Search PubMed⌕ Search

Biomedical subjects

B Dupont

Publications and source records attributed to B Dupont.

At least 109 records · Page 6Linked to original sources
PubMed1996

The development of cellular immunity to Epstein-Barr virus after allogeneic bone marrow transplantation.

Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) is a potentially lethal complication during the first 6 months after allogeneic bone marrow transplantation (BMT). To determine whether deficiencies of EBV-specific cellular immunity contribute to EBV-LPD susceptibility and distinguish patients at risk, we performed limiting dilution analysis to quantify anti-EBV cytotoxic T-lymphocyte precursor (CTLp) frequencies in 26 recipients of unmodified or T-cell-depleted (TCD) grafts from EBV-seropositive donors. At 3 months post-BMT (n = 26), only five patients had EBV CTLp frequencies in the range of seropositive normal controls, irrespective of the type of transplant administered. By 6 months post-BMT, 9 of 13 patients tested had EBV CTLp frequencies within the normal range. The time period in which these patients had deficient cellular immunity to EBV corresponds to the period in which we have observed EBV-LPD in most prior patients. One patient with a low EBV CTLp frequency at 4 months post-BMT developed an EBV-LPD. Within 2 weeks of receiving an infusion of donor peripheral blood mononuclear cells (PBMC) providing less than 1,200 EBV-specific cytotoxic T-cell precursors, populations of EBV-specific CTL in the circulation were restored to levels detected in normal seropositive adults. Concurrently, the patient achieved a regression of the EBV-LPD, which has been sustained without further therapy. These studies indicate that recipients of both unmodified and TCD marrow grafts have profound deficiencies of EBV-specific T cell-mediated immunity early posttransplant, and that the period of risk for EBV-LPD closely corresponds to this interval of severe deficiency. Treatment of one patient with EBV-LPD with marrow donor-derived PBMC induced a rapid expansion of EBV-specific cytotoxic T-cell populations that occurred contemporaneously with the clinical regression of disease.

Adolescent↗
PubMed1996

AIDS-associated cytomegalovirus infection mimicking central nervous system tumors: a diagnostic challenge.

We reviewed cases of cytomegalovirus (CMV) infection of the central nervous system (CNS) that initially masqueraded as tumors in 37 of 543 consecutive patients infected with human immunodeficiency virus (HIV) and CMV who were seen at the Pasteur Institute Hospital and Saint-Louis Hospital (Paris) between 1992 and 1994. We detail the clinical features of three patients who presented with ring-enhanced space-occupying lesions mimicking CNS tumors. They were all profoundly immunodepressed (mean CD4 cell count, 13/mm3). Magnetic resonance imaging (MRI) showed enlargement of the spinal cord in one case, consistent with a space-occupying lesion and showing gadolinium enhancement; in the other two cases, ring-enhanced mass lesions were seen in the cerebral hemispheres. In all three cases marked edema and a mass effect were present. Image-guided stereotactic biopsies confirmed the diagnosis of CMV infection. The three patients' conditions improved with specific therapy. MRI showed enhanced focal intraparenchymal lesions consistent with marked focal necrosis, probably related to the severity of immunodepression, as HIV infection had been diagnosed several years previously. CMV infection should be considered as a cause of ring-enhanced space-occupying mass lesions in patients with HIV-1 infection. Earlier identification of these unusual tumorlike forms of CMV infection by means of MRI should result in improved outcome.

AIDS-Related Opportunistic Infections↗
PubMed1996

Comparison of the efficacy of amphotericin B and fluconazole in the treatment of cryptococcosis in human immunodeficiency virus-negative patients: retrospective analysis of 83 cases. French Cryptococcosis Study Group.

We retrospectively analyzed clinical outcome of meningeal and extrameningeal cryptococcosis in HIV-negative patients treated with amphotericin B (43 patients) or fluconazole (40 patients). Amphotericin B and fluconazole were prescribed equally to patients with neoplastic diseases and no risk factor, but organ transplant recipients and patients with other diseases were mostly given fluconazole and amphotericin B, respectively. Patients with more severe infections (i.e., meningitis, neurological disorders, or higher levels of antigen in cerebrospinal fluid) were more frequently treated with amphotericin B. A cure rate of > 70% was achieved regardless of the initial treatment and the severity of the infection. A Cox regression analysis showed that age of > 60 years, neoplastic disease, abnormal mental status, disseminated infection at the time of diagnosis, and therapeutic failure were independent predictors of death. Although fluconazole appears to be as effective as amphotericin B, only a prospective multicenter study will determine the best treatment regimen for patients with cryptococcal meningitis who do not have AIDS.

