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Biomedical subjects

M Buisson

Publications and source records attributed to M Buisson.

At least 19 recordsLinked to original sources
PubMed1995

T-cell death by apoptosis in vertically human immunodeficiency virus-infected children coincides with expansion of CD8+/interleukin-2 receptor-/HLA-DR+ T cells: sign of a possible role for herpes viruses as cofactors?

One mechanism proposed to play a role in T-cell depletion in human immunodeficiency virus (HIV) infection is apoptosis (activation-induced cell death). We assessed whether apoptosis is related to activation of T cells in vivo and its possible triggers. DNA was extracted from peripheral blood mononuclear cells (PBMC) taken from 16 vertically HIV-infected children and 9 HIV-negative children born to HIV-positive mothers (controls) and tested by agarose gel electrophoresis for the presence of DNA fragments specific for apoptosis. Signs of apoptosis were found on in vitro culture of PBMC from 12 of 16 HIV-infected children, but not in PBMC from the nine controls. Eleven of the 12 HIV-infected children with apoptosis showed an elevated (> 15%) proportion of CD3+/HLA-DR+ cells. This was due to an increased proportion of CD8+/HLA-DR+ cells, as shown in 7 of 7 further tested patients. In none of the probands an increased (> 5%) proportion of IL-2 receptor expressing CD3+ cells was found. T cells undergoing apoptosis were preferentially of the CD8+ phenotype. Expansion of circulating CD8+/interleukin-2 receptor (IL-2R)-/HLA-DR+ T cells is known to occur during active infection with herpes viruses. To investigate the possible role of herpes viral coinfections for apoptosis in HIV infection, we focused on Epstein-Barr virus (EBV) as an example for a herpes virus usually acquired during childhood. In 10 of 12 patients with apoptosis, we found increased levels of EBV genome in PBMC and/or tissues, indicating active EBV replication. By contrast, no increased burden of EBV was found in the four HIV-infected patients without apoptosis or in the controls. Our data indicate that in children the occurrence of apoptosis in HIV infection is closely related to activation of CD8+ T cells. Furthermore, primoinfection with or reactivation of herpes viruses, such as EBV, may substantially contribute to such T-cell activation and the ensuing apoptosis. Additional studies are warranted to evaluate the contribution of herpes virus-triggered apoptosis to the T-cell loss leading to the acquired immunodeficiency syndrome.

Apoptosis↗
PubMed1995

[Neurologic manifestations of Lyme disease. Apropos of 25 cases].

We studied retrospectively the cases of neurological forms of Lyme disease observed in two internal and two neurological departments from 1986 till 1993. Twenty five cases have been collected among 15 men and ten women whose mean age was 61 years. Tick bites were previously noticed in 11 cases. Erythema chronicum migrans (ECM) was mentioned in 16 cases mostly on lower limbs. The mean time between ECM and the onset of neurological symptoms was less than 1 month in 11 cases, 2 months in three cases, and 6 months in two cases. Neurological abnormalities were often associated in the same patient. Hyperalgic radiculitis (n = 16), mainly noticed in the ECM territory (n = 10) was only sensitive in six cases and associated with motor deficit in ten. Atypical polyradiculoneuritis was achieved in six cases. Clinical (n = 5) or biological (n = 22) meningitis could occur: CSF was clear with pleiocytosis (132 per mm3), mainly lymphocytic, and hyperproteinorachia (1.2 g/l) with normoglycorachia. An increase of the CSF immunoglobulins G with oligoclonal fragmentation was noticed in 11 cases. Cranial neuropathy was frequent: VII (n = 8), VI (n = 2), III, IV, VIII (n = 1). Encephalitis (with white matter demyelination) resolved partially in two cases. Diagnosis was always confirmed by Borrelia burgdorferi serology (indirect immunofluorescence) with a significant increase of the antibodies titer (n = 17) or a CSF titer > 1/4 (n = 11). Syphilitic serology was always negative. All patients were treated with parenteral beta lactamins and four with corticosteroids. Outcome was favorable in 20 patients with incomplete resolution of neurological symptoms in two patients.

Adult↗
PubMed1995

[Invasive pulmonary aspergillosis in neutropenic patients. Analysis of a series of 36 cases: contribution of thoracic scanners and itraconazole].

