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P Lebon

Publications and source records attributed to P Lebon.

At least 37 records · Page 2Linked to original sources
PubMed2002

Plasma exchange and interferon-alpha pharmacokinetics in patients with hepatitis C virus-associated systemic vasculitis.

UNLABELLED: Different types of vasculitis have been reported in association with hepatitis C virus (HCV) infection, i.e. type II mixed cryoglobulinemia and polyarteritis nodosa (PAN). Therapeutic approach of such severely symptomatic patients include interferon-alpha (IFN) plus plasma exchange (PE). There are no data on IFN pharmacokinetic changes related to PE. PATIENTS AND METHODS: We studied 7 HCV-infected patients (mean age: 57 years) presenting with symptomatic type II mixed cryoglobulinemia (n = 5) or biopsy-proven PAN (n = 2). All patients underwent subcutaneous IFN therapy with concomitant PE. Serum IFN concentration was measured in serial samples on days with and without PE. RESULTS: Without PE, IFN C(max )(range: 100-750 IU/ml) was obtained 3-6 h after subcutaneous injection, followed by a 3- to 9-hour plateau. IFN concentration declined subsequently reaching a residual concentration 24 h after injection, ranging from 20 to 40 IU/ml. PE performed 6 h after IFN administration resulted in increased IFN clearance in that the concentration-time IFN-alpha area under the curve decreased from 3,005 IU x h/ml (1,563-4,614) on days without PE to 2,142 IU x h/ml (973-4,123) on day with PE. CONCLUSIONS: In patients with HCV-associated vasculitis, PE increase IFN clearance. Combined IFN-alpha and PE therapy schedule have to be further studied to optimize its biological activity.

Aged↗
PubMed2001

Reduced blood CD123+ (lymphoid) and CD11c+ (myeloid) dendritic cell numbers in primary HIV-1 infection.

Successful immunologic control of HIV infection is achieved only in rare individuals. Dendritic cells (DCs) are required for specific antigen presentation to naive T lymphocytes and for antiviral, type I interferon secretion. Two major blood DC populations are found: CD11c+ (myeloid) DCs, which secrete IL-12, and CD123+ (IL-3-receptor+) DCs (lymphoid), which secrete type I interferons in response to viral stimuli. The authors have previously found a decreased proportion of blood CD11c+ DCs in chronic HIV+ patients. In this study, 26 to 57 days after infection and before treatment, CD123+ and CD11c+ DC numbers were dramatically reduced in 13 HIV+ patients compared with 13 controls (P =.0002 and P =.001, respectively). After 6 to 12 months of highly active antiretroviral therapy, DC subpopulation average numbers remained low, but CD123+ DC numbers increased again in 5 of 13 patients. A strong correlation was found between this increase and CD4 T-cell count increase (P =.0009) and plasma viral load decrease (P =.009). