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J F Delfraissy

Publications and source records attributed to J F Delfraissy.

At least 73 records · Page 4Linked to original sources
PubMed1997

Human immunodeficiency virus gp120 inhibits interleukin-12 secretion by human monocytes: an indirect interleukin-10-mediated effect.

Interleukin-12 (IL-12), a cytokine with in vitro and in vivo immunomodulatory effects, is produced mostly by activated monocytes and macrophages. To study the effect of human immunodeficiency virus (HIV) infection on IL-12 production, we investigated the expression of IL-12 at mRNA and protein levels by human monocytes preincubated with HIV-gp120. In these conditions, we show that monocytes have a decreased ability to express IL-12 mRNA subunits and to produce IL-12 p40 and bioactive p70 proteins in response to Staphylococcus aureus strain cowan I (SAC). We showed that in human monocyte cultures, HIV-gp120 induces a significant IL-10 synthesis, which in turn inhibits IL-12 subunits mRNA accumulation and protein secretion after SAC-activation. Similar data were obtained with human macrophages. These results suggest that, during HIV infection, gp120 induces in uninfected monocytes and macrophages IL-10/IL-12 disregulation, which can alter immune response.

HIV Envelope Protein gp120↗
PubMed1997

Acceptability and impact of zidovudine for prevention of mother-to-child human immunodeficiency virus-1 transmission in France.

We studied the propagation and the impact of zidovudine prevention on the human immunodeficiency virus-1 transmission rate from infected mothers to their infants in the French nationwide prospective cohort. Infection was diagnosed in the children on the basis of at least two positive human immunodeficiency virus-1 polymerase chain reaction tests, culture, or both. The transmission rate among treated women was compared with that among untreated women during the same period and with that among women enrolled in the cohort since 1986. The impact of zidovudine was analyzed according to the women's clinical and biologic characteristics, the mode of delivery, and use of zidovudine therapy before the pregnancy. Nearly 90% of women were treated as soon as the second half of 1994. In 1994 and 1995, 80% of mother-child pairs received at least one of the three phases of preventive treatment. Among the 663 mothers enrolled during these 2 years, only six refused the treatment. Zidovudine treatment was associated with a reduction in the transmission rate of nearly two-thirds, from 14% +/- 6% to 5% +/- 2% (p < 0.01). The degree of reduction was not influenced by the maternal CD4+ cell count or p24 antigenemia at delivery. Zidovudine treatment of the mother before the pregnancy considerably reduced the impact of preventive therapy; the transmission rate was significantly higher among pretreated mothers (20% versus 5%, p < 0.01) even after adjusting for maternal CD4+ cell count. Zidovudine prevention is now widely used in France and has had a major impact on the epidemiology of mother-child human immunodeficiency virus transmission. This justifies a policy of offering human immunodeficiency virus screening to all women before or shortly after the diagnosis of pregnancy.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Maternal virus load during pregnancy and mother-to-child transmission of human immunodeficiency virus type 1: the French perinatal cohort studies. SEROGEST Cohort Group.

Virus load in pregnancy and its relation to mother-to-child human immunodeficiency virus (HIV) transmission were studied prospectively. From 1989 to 1994, 320 HIV-infected women from 18 centers had plasma samples stored. Among women not receiving antiretroviral therapy, the polymerase chain reaction RNA level was 3.6 log at delivery, and 15% of women had levels below the detection limit. There was no variation during pregnancy. Women born in sub-Saharan Africa had lower RNA levels, although their CD4 cell distribution did not differ from that in other women. Among 236 evaluable children, 19% +/- 5% were infected. Transmission occurred in 12% of cases (confidence interval, 5%-22%) with <1000 copies/mL versus 29% +/- 10% of those with >10,000 copies/mL (P < .02). Maternal virus load appears strongly related to HIV transmission to the child.

Africa South of the Sahara↗
PubMed1997

Early protective effect of CCR-5 delta 32 heterozygosity on HIV-1 disease progression: relationship with viral load. The SEROCO Study Group.