In neutropenic patients, one way of improving invasive pulmonary aspergillosis (IPA) prognosis is an earlier initiation of the antifungal treatment. We report our experience with 36 cases of IPA in 35 patients with haematological malignancies. When aspergillosis was diagnosed, all but 2 patients were neutropenic (PMN < 500; median duration = 20 days). The most frequent clinical signs were cough (100%), chest pain (78%) and haemoptysis (58%). Before the diagnosis of IPA, Aspergillus antibody test was positive in 60% of cases. A thoracic CT-scan was performed in 23 patients and demonstrated highly suggestive images in 22 cases (96%) with presence of CT halo sign (n = 13) or CT air-crescent sign (n = 9). Moreover, Aspergillus antigen test was positive in 13 of 28 tested patients. IPA diagnosis was determined to be definite in 23 cases and probable or possible in 13 cases. Thirty-five patients were treated: in 3 cases with amphotericin B (2 failures) and in 32 cases with itraconazole (7 failures and 25 successes or improvements). In 7 cases (including 5 emergencies) surgical resection was successfully combined with the medical treatment. In neutropenic patients with fever, we consider that thoracic CT-scan and repeated biological tests (Aspergillus antibody and antigen tests) can be used to establish the diagnosis of aspergillosis. Early treatment with itraconazole and surgical resection appears to improve prognosis.

Adult↗
PubMed1994

[New macrolides].

The macrolides are still widely used in general practice and the new 14- or 15 membered-ring compounds-roxithromycin, clarithromycin, dirithromycin, azithromycin -may offer a new development. Their antibacterial activity is similar to erythromycin but azithromycin is more active against Gram negative strams. Roxythromycin exhibits high serum concentrations; azithromycin and dirithromycin present low serum concentrations but prolonged half-lives allowing a reduction of the duration of treatment particularly for pharyngitis (azithromycin). Macrolides are less useful for otitis and sinusitis treatment since their activity against H. influenzae and S. pneumoniae are weak. The activity against atypical bacteria justify their choice as first line treatment for benign atypical pneumonia of healthy young adults and for sexually transmitted diseases. In AIDS, these compounds are indicated in mycobacteriosis (clarithromycin), bacillary angiomatosis and excavated pneumonia due to Rhodococcus equi. Clinical tolerance is very good, particularly the gastro-intestinal one. The reported drug interactions are those of this class of antibiotics.

Anti-Bacterial Agents↗
PubMed1994

Lack of relationship between the Epstein-Barr virus and the antiperinuclear factor/'perinuclear antigen' system in rheumatoid arthritis.

Our purpose was to evaluate the role of Epstein-Barr virus (EBV) in the production of antiperinuclear factor (APF), a rheumatoid arthritis (RA)-specific marker, and the autoimmunogenicity of 'perinuclear antigens' (PNA) found within the buccal mucosa epithelial cells used as a substrate in the APF assay. Fifty APF-positive and 50 APF-negative sera from RA patients were examined for the presence of antibodies to six different EBV antigens. APF was tested in the serum of 40 patients with acute infectious mononucleosis (IM), 48 PNA-expressing donors and 29 non-PNA-expressing donors. The EBV genome was sought in the saliva and buccal cells of both types of donors. The targeted granules of cells from a PNA-expressing donor were studied by electron-microscopy. The prevalence of anti-EBV antibodies was similar in RA patients with and without APF, whereas the APF-positive sera was elevated in acute IM. The titres of anti-EBV antibodies did not correlate to the expression of PNA in the buccal cells of the donors. There was no relationship between this expression and the presence of the EBV genome in the material obtained from 'positive' donors, relative to 'negative' donors. No virus-like particles could be detected inside the granules by electron microscopy. These results indicate that there are no direct relationships between EBV and the APF/PNA system, although APF was present in a number of patients with IM.

Adult↗
PubMed1994

[Epidemiological, clinical, biological and developmental aspects of leptospirosis: apropos of 30 cases in Aquitaine].