Adult↗
PubMed1996

Spondylodiskitis due to Candida albicans: report of two patients who were successfully treated with fluconazole and review of the literature.

We report the cases of two patients with spondylodiskitis due to Candida albicans who were successfully treated with fluconazole. On the basis of findings from these cases and a review of 52 mycologically proven cases in the literature, we describe the main characteristics of candidal spondylodiskitis. In 60% of the cases, candidal spondylodiskitis was a late complication of candidemia (mean delay, 5.2 months) it was determined to be a complication on the basis of the results of previously positive blood cultures (19 cases), and it was presumed to be a complication in iv drug addicts (12 cases). As spondylodiskitis can be a late complication of candidemia, all episodes of candidemia should be treated with systemic antifungal agents. Clinical and radiological signs of candidal spondylodiskitis were nonspecific. Any bone or joint symptoms in a patient who has had candidemia should be considered to be of fungal origin at the time of presentation. The definitive diagnosis of candidal spondylodiskitis was made on the basis of the results of percutaneous puncture in 26 of 30 cases. The overall prognosis for patients with candidal spondylodiskitis was good, with the full recovery rate ranging from 67% to 100%. The preliminary results of treating candidal spondylodiskitis with triazole derivatives, particularly fluconazole, were satisfactory; there was excellent tolerance of this drug.

Antifungal Agents↗
PubMed1996

Epidemiology of cryptococcosis in France: a 9-year survey (1985-1993). French Cryptococcosis Study Group.

We analyzed the data collected during a nationwide survey of cryptococcosis (1985-1993). We first checked the quality of the survey. The stability of its completeness (approximately 50%) and its representativity were assessed by the capture-recapture method after we cross-checked our data on cryptococcosis (as a presenting manifestation of AIDS) against those of the national registry of AIDS. Of the 1,057 cases of cryptococcosis (1,013 patients), 827 (86%) involved patients with AIDS. The increasing number of cases of human immunodeficiency virus (HIV)-related cryptococcosis over time paralleled the AIDS epidemic except for a higher male-to-female ratio. Malignancies (32%), organ transplantation (19%), and corticosteroid therapy (33%) were the main predisposing conditions in 163 patients without AIDS. Cryptococcal meningitis more frequently occurred in patients with AIDS than in HIV-negative patients (P < 10(-6)). Among the 413 isolates available for serotyping, 410 were Cryptococcus neoformans variety neoformans (including 20.5% of serotype D). Three isolates of the variety gattii (serotype B) were recovered from patients without AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1996

Individual and environmental factors associated with infection due to Cryptococcus neoformans serotype D. French Cryptococcosis Study Group.

Differences between the two varieties of Cryptococcus neoformans with regard to geographic distribution, epidemiology, and even pathogenicity have been described. None between C. neoformans variety neoformans serotypes A and D have been reported. We reviewed 452 cases of cryptococcosis diagnosed in France, where serotype D is responsible for 21% of the infections. Univariate analysis showed that the frequency of serotype D infections was significantly higher among patients > 60 years of age, those born in Europe, those receiving corticosteroid therapy, and those who had skin lesions. In the multivariate analysis, the risk of serotype D infection was significantly higher for patients with skin lesions, those receiving corticosteroid therapy, and those living in certain regions in France. It was significantly lower for patients with meningitis those coming from Africa, and females. Among the 350 human immunodeficiency virus-infected patients, the risk was significantly higher for those > 60 years old, those who were intravenous drug abusers, and those with skin lesions. The risk was significantly lower for patients from Africa and in cases of meningitis. These results suggest that individual and environmental factors can be associated with the serotype of the infecting strain of C. neoformans.

AIDS-Related Opportunistic Infections↗
PubMed1996

CD2 signaling in T cells involves tyrosine phosphorylation and activation of the Tec family kinase, EMT/ITK/TSK.

