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Biomedical subjects

J F Delfraissy

Publications and source records attributed to J F Delfraissy.

At least 109 records · Page 6Linked to original sources
PubMed1991

Efficacy of long term recombinant interferon-alfa in patients with chronic hepatitis C. A clinical, biological, histological and immunohistological study.

A prospective, non randomized trial was conducted in 22 patients with chronic hepatitis C treated for 6 months with interferon-alfa at the dose of 3 million units three times a week followed by decreasing doses for the following 6 months. Transaminase activity measurements were taken at 2, 6, 12, 18, and 24 months and a liver biopsy was performed at zero and 6 months to assess efficacy. Immunohistochemical study of HLA class I and lymphocyte subsets was performed on the biopsy specimen before and after 6 months of treatment. A complete biological response was observed in 82, 82, 60, 64 and 70 percent of patients at 2, 6, 12, 24 and 36 months, respectively. Four patients relapsed including 2 patients who suddenly stopped taking interferon-alfa. An improvement of histological features was observed in 90 percent of patients for necrosis and in 80 percent of patients for inflammation, with an overall improvement in Knodell's score reaching 85 percent. Immunohistochemical studies showed CD8+ cell infiltration already present in the area of necrosis before treatment. These tests also showed that HLA class I expression by the hepatocyte membranes was increased at 6 months and was identical in patients with or without histological improvement.

Adult↗
PubMed1991

[Pulmonary arterial hypertension and systemic diseases].

Certain system diseases which include vascular involvement may be accompanied by pulmonary artery hypertension (PAHT). This chiefly concerns connective tissue disorders, notably scleroderma, CREST syndrome and mixed connective tissue disease and, to a lesser extent, systemic lupus erythematosus. The onset of PAHT in relation to vasculitis of the great vessels or necrosing angeitis is rare. It may result from pulmonary artery vasoconstriction of hypoxic origin during diffuse interstitial pulmonary fibrosis, a thrombo-embolic mechanism, a vasomotor phenomenon equivalent at pulmonary level to Raynaud's syndrome, and above all from pulmonary vasculitis, the commonest mechanism. The incidence of PAHT is such connective tissue disease is probably underestimated since it is a complication often unrecognised clinically. It is a major cause of death in such conditions, certain of which nevertheless enjoy a benign reputation. With the exception of rare cases of favourable outcomes under the influence of corticosteroids and immunosuppressants in cases of mixed connective tissue disease, no treatment has in fact been shown to be effective in terms of survival.

Connective Tissue Diseases↗
PubMed1990

Pharmacokinetics of zidovudine in patients with liver cirrhosis.

The pharmacokinetics of zidovudine (azidothymidine, AZT) was investigated after oral administration (200 mg) in 14 human immunodeficiency virus seronegative patients with liver cirrhosis. They were divided in three groups according to the severity of the liver disease quantitated by the Child-Pugh score. Plasma and urine concentrations of zidovudine and its glucuronidated metabolite (GAZT) were measured simultaneously by HPLC assay. Findings were compared with those previously measured in six healthy volunteers. As a consequence of a marked drop in oral clearance (10 +/- 4 versus 38 +/- 15 ml/min/kg), zidovudine concentrations, half-life, and mean residence time were increased in patients with cirrhosis. No difference could be established between the three groups. The reason for such a decrease in oral clearance of zidovudine was the reduction in the GAZT formation clearance (236 +/- 73 versus 1540 +/- 540 ml/min); this led to a decrease in the AUC ratio of GAZT and zidovudine (1.3 +/- 0.6 versus 4.6 +/- 0.7), which was directly related to the severity of the cirrhosis. In patients, as in volunteers, formation of GAZT rate limits its elimination. To avoid important cumulation of zidovudine after repeated dosing in patients with acquired immunodeficiency syndrome who have hepatic impairment, a dosage adjustment could be proposed.

Adult↗
PubMed1990

Production of interleukins in human immunodeficiency virus-1-replicating lymph nodes.

To document the in vivo interactions occurring between the immune system and HIV replicating cells, we analyzed using in situ hybridization the production of IL-1 beta, IL-6, IL-2, and INF-gamma in eight hyperplastic lymph nodes from HIV-1 infected patients. Numerous IL-1 beta- and IL-6-producing cells associated in clusters were detected in sinuses. Few individual IL-1 beta- and IL-6-producing cells were present in interfollicular and follicular areas. IL-2- and INF-gamma-producing cells were observed in all lymph node compartments, with a selective enrichment in germinal centers. The amount and distribution of IL-1 beta, IL-6-, and IL-2-producing cells in HIV lymph nodes were not different from those found in six HIV unrelated hyperplastic lymph nodes. In contrast, a higher level of INF-gamma production was observed in HIV-1 lymph nodes. The CD8+ cells that accumulate in germinal centers of HIV lymph nodes (and not in non-HIV germinal centers) were actively involved in this INF-gamma production. INF-gamma synthesizing cells were in direct contact with cells containing HIV core antigens and HIV RNA. Thus a high INF-gamma production may characterize anti-HIV T cell immune response, potentially contributing to control of viral spreading as well as to the development of follicle lysis.

Adult↗
PubMed1990

Syncytium induction by fresh HIV isolates: quantitative analysis using a transactivation beta-gal assay.

We used a quantitative bioassay (the beta-gal assay) to visualize and quantify syncytium induction by fresh HIV isolates. This bioassay is based on the transactivation by tat of a chimeric gene comprising an HIV-1 long terminal repeat (LTR) fused to a modified lacZ gene of Escherichia coli. The chimeric gene encodes a beta-galactosidase which is translocated to the nucleus. It allows the enzymatic staining of all nuclei from HIV-induced syncytia. Using this unequivocal assay (the beta-gal assay), we could assess the syncytium-inducing properties of fresh HIV isolates after only 4 days of coculture of patient lymphocytes with activated normal lymphocytes. Syncytium-inducing HIV isolates were detected in 11 out of 40 seropositive patients studied. They were isolated mainly from AIDS patients: eight out of 17 grade IV (according to Centers for Disease Control criteria) patients were infected with syncytium-inducing strains. However, of 23 grade II and III patients tested, syncytium-inducing HIV strains were isolated from three cases. These three patients displayed no detectable p24 antigenaemia and had a CD4+ cell count of greater than 300 cells/microliter. The in vitro replication rate of HIV grown from 36 patient blood samples was then examined by sequential p24 antigen measurements in coculture supernatants. The 10 samples leading to syncytium formation also exhibited the highest replication rate. The possibility of unequivocally detecting syncytium-inducing strains after only a few days of coculture will make this detection routine and rapid. In addition, the limited period of amplification required is a significant advantage as it minimizes the emergence of HIV variants selected during long-term in vitro cultures.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Regulation of human B cell activation and antibody production by non-major histocompatibility complex-restricted cytotoxic T lymphocytes.

To determine whether non-major histocompatibility complex-restricted cytotoxic human T lymphocytes (NrCTL) are involved in the regulation of antibody response, we studied the effect of a CD3+, T cell receptor (TcR)-alpha/beta+, NKH1+ clone named JT9 on B cell proliferation and differentiation. It was found that low amounts of JT9 clone (5%) profoundly inhibited (greater than 80%) in vitro specific anti-trinitrophenyl primary antibody response. This inhibition did not need the presence of autologous T cells and took place at the induction phase of the antibody response. JT9 clone had no effect on resting B cells but enhanced proliferation of anti-mu-stimulated B cells. Respective involvements of cell to cell interaction, cytotoxicity and lymphokines were investigated. (a) The effect of monoclonal antibodies (mAb) inhibiting cytotoxic properties of JT9 clone, i.e. an anti-clonotypic structure mAb and a mAb directed against a target cell antigen similar to 4F2, were studied. These mAb did not reverse the effects of JT9 on B cell activation and differentiation. Thus, these contrasting effects of JT9 clone on B cell response did not seem to involve an interaction of JT9 clone TcR with its target or, further, cytotoxic properties for which this clone had been characterized. (b) Supernatant of JT9 clone stimulated by cross-linking of TcR complex, in the absence of interleukin 2, exerted a proliferative effect on anti-mu-stimulated B cells but not on resting B cells. These findings suggest that JT9 clone could secrete a B cell growth factor-like activity and that NrCTL cells may play an important role in the regulation of antibody response.

Antibody Formation↗
PubMed1989

Extracellular but not intracellular calcium mobilization is required for Epstein-Barr virus-containing supernatant-induced B cell activation.