We have studied retrospectively 30 cases of leptospirosis observed in Aquitaine (South West France) from 1980 till 1992. This review was made in three internal and a nephrology department in Bordeaux hospital. Most cases occurred by indirect contact with infected animals or by occupational exposures. Onset was brutal with fever often associated with painful syndrome and sometimes conjunctival suffusion. Jaundice (70%), acute renal failure (67%), meningitis (50%) and hemorrhagic signs (50%) were among the major visceral manifestations. Diagnosis was always confirmed by micro-agglutination test. Leptospira ictero-hemorrhage was the predominant serogroup found. The outcome was favorable in 22 patients; reversible complications were seen in six cases (five acute renal failure with hemodialysis myocarditis and pulmonary edema in two hemodialysed patients, polyradiculoneuritis). Two patients died (acute respiratory failure and meningo-encephalitis with diffuse hemorrhagic syndrome). The characteristic of our series is the high frequency of hepatorenal syndrome due to the importance of our nephrologist recruitment. Furthermore our study confirm the vital prognostic characters of the pulmonary, renal, hemorrhagic and neurologic complications. No absolute relationship was found between the clinical and laboratory findings and the serotype of leptospira. Penicillin remains the treatment of choice and should be started as soon as possible the avoid the life threatening visceral complications.

Adolescent↗
PubMed1994

Cross-sectional study of the susceptibility of Candida isolates to antifungal drugs and in vitro-in vivo correlation in HIV-infected patients.

OBJECTIVES: To investigate (1) the frequency of clinical resistance to oral polyenes or azole treatment for oral candidiasis, (2) the frequency of resistant in vitro Candida strains, (3) the relationship between the susceptibilities of in vitro Candida species and in vivo status in HIV patients. DESIGN: Prospective cross-sectional study. SETTING: Tertiary care clinic at Bocage Hospital, Dijon, France. PATIENTS: HIV-infected patients with and without oral candidiasis. INTERVENTIONS: Clinical examination, oral swab for mycologic investigations. MAIN OUTCOME MEASURES: Clinical diagnosis of oral candidiasis, identification of the antifungal treatment given within the previous month, identification of Candida species, antimycogramm and determination of the minimal inhibitory concentration (MIC) for fluconazole, and measurement of T-helper cell count. RESULTS: Within a 2-month period, 154 HIV-infected patients were studied: 46 heterosexuals, 51 intravenous drug users (IVDU), 52 homosexuals and five blood transfusion recipients. The percentages of patients with oral candidiasis were: 41, 80, 44 and 20%, respectively (P < 0.05); the mean T-helper cell counts were 200, 135, 210 and 238 x 10(6)/l cells, respectively (P < 0.05). Twenty-two patients (14.3%) had received recent azole treatment and 29 (18.8%) recent oral polyene treatment. Among the 84 patients with and the 70 patients without oral candidiasis, 78 and 28 Candida strains were isolated, respectively. Although Candida albicans represented the majority of Candida species (88 strains, 83%), the non-albicans strains were isolated more frequently in patients who had received recent antifungal treatment. No strains were resistant to ketoconazole, miconazole or econazole; however, six (5.6%), 16 (15%) and 10 (9.5%) were intermediately susceptible to the three drugs, respectively. Twelve (13.6%) of the 88 C. albicans, five of the six C. (Torulopsis) glabrata, one of the five C. tropicalis and all three C. krusei strains were resistant to fluconazole. These resistant strains were separated as follows: 41.1% of C. albicans strains resistant to fluconazole were isolated from patients who had received recent azole therapy, 17.6% from patients who received recent oral polyene, and 3.7% from patients who had not received any recent antifungal treatment (P = 0.004). The mean MIC of these three categories of isolates were 3.6, 1.6 and 0.6 mg/l, respectively (P = 0.06). CONCLUSIONS: Oral candidiasis and fluconazole-resistant Candida isolates are more frequently found in IVDU. Treatments using azoles select non-albicans strains and are associated with decreased susceptibilities of C. albicans strains to fluconazole in particular. These findings show that prolonged azole treatment in severely immunocompromised patients should be avoided.

AIDS-Related Opportunistic Infections↗
PubMed1994

Changes in the dominant Epstein-Barr virus type during human immunodeficiency virus infection.