Ligation of the CD2 cell surface glycoprotein expressed on T lymphocytes and NK cells induces protein tyrosine phosphorylation and activation of the Src kinases, LCK and FYN. We show here that in Jurkat T leukemia cells and in peripheral blood T cells, CD2 stimulation also leads to tyrosine phosphorylation and activation of the Tec family kinase, EMT/ITK/TSK. Activation of EMT by CD2 was induced by mitogenic pairs of CD2 mAb, certain single CD2 mAb followed by secondary antibody cross-linking, and CD58-bearing sheep red blood cells. With the use of different Jurkat cell mutants it was demonstrated that CD2-mediated activation of EMT required expression of LCK, but not require surface expression of the CD3 zeta chain. Receptor-mediated activation of LCK does not in itself lead to activation of this Tec kinase since induction of LCK by ligation of CD4 or CD5 did not result in activation of EMT. The activation of EMT during CD2 signaling suggests an important role for this kinase in CD2 co-stimulation of T cell responses.

CD2 Antigens↗
PubMed1996

Acute retinal necrosis in the course of AIDS: study of 26 cases.

OBJECTIVE: To report 26 cases of acute retinal necrosis (ARN) in HIV-infected patients, to compare these data with the literature and to discuss the clinical spectrum of ARN during HIV infection. DESIGN AND SETTING: Twenty-six HIV-infected patients with ARN, collected from five ophthalmology departments in Paris (France) between 1985 and 1993, were analysed retrospectively. PATIENTS: Twenty-eight patients were enrolled; two were lost of follow-up. Diagnosis of ARN was established on the following criteria: (1) inflammation of the anterior segment and the characteristic triad, and (2) peripheral circular necrosis with centripetal progression toward the posterior pole associated with occlusive periarteritis and inflammation of the vitreous. RESULTS: ARN is a late event in the course of immunosuppression (CD4+ lymphocyte count < 100 x 10(6)/l). The most frequent presenting syndrome is a decrease of visual acuity, but signs related to a retrobulbar optic neuritis may also be present. In 60-90% of cases, vesicular viral eruption, usually shingles, precedes the onset of ARN by several days. Occasionally, neurological impairment is also present. Progression to blindness occurs in 76-85% of cases, bilaterally in 59%, and is usually induced by retinal detachment. This study and literature data suggest that varicella zoster virus (VZV) is directly implicated in the onset of ARN. At present, the most efficient therapeutic schedule is unknown. CONCLUSION: ARN is a rare and serious disease in AIDS patients. It is often associated with VZV infection. There is no preventive or curative efficient treatment. ARN might be considered as another opportunistic infection because of its rapid clinical evolution and severe prognosis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Large-scale DRB and DQB1 oligonucleotide typing for the NMDP registry: progress report from year 2.

DNA typing of HLA class II alleles of the DRB1/3/4/5 and DQB1 loci using sequence-specific oligonucleotide probes and polymerase chain reaction amplified DNA has been used for the large-scale typing of donors for the National Marrow Donor Program unrelated donor registry. The results of quality control analysis for the second year of the project (10/1/939/30/94) show the typing continues to be highly accurate, specific, and reliable. The average percent of correctly classified HLA oligotypes (groups of alleles defined by a hybridization pattern with a panel of sequence-specific oligonucleotide probes) based on 9,244 DRB1 and 7,244 DQB1 assignments was 99.8% (range 99.4%100.0%) for DRB1/DRB3/DRB4/DRB5 and 99.8% (range 99.6%100.0%) for DQB1. This level of accuracy is particularly remarkable because the 4,636 DRB quality control samples were tested blindly and could not be distinguished from 57,580 donor samples tested at the same time by the laboratories.

Alleles↗
PubMed1996

Comparison of HLA-A antigen typing by serology with two polymerase chain reaction based DNA typing methods: implications for proficiency testing.

