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Biomedical subjects

J F Delfraissy

Publications and source records attributed to J F Delfraissy.

At least 91 records · Page 5Linked to original sources
PubMed1994

Thrombocytopenia in pregnant women infected with human immunodeficiency virus: maternal and neonatal outcome.

OBJECTIVES: Our purpose was to evaluate the prevalence of thrombocytopenia related to human immunodeficiency virus among seropositive pregnant women and its impact on maternal and neonatal outcome. STUDY DESIGN: A retrospective survey of all deliveries of women infected with human immunodeficiency virus in 14 maternity units in France over a 6-year period collected data on mothers who had thrombocytopenia < 100.10(9)/ and their infants. RESULTS: Among 890 women, 29 were thrombocytopenic (3.2%, 95% confidence interval 2.1% to 4.3%). Thrombocytopenia appeared directly related to human immunodeficiency virus infection in 25 of these women. During pregnancy 16 patients were treated for thrombocytopenia with zidovudine, corticosteroids, or high-dose intravenous gamma globulin. Zidovudine was effective in five of seven cases, and intravenous gamma globulin was effective in five of 11 cases. Cesarean sections were performed in 13 of 29 women. Abnormal intrapartum or postpartum bleeding was recorded in five cases. Among 28 infants for whom neonatal platelet counts were available, only one had thrombocytopenia < 100.10(9)/L at birth; he went on to have early-onset acquired immunodeficiency syndrome. CONCLUSIONS: The incidence of fetal or neonatal thrombocytopenia appears low and may not justify invasive sampling or routine cesarean delivery. Therapy with zidovudine or intravenous gamma globulin should be considered for women with severe thrombocytopenia, because of the risk of maternal hemorrhage.

Adult↗
PubMed1994

Effect of age and exposure group on the onset of AIDS in heterosexual and homosexual HIV-infected patients. SEROCO Study Group.

OBJECTIVE: To analyse the influence of age at seroconversion and sexual exposure group on the progression of HIV disease. DESIGN: This multicentre prospective cohort study involved 443 subjects whose date of HIV infection was known to within +/- 1 year. Individuals whose sexual behaviour was exclusively heterosexual after HIV infection constituted the heterosexual group (n = 131). AIDS-free survival was compared with that of men (n = 312) infected through homosexual sex and who continued homosexual activity after HIV infection. They constituted the homosexual group. METHODS: The end-point was the onset of an AIDS-defining illness listed in the 1987 revised Centers for Disease Control and Prevention (CDC) criteria. Using the Kaplan-Meier method, AIDS-free survival curves were plotted for three age categories (< 20, 20-39, > or = 40 years). A Cox model was used to quantify the effect of age and to assess the influence of exposure group on AIDS onset after adjustment for age. Because of the high incidence of Kaposi's sarcoma (KS) among homosexual men, a disease that can be an early AIDS-defining illness, multivariate analysis was performed with and without consideration of the occurrence of KS. RESULTS: Patients aged > or = 40 years at seroconversion progressed more rapidly to AIDS than younger patients (P < 0.006). When age was fitted as a continuous variable and adjusted for exposure group, the relative risk of developing AIDS by any time after seroconversion was 1.34 for a 10-year increase difference [P = 0.03; 95% confidence interval (CI), 1.03-1.77]. After adjustment for age, the relative risk of developing AIDS (CDC criteria) was 2.42 (P = 0.008; 95% CI, 1.18-4.97) among the homosexual men (AIDS cases, n = 56). All cases of KS (n = 19) involved the homosexual group. Excluding KS as a first manifestation of AIDS, homosexual or bisexual subjects had a risk of AIDS of 1.92 (P = 0.07; 95% CI, 0.92-4.03) compared with heterosexual subjects. CONCLUSIONS: The risk of AIDS increases with age at seroconversion. The more rapid progression towards AIDS in the homosexual group than in the heterosexual group persisted after adjustment for age. Further studies are required to determine the possible role of repeated exposure to HIV or other pathogens acquired sexually.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Staphylococcal superantigens activate HIV-1 replication in naturally infected monocytes.