Two types of Epstein-Barr virus (EBV), EBV-1 and EBV-2, were identified on the basis of DNA sequence divergence in the genes for nuclear proteins EBNA 2, 3a, 3b and 3c. In the present study, we conducted an immunological and genomic analysis in a human immunodeficiency virus (HIV)-infected population to determine the prevalence of the two types, and whether the identified type was stable over years. The EBNA-2 serotyping and genotyping showed that HIV-infected patients were highly infected by EBV-2, and that the dominant strain was mostly retained. However, during a follow-up study, a change in the dominant viral strain was observed in two patients. A first HIV-positive patient (patient A), although having a stable level of anti-EBNA-2A and -2B antibodies, showed a change in the genotype and antigen produced in spontaneously established lymphoblastoid cell lines (LCL). The sequence analysis of LCLs confirmed the emergence of the EBV-2 type population. A strain from a second HIV-positive patient (patient B) was clearly identified as EBV-2: the genotype from a saliva sample and from sequential LCLs belonged to EBV-2, as well as the antigen produced from LCLs, and serum antibodies. After a 5-year continuous EBV-2 infection, a reactivation of the EBV-1 strain was observed. In both cases, sequence analysis of the EBNA-2 gene showed, only with EBV-1, the presence of EBV variants related to the B95-8 prototype. Two mutations (at nucleotides 49212 and 49304) were found in both patients A and B, whereas an additional mutation (at nucleotide 49237) was characteristic of the patient A. No mutation relative to the prototype B95-8 strain was observed in a subsequent analysis of this EBNA-2 region from LCLs obtained from two HIV-negative patients predominantly infected by EBV-1. Therefore, we speculate that these mutations may be EBV-1 mutations specifically occurring during HIV infection.

Antigens, Viral↗
PubMed1992

Clinical evaluation of a new lipid-based delivery system for intravenous administration of amphotericin B.

In a retrospective study a new lipid-based delivery system for administration of amphotericin B was evaluated in 26 treatment courses in 22 patients. Amphotericin B was given by infusion diluted in either the lipid solution (1 mg/kg/d; 13 courses) or dextrose (0.92 mg/kg/d; 13 courses). No differences were noted in the serum pharmacokinetics. Fever or rigors were observed in 6 of 13 courses in the conventional amphotericin B group versus none in the lipid amphotericin B group (p = 0.007). Four of 13 courses of treatment were discontinued due to adverse effects in the conventional amphotericin B group compared to none in the other group (p = 0.048). In the lipid amphotericin B group the decrease in creatinine clearance was significantly lower on the fourth day of treatment (p = 0.04) and significantly fewer patients had a decrease of more than 25% in creatinine clearance on the sixth day (4/12 vs 9/11 p = 0.02). These preliminary findings suggest that this lipid amphotericin B formulation is well tolerated with few nephrotoxic effects.

Adult↗
PubMed1992

Characterization of an R-binding site mediating the R-induced activation of the Epstein-Barr virus BMLF1 promoter.

In cells latently infected with Epstein-Barr virus, the switch from latency to productive infection is linked to the expression of two Epstein-Barr virus transcription factors called EB1 and R. R is an enhancer factor, and an R-responsive element (RRE) has been identified in the BMLF1 promoter. In this study, we have used bidirectional deletion mutagenesis to delineate the BMLF1 RRE (RRE-M) to a 44-bp sequence. We also show that R expressed from a recombinant vaccinia virus protects RRE-M against digestion by DNase I. Using mobility shift assays and dimethyl sulfate interferences, we have characterized the contact points between in vitro-translated R and the DNA. R binds in vitro to one site by simultaneously contacting two sequences within the site, which are separated by 8 bp: 5'-catGTCCCtctatcatGGCGCagac-3'. Site-directed mutagenesis of this sequence completely impaired the binding of R in vitro and rendered the BMLF1 promoter nonresponsive to R. The results suggest that the R-inducible BMLF1 enhancer is composed of a single R-binding site, called RRE-M.

Binding Sites↗
PubMed1992

Anti-Epstein-Barr virus-nuclear antigen-1, -2A and -2B antibodies in rheumatoid arthritis patients and their relatives.

We have examined serum antibodies to Epstein-Barr virus Nuclear Antigen (EBNA)-1, -2A and -2B, in addition to antibodies to viral capsid antigen and early antigen in 100 rheumatoid arthritis patients and 50 of their relatives. Using indirect immunofluorescence on transfected cells and Western-blot technique, we have found increased frequency and titres of antibodies to EBNA-2B in patients and, to a lesser degree, in their family members, whereas other anti-Epstein-Barr virus antibodies appeared to be similar to controls. Cross-inhibition experiments were carried out and show that antibodies to EBNA-2A are distinct from those to -2B, and vice versa.