Changes in intracytosolic free calcium concentration ([Ca2+]i) are though to be an important trigger for the initiation of the cellular events culminating in B cell activation. After exposure of human B lymphocytes loaded with the fluorescent indicator quin-2 to the Epstein-Barr virus (EBV)-containing supernatant of B95-8 cell line, a rise in [Ca2+]i is observed. To determine the respective contribution of the intra- and extracellular Ca2+ pools in EBV-induced B cell activation, the pharmacologic modulation of these processes was investigated using an intracellular calcium chelator, 1,2-bis(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic (BAPTA) or the calcium channel blocking drugs. When the extracellular Ca2+ contribution was minimized in the presence of calcium channel-blocking drugs or incubation of the cells in Ca2+-free medium, the EBV-induced human B cell activation was fully inhibited. When the calcium channel-blocking drugs, either verapamil or diltiazem, were withdrawn or when exogenous Ca2+ was added to the Ca2+-free medium, EBV-induced B cell activation was noted, demonstrating the reversibility of the inhibition. On the contrary, when the intracellular Ca2+ contribution was reduced after loading the cell with BAPTA, no alteration of the EBV-induced B cell activation was observed. Thus, the EBV-induced rise of [Ca2+]i required in the activation of human B cells appears to be essentially related to the entry of extracellular Ca2+ and not to the release of Ca2+ from internal stores.

B-Lymphocytes↗
PubMed1989

HIV-associated endometritis.

Using immunohistochemical staining, in situ hybridization and a combination of both, we demonstrate here the replication of HIV in the endometrial stroma. Infected cells do not belong to the T-lymphocyte lineage but rather to a monocyte-macrophage cell type. This report suggests a possible relationship between HIV infection and endometritis. Moreover, HIV replication in endometrial tissues could play a role in heterosexual and materno-fetal transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Human immunodeficiency virus-associated thrombocytopenia in infants.

Severe thrombocytopenia was the initial manifestation of human immunodeficiency virus infections in 5 infants under 15 months of age. In only 2/5 cases maternal seropositivity was previously known while in the other 3 it was discovered after onset of the infants' thrombocytopenia. One infant died, due to intracranial hemorrhage, and the other 4 developed to disease stage IV. Human immunodeficiency virus infection must be considered in the diagnosis of thrombocytopenia.

Child, Preschool↗
PubMed1988

Activation and infection of B cells by Epstein-Barr virus. Role of calcium mobilization and of protein kinase C translocation.

Both the activation and the transformation of human B cells by EBV were inhibited by either the Ca2+ channel blocking agent verapamil or the combination of theophylline and dibutyryl cAMP: the day 4 and day 20 peaks of [3H]TdR incorporation were abolished; the EBNA marker was not expressed by day 10; lymphoblastoid cell lines did not arise. Short term incubation of B cells with EBV or verapamil showed that the effect of verapamil was reversible and took place early in the interaction between EBV and B cells. The effect of EBV on the early metabolic events of B cell response was thus examined in the presence and in the absence of the drugs. Compared to anti-mu stimulation, supernatant of the transforming B95-8 strain as well as that of the non-transforming P3HR1 strain induced a drug sensitive increase of the free cytosolic Ca2+ concentration. This increase was associated with a protein kinase C translocation from the cytosol to a membrane bound compartment. Moreover, B95-8 supernatant induced phosphatidyl inositol metabolism by human B cells but at least four times less than that induced by anti-mu antibody. These metabolic events induced by EBV were significantly inhibited by anti-CD21 antibodies whereas anti-mu induced metabolic events were not. The infection of EBV negative Ramos cell line was prevented by verapamil or by theophylline + dibutyryl cAMP. Verapamil did not modify the density of EBV receptors but negatively interfered with the penetration of the virus into B cells. Thus B cell activation through the EBV receptor and virus penetration share a common metabolic pathway which is also used for transduction of the signal delivered through the membrane Ig.

Antibodies, Anti-Idiotypic↗
PubMed1988

Role of the LFA3-CD2 interaction in human specific B cell differentiation.