Serology has been routinely used for class I HLA typing for the selection of donors for allotransplantation. However, serology is not adequate for the assignment of all class I specificities especially when testing non-Caucasians subjects and it is necessary to adopt new strategies for routine testing. At the present time the extent of incorrect serologic HLA-A assignments in clinical testing is not known. The polymerase chain reaction (PCR) based techniques have become useful standard clinical typing methods of HLA class II alleles but most laboratories still use serology for class I typing. In this report we have compared two PCR based techniques, PCR amplification with sequence-specific primers (PCR-SSP) and PCR amplification and subsequent hybridization with sequence-specific oligonucleotide probes (PCR-SSOP), for the assignment of HLA-A specificities in 56 blood samples from patients and families serologically typed for HLA-A. This side-by-side comparison of PCR methods showed 100% correlation between them. However, serology showed 7.1% misassignments and, in an additional panel of 19 cells where serology produced equivocal results, the PCR-SSP and SSOP methods identified the correct HLA-A specificity. Our results emphasize the need to complement routine serologic testing of HLA specificities with a small number of primers designed to test HLA-A34, A36, A43, A66, A74 and A80, that are not detected with high precision by serology. We concluded that the PCR-SSP and -SSOP methods can be used in routine HLA-A typing of patients and donors for transplantation with a greater precision than serology.

HLA-A Antigens↗
PubMed1996

Phosphorylation of each of the distal three tyrosines of the CD28 cytoplasmic tail is required for CD28-induced T cell IL-2 secretion.

Signaling by the CD28 T cell costimulatory receptor is known to involve recruitment and activation of phosphatidylinositol 3-kinase (PI3-kinase) which is dependent upon phosphorylation of tyrosine 173 of the CD28 cytoplasmic tail, present in a YMNM motif. However, whether this phosphorylation is required for CD28 costimulation and whether or not phosphorylation of any of the other three tyrosines of the CD28 cytoplasmic tail (tyrosines 188, 191 and 200) is also important for CD28 induced responses is unclear. To address this we examined the ability of chimeric receptors, consisting of the extracellular plus transmembrane membrane domain of human CD8 alpha linked to different mutated human CD28 cytoplasmic tails, to induce IL-2 secretion in Jurkat T leukemia cells in the presence of PMA and ionomycin. A receptor in which tyrosine 173 of the CD28 tail was mutated to phenylalanine was able to induce IL-2. By contrast, receptors which contained single tyrosine 188, 191 or 200 to phenylalanine substitutions were unable to induce IL-2. These results imply that in this system phosphorylation of tyrosine 173 and hence activation of PI3-kinase is not required for CD28 induced IL-2 secretion. Further, they imply that phosphorylation of each of tyrosines 188, 191 and 200 is necessary for this response. Despite an apparent requirement for phosphorylation of all three of these tyrosines, however, receptors which contain tyrosine only at positions 191 or 200 and a truncated receptor which does not contain tyrosine 200 induce normal IL-2. These last findings, therefore, illustrate the complexity of CD28 mediated activation signals.

CD28 Antigens↗
PubMed1996

NK cell receptor gene of the KIR family with two IG domains but highest homology to KIR receptors with three IG domains.

The killer cell inhibitory receptors (KIRs) are surface glycoproteins expressed by natural killer (NK) cells and some T cells. They recognize polymorphic human HLA class I molecules. Two families of KIRs have been identified and named p58 and p70. The p58 family of genes encode type I membrane proteins with two extracellular immunoglobulin (Ig) domains, while the p70 genes have three Ig domains. We here report the cloning and characterization of a novel KIR cDNA obtained from tumor cell lines with NK reactivity (YT and NK-92). This gene is also expressed in the normal cell line NK 3.3 and in NK cells obtained from some but not all normal donors. The clone, KIR103AS, has an open reading frame consistent with a KIR with two extracellular Ig domains, a transmembrane region and a 114 amino acid long cytoplasmic domain containing a single src homology 2 (SH2) binding motif. The membrane distal Ig domain of KIR103AS has highest homology with the first Ig domain of p70 KIRs and differs significantly from the first Ig domain of p58 KIRs. The second, membrane proximal Ig domain of KIR103AS has similar and high homology with the membrane proximal Ig domains of both p70 and p58 KIRs. The extracellular domains of KIR103AS therefore share characteristic features with both p70 and p58 genes: the domain structure is identical to p58 KIRs but the sequence homology matches closely with p70 KIRs. The putative transmembrane and cytoplasmic domains are distinctly different from all previously reported KIR cDNAs.

Amino Acid Sequence↗