OBJECTIVES: To study the effects of microbial superantigens, Staphylococcal exotoxins (SE), on HIV replication in monocytes following binding to and signalling through major histocompatibility complex (MHC) class II molecules. METHODS: We investigated the effects of SE on HIV replication and monokine production in three different in vitro models of monocyte culture: chronically infected monocytic cell line U1, acute infection of normal monocytes by different HIV-1 strains, and naturally-infected monocytes from seropositive patients. p24 antigen, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha production was measured by specific enzyme-linked immunosorbent assay (ELISA). RESULTS: Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 (1-1000 ng/ml) are powerful inducers of HIV-1 expression in U1 cells pretreated with granulocyte macrophage colony stimulating factor. SE induce viral replication in short-term cultures (days 6-21) of monocytes infected in vitro by HIVBa-L, HIVLAI, or naturally infected in vivo. Induction of HIV expression requires direct interactions of SE with MHC class II molecules but not T-cell receptor binding and T-cell-monocyte contact. Anti-TNF-alpha and anti-IL-6 neutralizing monoclonal antibodies inhibit by over 61% SE-induced HIV replication. CONCLUSIONS: Using SE we have linked two important pathways for the regulation of HIV replication in monocytes, namely signalling through MHC class II molecules and monokine production potentially mediated by induction of the pleiotropic cellular transcription factor NF-kappa B. In HIV-infected patients bacterial infections are common and could be an important cofactor in the immunopathogenesis of AIDS by inducing HIV replication in latently infected monocytes. Their prevention might emerge as beneficial in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1993

[Anonymous and free-of-charge centers for screening for HIV infection. Results of 30 months of activity in Public Assistance in Paris hospitals].

The results of 30 months of activity of anonymous and free-of-charge HIV detection centres in Paris hospitals are presented. During this period (April 1988 to December 1990), 15805 subjects were seen. This population accounts for about 11 percent of all French anonymous and free detection centres in 1990, and for 26 percent of the number of subjects consulting in detection centres of the same type. Risk factors could be listed in 8132 consulting subjects: 73 percent were heterosexuals and not drug-addicts; 19.5 percent were homo- or bisexuals; 6 percent were drug-addicts; 0.6 percent were both homosexuals and drug-addicts; 29 percent of the 7806 persons questioned about their use of condoms stated that they used them often or always. A total of 15271 blood samples were taken. The percentage of seropositivity was 4.73 percent with a significant fall from 5.87 percent in 1988 to 4.38 percent in 1990; 23.4 percent of homosexual drug-addicts, 17.6 percent of heterosexual drug-addicts, 9.3 percent of homo- or bisexuals and 1.3 percent of heterosexuals were seropositive. In the seropositive population, 46.4 percent were homo- or bisexuals, 29.8 percent were drug-addicts, 19.7 percent were heterosexuals and 3.7 percent were homosexual drug-addicts. Three subjects had been contaminated by blood transfusion. The percentage of seropositive subjects in our study was superior to the mean found in other anonymous and free detection centres (4.73 percent versus 3 percent in 1990), this probably reflecting the high prevalence of the infection in the Paris region. The seropositive subjects usually belonged to the categories primarily affected by the HIV. The percentage of seropositivity in our drug-addicts (17.6 percent) was much lower than that usually reported in French drug-addicts (30 to 40 percent).

Acquired Immunodeficiency Syndrome↗
PubMed1993

Splenectomy is safe and effective in human immunodeficiency virus-related immune thrombocytopenia.