Adult↗
PubMed1991

Transcriptional interference between the EBV transcription factors EB1 and R: both DNA-binding and activation domains of EB1 are required.

The switch from latency to a productive infection in EBV-infected B cells is linked to the expression of two viral sequence-specific DNA-binding transcription factors called EB1 and R. EB1 shares sequence homologies with the bZIP family of proteins in the basic region required for specific DNA interaction. Here, we provide evidence that EB1 and R can synergistically activate specific transcription, and that overexpressed, unbound EB1, represses the R-induced transcription ('squelching'). In order to identify the EB1 domains involved in transcriptional activation, transcriptional synergy and transcriptional repression, we performed extensive mutagenesis of the EB1 protein. Results show that five segments (region 1 to region 5), localized at the N-terminus of EB1 exhibit characteristics of activating domains, since they are required for full transcriptional activity, without obvious role in DNA-binding, or the nuclear localization. Two domains rich in basic amino-acids are required for the nuclear localization of EB1. One domain is within the basic region B, also necessary for specific and stable interaction between EB1 and its cognate DNA sequences. It is also shown that the 'activation' domain, and more surprisingly the DNA-binding domain of EB1, may interact with a factor(s), essential for R-induced activation, and probably required for synergy between EB1 and R.

Amino Acid Sequence↗
PubMed1990

A double-blind randomized placebo trial on very high doses of acyclovir in weakly symptomatic HIV-patients.

Herpesvirus infections are thought to be cofactors of the human immunodeficiency virus (HIV) disease, and high concentrations of acyclovir (ACV) are active on all herpesviruses. Because ACV was shown to delay the cytopathic effect of HIV in vitro, we evaluated the effect of intermittent high doses of ACV in mildly symptomatic HIV-patients in a randomized double-blind placebo-controlled trial with a 4-month treatment period. A total of 30 CDC II and III patients were enrolled; 24 (80%) completed the study. Placebo and ACV were given once a week in a 3-h infusion with 1 g oral probenecid. Each dose of ACV was 50 mg/kg. Pharmacokinetic data were obtained from patients of the preliminary open study. The obtained concentrations were effective against both herpesviruses and HIV: peak concentrations were 197 and 11 mumol/l in serum and CSF, respectively; the CSF:serum ratio of the areas under the curve was 82%. Two patients with placebo acquired hairy leukoplakia and detectable antigenemia vs. none in the ACV group (p = 0.23). T-helper cell count over the 4-month period decreased in the placebo group while it increased in the ACV-treated group (mean of change = -105 c/microliters vs. +68 c/microliters; p = 0.06). beta 2-microglobulin increased with placebo and did not with ACV (mean of change = +0.63 mg/l vs. -0.27 mg/l, p less than 0.025). Only one patient had, at one time, transient elevation of creatinemia related to ACV. We concluded that weekly high doses of ACV were able to delay the progression of some significant markers of HIV disease. Thus, preventive/prophylactic treatment of herpesvirus infections could be useful in mildly symptomatic HIV patients. Further larger trials using a more feasible treatment are warranted.

Acyclovir↗
PubMed1989

The Epstein-Barr virus early protein EB1 activates transcription from different responsive elements including AP-1 binding sites.

When expressed in Epstein-Barr virus (EBV) latently infected B cells, the EBV early protein EB1 trans-activates as many EBV early genes as does TPA. Several EB1 responsive elements (ZRE) have been identified in EBV early promoters and are located at relatively short distances from the TATA box. One of them (ZRE-M) overlaps with a consensus TPA responsive element (TRE) defined as an AP-1/c-jun/c-fos binding site and is located in an EBV promoter controlling the expression of the post-transcriptional activator EB2. Another (ZREZ) is located in the promoter controlling the expression of EB1 and does not respond to TPA. These two ZREs have no apparent sequence homology. Although EB1 activates transcription from the AP-1 enhancer sequence and from the ZREZ, the activation is severely impaired by distance, suggesting that EB1 is more likely to be a promoter factor than an enhancer factor. These properties also suggest that EB1 is not functionally related to c-jun and c-fos. However, since EB1 can activate transcription from AP-1 binding sites when properly positioned, the role of this factor in the oncogenic properties of EBV should be considered.

Base Sequence↗