 suggest that this lymphokine may have important therapeutic implications for the B-CLL patients.

Cell Cycle↗
PubMed1990

Expression of CD23 antigen and its regulation by IL-4 in chronic lymphocytic leukemia.

In our previous studies, we reported that the sera from CLL patients contain 3 to 500 times more IgE-BFs (or soluble CD23) than the sera from normal individuals (Sarfati M., Bron D., Lagneaux L., Fonteyn C., Frost H. & Delespesse G. (1988) Elevation of IgE-binding factors in serum of patients with B cell-derived chronic lymphocytic leukemia. Blood 71, 94). In the present study, we have investigated some of the mechanisms accounting for this observation. We report that the density of CD23 expression per cell is significantly higher on the B-CLLs than on the control cells, although the proportion of CD23+ B cells is comparable in both groups (70-90% of CD20+ cells express CD23 antigen). We have next examined the influence of IL-4 on the CD23 expression, the proliferation and the differentiation of B-CLLs. The results indicate that IL-4 (i) increases CD23 expression and IgE-BFs production by normal and CLL B cells; (ii) does not promote B-CLLs proliferation or differentiation, neither by itself nor in costimulation with either anti-IgM or PMA; (iii) significantly potentiates PMA-induced IgM and IgE-BFs production by B-CLLs. It is further shown that anti-CD23 Mab does not interfere with B-CLLs proliferation or differentiation. It is concluded that: (i) the excessive production of IgE-BFs in CLL patients results not only from the enlarged pool of CD23+ B cells but also from an over-expression of CD23 on B-CLLs; (ii) CD23 is not constitutively expressed on B-CLLS and it is upregulated by IL-4; and (iii) by contrast to normal B cells, CD23 on B-CLLs may not be associated with the functional LMW-BCGF receptor.

Aged↗
PubMed1978

Combination of attenuated measles vaccine (Schwarz) with meningococcus A and A + C vaccine.

There is an obvious interest in a combined meningococcus-measles vaccine since the two diseases are widespread and serious in Third World countries among children under five years of age. The purpose of our study was to show the safety and effectiveness of such a combined preparation. The study covered 110 children between 8 months and 4 years of age who were followed systematically in a maternal child health center in the Paris area. Only 93 of them were checked before and after the immunization. The serologic titrations by the hemagglutination assay (IHA) for measles, and by radioimmunological assay (RIA) for meningococcus A and C showed that the Schwarz strain measles vaccine combined with meningococcus A or the association A+C does not interfere with the increase of A or C titers. 100% of the children showed a seroconversion equal to or less than 2 micrograms per ml, in the case of meningococcus A, as well as for C, regardless of age. Furthermore, 88% of the subjects showed a titer greater than or equal to 4 micrograms for the meningococcus A and 79% for C. On the other hand, meningococcus A or the association A+C seem to depress measles vaccine activity. Nevertheless, more than 80% of the children tested showed seroconversion when the measles vaccine was combined with meningococcus A, and only 69% when combined with meningococcus A and C.

Age Factors↗
PubMed1978

[Results of preventive rabies vaccination with a concentrated vaccine of the PM/WI38-1503-3M rabies strain cultured on human diploid cells. Preparation of mixed antirabies-antitetanus hyperimmune immunoglobulin by plasmapheresis of blood taken from vaccinated veterinary students].

Many thousands of people in France and abroad have already benefited from preventive rabies vaccination by means of a vaccine obtained from culture on human diploid cells, perfected ten years ago by R. Lang, the Institut Mérieux and the Wistar Institute. In addition to being well tolerated, the serological efficacy of this vaccine is such that 100% of the vaccines observed had a seroconversion after only two injections at an interval of one month. However, a booster dose should be given 6 to 12 months after the first injection, and a further booster 3 to 5 years later or on request in case of known contamination. These boosters, combined with an anti-tetanus booster, induce such high antibody titers--between 10-100 and even 1000 I.U./ml--that it is easy to obtain substantial batches of combined anti-rabies and anti-tetanus immunoglobulin from a small number of volunteers. The complete efficacy of this new vaccine reduces the number of systematic post-vaccinal serologic controls and its innocuity is such that an extended preventive vaccination programme may be carried out, for instance in the case of children living in areas known to be dangerous.

Adult↗
PubMed1977

Endodontic classification.

Clinical and histopathologic findings are mixed in current endodontic classifications. A new system, based on symptomatology, may be more useful in clincial practice. The classifications are vital asymptomatic, hypersensitive dentin, inflamed-reversible, inflamed/dengenerating without area-irreversible, inflamed/degenerating with area-irreversible, necrotic without area, and necrotic with area.

Acute Disease↗