Sixty-eight patients, followed in a prospective cohort study of 185 human immunodeficiency virus (HIV)-infected patients with severe immune thrombocytopenia (platelets < 50 x 10(9)/L), underwent splenectomy, 2 to 41 months (median: 10 months) after immune thrombocytopenic purpura (ITP) was diagnosed. The mean platelet count increased from 18 x 10(9)/L to 223 x 10(9)/L with a persistent increase in 56 (82%). It also led to a significant increase of the mean CD4 cell count from 475 x 10(6)/L to 725 x 10(6)/L within a mean delay of 10 months. In the whole cohort, with a mean follow-up of 63 months (range, 6 to 126), the 5-year estimated rate for progression to acquired immunodeficiency syndrome (AIDS) was 23% (95% confidence interval [CI], 15% to 31%) and the AIDS-free survival was 69% (95% CI, 61% to 77%). To investigate the potential impact of splenectomy, a Cox's multiple regression model was used; as splenectomy was not randomly assigned, it was incorporated as a time-dependent covariate. After adjustment on the CD4 cell count, no statistically significant differences were observed between the splenectomized and the nonsplenectomized patients: AIDS progression rate (P = 0.23), survival (P = 0.64) and AIDS-free survival (P = 0.72) were not influenced by splenectomy. Splenectomy is both effective and safe in the treatment of severe, refractory ITP associated with HIV infection.

Female↗
PubMed1993

In vitro production of IL-6, IL-1 beta, and tumor necrosis factor-alpha by human embryonic microglial and neural cells.

The abilities of the different cells from human central nervous system (CNS) to produce IL-6, IL-1 beta, and TNF-alpha were tested in vitro using either cultures enriched in human embryonic microglial cells or primary cultures of human embryonic CNS cells. High amounts of IL-6, low amounts of IL-1 beta but no TNF-alpha were detected in supernatants of microglial cells, kept either in FCS-free conditions or in FCS-containing medium. Moreover, IL-6 mRNA was also present in 45 to 55% of microglial cells cultured in the presence of FCS as visualized by in situ hybridization, whereas IL-1 beta mRNA remained undetectable. After prestimulation of microglial cells with LPS or IL-1 alpha, the percentage of cells labeled with an antisense IL-6 mRNA probe increased to 70% and hybridization with an antisense IL-1 beta mRNA probe became detectable. In contrast to this dyscoordinate production of cytokines by microglial cells, human monocytes, freshly isolated from blood and kept in the same culture conditions, produced high levels of the three cytokines tested. In primary cultures of human embryonic CNS cells, IL-6, IL-1 beta, and TNF-alpha were produced mostly or only by microglial cells because no IL-1 beta mRNA or IL-6 mRNA were detected in astrocytes, even after prestimulation with LPS or IL-1 alpha. Finally, IL-1 was the main inducer of IL-6 production because IL-1 alpha, but not LPS, induced a significant increase in IL-6 synthesis in cultures kept in FCS-free medium. However, in presence of FCS, LPS appeared to initiate a cascade reaction involving the production of IL-1 by microglial cells, acting as an autocrine loop to trigger IL-6 synthesis.

Astrocytes↗
PubMed1993

[Treatment failure of preventive zidovudine in maternal fetal transmission of HIV].

The role of zidovudine therapy during pregnancy in women infected with HIV-1 is still controversial. A case of a 40-year-old woman, seropositive for HIV-1 since a blood transfusion in 1984 is reported. She was treated by zidovudine since 1989 because of a CDC stage IIIb. The treatment was continued throughout pregnancy at the dose of 600 mg per day. A cesarean section was performed in the 40th week of amenorrhoea. The newborn weighed 3940 g. Viral culture was negative at birth, but positive at the age of four months. Zidovudine and its glucuronide were measured by high performance liquid chromatography in maternal blood taken by venopuncture, in amniotic fluid and in cord blood. In our case, zidovudine was ineffective in preventing transmission of HIV to the fetus despite of a concentration in cord blood higher than minimal therapeutic concentration in vitro. It must be pointed out that all cases of lack of efficacy of zidovudine were described in patients with CD4-cell count lower than 250 per cubic millimeter.

Adult↗
PubMed1992

HIV induces IL-6 production by human B lymphocytes. Role of IL-4.