OBJECTIVE: To determine the influence of heterozygosity for the delta 32 mutant CCR-5 allele on HIV-1 disease progression. DESIGN: HIV-1 disease progression and serum viral load were analysed according to the C-C chemokine receptor (CCR)-5 genotype in 412 Caucasian patients (319 men and 93 women) with a known date of seroconversion, who were enrolled in the SEROCO cohort (median follow-up, 74 months). RESULTS: The frequency of heterozygosity for the mutant allele was 17% and did not differ according to sex or risk factor of HIV infection. Heterozygotes were significantly less likely than patients with two functional alleles to have symptomatic primary infection. Their serum viral load was lower during the 6- to 24-month plateau phase after seroconversion. This difference persisted afterwards, although the rate of decline in CD4+ cells was similar. Kaplan-Meier survival curves showed slower progression to clinical AIDS in heterozygotes during the first 7 years following infection (P < 0.02), the two curves tending to join thereafter (overall log-rank test, P = 0.17). However, the interaction term with time did not reach significance in a Cox model. The overall relative risk of progression was 0.67 (95% confidence interval, 0.38-1.18) and was not influenced by adjustment for age at seroconversion or symptomatic primary infection. After adjustment for early viral load the relative risk was 0.83. Pneumocystis carinii pneumonia and toxoplasmosis were less likely to be the first AIDS-defining illness in heterozygotes than in the other patients (0 versus 24.7% of AIDS cases, P = 0.04), despite similar management. CONCLUSION: Deletion of one CCR-5 gene allele appears to protect against HIV-1 disease progression, mainly during the early years of the infection. Heterozygosity for the deletion leads to persistently lower viral load, and also seems to protect against some opportunistic infections.

AIDS-Related Opportunistic Infections↗
PubMed1996

The course of the SAPHO syndrome during pregnancy.

In this report, we describe a case of a pregnancy in a 29 year old patient suffering from a new syndrome, the SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis). The SAPHO syndrome improved considerably during the course of this pregnancy and treatment with indomethacin ceased during gestation.

Acne Vulgaris↗
PubMed1996

Interleukin-13 inhibits interleukin-2-induced proliferation and protects chronic lymphocytic leukemia B cells from in vitro apoptosis.

Human interleukin-13 (IL-13) acts at different stages of the normal B-cell maturation pathway with a spectrum of biologic activities overlapping those of IL-4. 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. In vitro, B-CLL cells exhibit a spontaneous apoptosis regulated by different cytokines. In this report, we show that IL-13 (10 to 200 ng/mL) acts directly on monoclonal B-CLL cells from 12 patients. (1) IL-13 enhances CD23 expression and induces soluble CD23 secretion by B-CLL cells but does not exhibit a growth factor activity. (2) IL-13 inhibits IL-2 responsiveness of B-CLL cells, activated either with IL-2 alone or through crosslinking of lgs or ligation of CD40 antigen. (3) IL-13 protects B-CLL cells from in vitro spontaneous apoptosis. The effects of IL-13 on neoplasic B cells were slightly less than those of IL-4 and occurred independently of the presence of IL-4. The present observations show that IL-13 may exhibit a negative regulatory effect on neoplasic B cells in contrast with that observed in normal B cells, and suggest that IL-13 could be an important factor in the pathogenesis of CLL by preventing the death of monoclonal B cells. Moreover, B-CLL may be an interesting model to study the regulation of the expression of IL-13 receptor and/or signal transduction pathways.

Aged↗
PubMed1996

Triggering of CD23b antigen by anti-CD23 monoclonal antibodies induces interleukin-10 production by human macrophages.