We examined the role of the lymphocyte function-associated (LFA)3 molecule in human B cell response. A mAb to this molecule did not influence B cell proliferation induced by anti-mu antibody and IL. In contrast, the same mAb inhibited the specific T-dependent B cell response induced by a particulate Ag. In the same line, two anti-CD2 mAb (directed toward the T11-1 and T11-2 epitopes) inhibited this response, whether used alone or in association. These inhibitions took place at an early stage of the response, and anti-LFA3 and anti-CD2 mAb acted on B cells and T cells, respectively. In contrast, when T cell help was provided by exogenous IL-2, the B cell response was resistant to the inhibitory effect of anti-LFA3 mAb. Taken together, these results indicate that the LFA3-CD2 pair play a major role in the direct T-B interaction required for T cell help.

Animals↗
PubMed1988

Positive effects of interferon-alpha on B cell-type chronic lymphocytic leukemia proliferative response.

We studied the effect of recombinant interferon-alpha (IFN-alpha) on the proliferative response of normal human B cells and of lymphocytes from 10 patients with B cell-type chronic lymphocytic leukemia. We show that IFN-alpha, which has no effect on B cell proliferation when used alone, can synergize with anti-mu antibody and can support DNA synthesis by anti-mu activated B cells. This was observed with normal B cells and in 4 of 10 patients with B cell-type chronic lymphocytic leukemia. These four patients were all responders to B cell growth factor (BCGF), whereas the responsiveness to IFN-alpha was not correlated with that of IL-2. The positive functional relationship between IFN-alpha and BCGF in these patients is emphasized by the synergistic effect of these two factors in two of these patients, and the lack of inhibition of BCGF response by even supraoptimal concentrations of IFN-alpha. Among the subgroup of patients unable to respond to IFN-alpha, a synergy between IFN-alpha and IL-2 could be observed.

Adult↗
PubMed1988

Interferon-alpha can synergize with interleukin 2 for human in vitro antibody response.

We tested the effect of interferon (IFN)-alpha on the specific anti-2,4,6-trinitrophenyl (TNP) response induced by TNP-conjugated polyacrylamide beads in cultures of purified human B cells. IFN-alpha alone had no effect. Interleukin 2 (IL2) alone had a restorative effect which could be considerably (10X) enhanced by IFN-alpha. This reflected a true synergy most apparent with IL2 concentrations of 10 U/ml and IFN-alpha concentrations of 10(3)-10(5) U/ml. The highest concentrations of IFN-alpha were not inhibitory. In contrast, IFN-alpha did not enhance the effect of an IL2-free T cell-derived supernatant able to support the B cell differentiation. Sequential incubations showed that IFN-alpha acted earlier than IL2 on B cell response. The effect of IFN-alpha was dependent on an efficient interaction between IL2 and its receptor which could be inhibited by a monoclonal antibody toward the CD25 antigen. Thus, IFN-alpha can positively interact with a well defined interleukin, IL2, at a pre or post receptor level to potentiate antibody response.

Antibody Formation↗
PubMed1988

[Hepatic involvement in HIV 1 virus infection].

One hundred consecutive patients with serum antibodies against HIV 1 were evaluated for the prevalence and the type of liver injury. According to the CDC classification, 16 patients belonged to group II (asymptomatic patients), 47 to group III (persistent generalized lymphadenopathy) and 37 to group IV (11 constitutional disease, 19 secondary infectious diseases, 5 secondary cancers, one chronic lymphoid interstitial pneumonitis and one visceral leishmaniasis). Liver histology was studied in 32 patients. Clinical, biological and histologic abnormalities were assessed according to the clinical group and to the number of T4 lymphocytes. The prevalence of HBV infection was determined by HBV DNA and monoclonal antibodies. Clinical hepatic abnormalities were rare (13 p. 100) and no difference was found between groups. Transaminases or GGT activities were elevated in 60 p. 100 of all cases. Serum GGT activity was higher and serum albumin lower in patients in group IV. HBV infection markers were less frequently found in patients with opportunistic infection (74 p. 100) than in asymptomatic patients (100 p. 100; p less than 0.05). Prevalence of serum HBsAg detected by poly- or monoclonal antibodies was very high (29 p. 100) in all clinical groups. Prevalence of serum HBsAg detected only by monoclonal antibodies (10 p. 100) suggest infection of these patients by an HBV variant. Of the 32 patients undergoing liver histology, only 5 (16 p. 100) had signs of activity. There was no association between clinical or histologic signs and the number of T4 lymphocytes per ml. Alkaline phosphatase, ASAT and GGT activities were higher and serum albumin lower in patients with less than 200 T4 lymphocytes per ml.

Adolescent↗