In vitro, normal B cells can produce TNF-alpha and IL-6 when activated with a first signal, and cytokines and B lymphocytes from some HIV-infected individuals spontaneously secrete TNF-alpha and IL-6, although the direct involvement of HIV has not been fully explored. In this study, we examined the effects of HIV (purified virus and a recombinant envelope protein) and various IL on TNF-alpha and IL-6 in vitro production by highly purified normal B cells. HIV alone did not induce IL-6 or TNF-alpha production by B cells from healthy subjects. HIV induced IL-6 production (500 to 1500 pg) in the presence of IL-4, with a slight production of TNF-alpha. IL-6 production occurred independently of the presence or absence of TNF-alpha in contrast with Staphylococcus aureus cowan + IL-2-activated B cells. Other IL, particularly IL-2, were unable to induce IL-6 secretion by HIV-activated B cells. In vivo-activated B cells from HIV-infected patients spontaneously produce moderate quantities of IL-6 and TNF-alpha. This secretion was markedly increased by HIV, suggesting that IL-6-secreting B cells contain anti-HIV antibody-producing B cells. However, contrary to normal B cells, IL-6 production by B cells from HIV-infected patients was not further enhanced by IL-4. Then HIV itself is able to induce an autocrine production of IL-6 upon interaction with IL-4, which can contribute to the hypergammaglobulinemia and to the global B cell dysfunction observed in HIV-infected patients.

Antigens, CD↗
PubMed1992

HIV-induced, HIV-specific in vitro antibody response by B-cells from HIV-seropositive individuals.

OBJECTIVE: Recent studies have shown that B-cells from HIV-infected patients can secrete anti-HIV antibodies in vitro and that they represent 20-40% of immunoglobulin (Ig)-secreting B-cells in vivo. This study was designed to investigate the precise role of HIV in this in vitro antibody production. DESIGN AND METHODS: B-cells from HIV-infected patients [asymptomatic, n = 28; symptomatic (AIDS), n = 14], from seronegative adult volunteers (n = 22) and subjects at high risk for HIV infection (n = 15) were cultured in vitro in the presence of pokeweed mitogen, Staphylococcus aureus cowan or HIV, and T-cells or interleukins (IL). Non-specific Ig production and specific anti-HIV antibody (Ab) production were measured by enzyme-linked immunosorbent and Western blot assays. RESULTS: We found that HIV induced a specific response in cultured B-cells from seropositive patients, in contrast with cultured B-cells from uninfected normal individuals. The characteristics of the HIV-induced response differed from those of a spontaneous or a mitogen-induced response. Anti-HIV Ab production was optimal on day 8-10, when B-cells were cultured with recombinant IL-2 and recombinant interferon-alpha in the presence of infectious virus or recombinant gp160 Env protein. The anti-HIV Ab were mainly directed against Env proteins. Interaction of HIV with B-cells involved surface IgG but not CD4 antigen. Autologous CD8+ T-cells had a non-specific inhibitory effect. Both CD5+ and CD5- B-cells produced anti-HIV Ab. No anti-HIV Ab production was observed in B-cells from high-risk HIV-seronegative individuals. CONCLUSION: HIV (infectious virus or gp160) can induce B-cells from infected patients to secrete specific anti-HIV Ab in vitro.

Adult↗
PubMed1992

Perinatal HIV transmission facts and controversies.

In 1992, HIV infection in children is essentially due to vertical or perinatal transmission, i.e. from the mother to the fetus and neonates. This is a particularly serious public-health problem in Africa where the percentage of infected women of child bearing age is as high as 20% in some suburban areas. During the last few years, three important points have been established. (i) In Europe and North America, the rate of perinatal transmission is between 15 and 25% and appears to have remained relatively stable with time in various prospective cohorts. (ii) Considerable efforts have been directed at defining the optimal methods for early diagnosis of HIV infection in the infants. At present viral cultures and gene amplification of HIV DNA by polymerase chain reaction are the most promising procedures for early diagnosis within the first 6 months of life. (iii) Finally, the course of the disease in the infected infant has been well characterised, it takes two main forms--that of an early and severe disease or that of a slowly progressive infection: In addition, follow-up is now sufficient to confirm that children with negative tests at 15 months are indeed uninfected. However, knowledge is lacking in a number of essential areas. These include the exact timing of transmission (in utero, during delivery or post-partum), the relative frequency of transmission during each period, the mechanism(s) involved (particularly the role of the placenta), and, finally, the influence of maternal, fetal and viral factors. Answers must be found rapidly in order to develop preventive therapy, to identify women who may have an increased risk of transmitting the virus, to develop a reliable antenatal diagnostic test and, finally, to be in a better position to inform HIV-seropositive women of the relative risks.