The aim of this study was to evaluate the capacity of human macrophages to produce interleukin (IL)-10 upon stimulation of membrane CD23. An anti-CD23 monoclonal antibody (mAb) was found to elicit the expression of the specific mRNA for IL-10 in CD23-bearing macrophages, and to induce a time-dependent production of this cytokine with a maximal effect reached after 12 h. Inasmuch as we previously reported that CD23 ligation evoked the generation of nitric oxide and of cAMP, the effect of the Rp diastereoisomer of adenosine 3', 5'-cyclic phosphorothioate (Rp-cAMP, an inhibitor of the cAMP pathway) and of NG-monomethyl-L-arginine (L-NMMA, an inhibitor of the nitric oxide pathway) were evaluated on CD23-induced IL-10 production. In the presence of Rp-cAMP, the CD23-induced production of IL-10 and of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) was totally abrogated, whereas, in the presence of L-NMMA, IL-10 production was enhanced and TNF-alpha production was suppressed. In addition, neutralization of IL-10 with an anti-IL-10 mAb increased both the magnitude and duration of CD23-driven TNF-alpha production. Such an inducing effect was observed with different anti-CD23 mAb (clone 135, MHM6 and 25), indicating that the triggering of the CD23 molecule at the surface of human macrophages induced the generation of IL-10 through a cAMP-dependent mechanism. Concomitantly this generation of IL-10 was down-regulated by nitric oxide, which was also produced after triggering of the CD23 antigen. Taken together these data indicated that human macrophages produced IL-10 after triggering of the CD23 molecule and that this production could regulate the inflammatory state of these cells.

Base Sequence↗
PubMed1996

Interleukin-13 and interleukin-4 act as interleukin-6 inducers in human microglial cells.

The effect of interleukin 4 (IL-4) and IL-13 on IL-6 and IL-1 beta production by human embryonic microglial cells and human peripheral blood monocyte cells (PBMC) was compared. IL-4 or IL-13 increase intra-cellular IL-6 mRNA and IL-6 titres in supernatants of microglial cells whereas they decreased IL-6 production by PBMC tested in the same conditions. IL-4 and IL-13 increased also IL-1 beta production by human microglial cells. Stimulations associating IL-4 or IL-13 and IL-1 beta had an additive effect on IL-6 production by microglial cells, whereas, in the same conditions, an inhibitory effect was observed in PBMC. In contrast, dexamethasone downregulated IL-6 production by microglial cells and PBMC. Finally, IL-1 receptor (IL-1r) type 1 and IL-1r type 2 were detected on human microglial cells but it was demonstrated that IL-13 and IL-4 acted as IL-6 inducers in human microglial cells independently of the IL-1/IL-1r pathway.

Cells, Cultured↗
PubMed1996

Obstetric factors and mother-to-child transmission of human immunodeficiency virus type 1: the French perinatal cohorts. SEROGEST French Pediatric HIV Infection Study Group.

OBJECTIVE: We attempted to determine whether the risk of mother-to-child transmission of human immunodeficiency virus type 1 is related to events in pregnancy, labor, and delivery. STUDY DESIGN: In a prospective multicenter cohort study of human immunodeficiency virus type 1-infected mothers and their children, we studied pregnancy histories, labor (including gestational age, induction, membrane rupture, length of labor, intrapartum procedures, bleeding, infection, antiseptic technique, and antiretroviral therapy), and conditions of delivery. RESULTS: Among 1632 singleton infants, 310 were confirmed infected with human immunodeficiency virus type 1 at age 18 months (19.0% +/- 1.9%). Procedures (in particular, amniocentesis and amnioscopy) and sexually transmitted diseases during pregnancy, preterm delivery, premature membrane rupture, hemorrhage in labor, and bloody amniotic fluid were associated with increased transmission. Transmission was not related to mode of delivery or to the conditions of labor and delivery. CONCLUSIONS: Transmission was not decreased after emergency or elective cesarean section. Most risk factors either were rare or appeared poorly amenable to obstetric management, with the exception of invasive procedures, which should be avoided.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Lack of evidence of HTLV-I/II infection in T CD8 malignant or reactive lymphoproliferative disorders in France: a serological and/or molecular study of 169 cases.