Animals↗
PubMed1991

Placental passage of azathiothymidine (AZT) during the second trimester of pregnancy: study by direct fetal blood sampling under ultrasound.

AZT-therapy during pregnancy is actually contraindicated. Two HIV-positive pregnant women who were due to have an induced abortion in the second trimester of pregnancy, were treated with AZT. Blood samples from mothers and fetuses and amniotic fluid samples were taken simultaneously. AZT crossed the placental barrier in the two patients. AZT and GAZT concentrations from the two fetuses were close to those obtained in the two women and in six non-pregnant volunteers.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Production, specificity and structure of immunoglobulins].

Immunoglobulin is a key factor of the immune response resulting from B-cell activation and associated with T-cell stimulation. Because of its structure, this antibody has a dual function: it specifically recognizes the inducer antigen in the variable region and eliminates it by a constant portion which is responsible for effector properties. Surface immunoglobulin, therefore, is the B-cell antigen receptor; it differs from the T-cell receptor in that it recognizes the antigen unbound to the major istocompatibility complex; binding the antigen results in direct signal transduction first in the cytoplasm, then in the nucleus. This receptor can be secreted in the body: it is made up of circulating immunoglobulins. Human immunoglobulins are divided into 5 classes, each of them with its own response kinetics, distribution and functions. The variability of the antibody response accounts for a genetic organization involving numerous genes which may be associated with each other, or mutate, or recombine during maturation of the lymphocytes. Altogether, this system has a theoretical capacity of response to three hundred million different antigens.

Antibody Specificity↗
PubMed1991

Tumor necrosis factor-alpha inhibits the competence signal delivered by HIV to normal B cells.

Polyclonal B cell activation is commonly observed in HIV-infected patients. The coordinate delivery of a number of signals is required for B cell response. This work was designed to better define the role of HIV in the first steps of normal human B cells activation. We show that the infectious virus or recombinant envelope proteins can render B cells responsive to the growth-promoting effect of several T cell-derived IL, IL-2, IL-4, and low m.w. (12-kDa) BCGF. HIV acts in the absence of monocytes and on different populations of B cells. The competence signal can be provided by recombinant gp160 envelope protein. CD4 molecule is not involved in the interaction of HIV with B cells. In addition, we demonstrate that tumor necrosis factor alpha has no promoting activity when B cells are preactivated by HIV and it can suppress the response of HIV-preactivated B cells to IL-2, IL-4, and 12-kDa BCGF. Thus, the HIV envelope can deliver an early signal to normal B cells and modulate B cell response to physiologic signals. The possible relevance of this phenomenon to the immune defect observed in HIV patients is discussed.

B-Lymphocytes↗
PubMed1991

HIV proteins absent from placentas of 75 HIV-1-positive women studied by immunohistochemistry.

Recent epidemiological and virological data suggest that the incidence of maternofetal transmission of HIV-1 infection is between 20 and 30%. The available evidence points to a possible role of peri- and postnatal contamination, but the isolation of HIV from fetuses shows that transplacental transmission also occurs. We attempted to detect, by means of an immunohistochemical method, HIV proteins in frozen placentas from 75 HIV-1-positive women (30 at term, 45 induced abortions). In addition, in situ hybridization using HIV-specific probes was performed in three cases. Neither HIV proteins nor nucleic acid sequences were detected, but CD4+ mononuclear cells were present in the chorion and villi, regardless of the clinical and biological status of the mother (particularly in the nine cases in which the infants were infected). There are several possible mechanisms involving the placenta in the maternofetal transmission of HIV, including active transport of the HIV-immunoglobulin G complex via Fc receptors on trophoblastic cells, passive transplacental passage of HIV during a viraemic episode, the passage of infected maternal cells, and infection of the placenta itself. The methods we used could not rule out the presence of HIV DNA provirus within the genome of placental cells. In any event, immunohistochemical detection of HIV proteins in the placenta is not a technique suitable for the prenatal diagnosis of HIV infection or for identifying newborns likely to develop HIV infection.

Adult↗