Human T lymphotropic virus type II (HTLV-II), originally isolated in 1982 from a patient with a "T hairy cell leukemia", has not yet been proven to be the causative agent of any specific hematological disease. In order to screen for such an event, and because HTLV-II has a preferential tropism for OKT8 (CD8) T cells (both in vivo and in vitro), we searched for the presence of HTLV-II in lymphoproliferative diseases (LP) of CD8+ T cells. We report a serological and/or molecular study of 169 patients with a T CD8 LP, including 76 patients with malignant or reactive T CD8 LP (34 lymphomas, 27 large granular leukemias, three prolymphocytic leukemias, one hairy cell leukemia, 11 reactive T CD8 LP) and 93 HIV-1+ patients with a T CD8 peripheral lymphocytosis ( > 1500/mm3) from a prospective HIV cohort involving 1264 individuals. In the first series, the 40 sera available were all HTLV-I/II negative, except a 67-year-old French Guyanan man, with a cutaneous large T CD8 cell lymphoma, HTLV-I+. Furthermore, the molecular analysis of the 69 available DNA samples by PCR failed to detect any proviral HTLV-I/II sequences, except for the HTLV-I+ patient. The serological study of the 93 HIV-1+ individuals with CD8 lymphocytosis, showed that three patients were HTLV-I+, but none was HTLV-II+. Thus, in contrast to HTLV-I, whose etiological role in adult T cell leukemia is now well established, there is neither epidemiological nor molecular evidence that prototypic HTLV-II may be etiologically associated specifically with any of the CD8+ T cell LP investigated in this report.

Base Sequence↗
PubMed1995

[Prescription of antiretroviral and prophylactic drugs in HIV diseases: reality of medical practices].

Antiretroviral and prophylactic therapy given to HIV-infected patients attending hospital (DMI 2 data base) was analyzed according to TCD4+ cell count; 19,020 patients were included in the study. Under 200 TCD4+/mm3, more than 80% of the patients received antiviral therapy, most often AZT (45.3%) or ddI (27.2%). Combined treatment was quite low, less than 8%. Although above 500 TCD4+/mm3, 11.6% of patients received AZT, this study showed that antiretroviral therapy followed French recommendations. This was not the case for prophylaxis: a large proportion of patients under 200 TCD4+/mm3 did not received pentamidine aerosol, or cotrimoxazole, or dapsone.

Anti-Infective Agents↗
PubMed1994

Interferon-alpha-mediated prevention of in vitro apoptosis of chronic lymphocytic leukemia B cells: role of bcl-2 and c-myc.

Chronic B lymphocytic leukemia cells (B-CLL), characterized by the accumulation in vivo of long-life span B cells, exhibit spontaneous programmed cell death or apoptosis when cultured in vitro. We show that interferon-alpha (IFN-alpha), although able to decrease in vivo the number of leukemic cells, protects chronic B lymphocytic leukemia cells from in vitro programmed cell death or apoptosis. This inhibition of spontaneous in vitro apoptosis of leukemic B cells was observed after 24-48 hr of culture with 100-1000 U of either Interferon-alpha 2a or 2b. The protective activity was observed in the majority of the patients tested (6 out of 8) independent of the amount of apoptosis observed. Furthermore, in contrast to IL-4, IFN-alpha did not up-regulate the expression of Bcl-2. This suggests that B-CLL cells can be prevented from undergoing apoptosis in vitro by at least two different mechanisms: one, triggered for instance by IL-4, is associated with Bcl-2 production and the second triggered by Interferon-alpha is Bcl-2 independent. To elucidate the pathways mobilized by Interferon-alpha we also studied the regulation of c-myc expression in our experimental system. We found that (i) induction of in vitro B-CLL apoptosis was not associated with up-regulation of c-myc, (ii) c-myc expression as assessed by mRNA and protein determinations was increased after in vitro or in vivo Interferon-alpha stimulation. Additional experiments using c-myc specific oligonucleotides demonstrated that when Interferon-alpha-mediated c-myc expression was decreased by 60%, the in vitro protective effect of Interferon-alpha was not modified. Thus our data show that in contrast to the situation in vivo, Interferon-alpha prevents spontaneous in vitro B-CLL cells apoptosis through a Bcl-2-independent pathway which is probably not related to c-myc up-regulation.

Aged↗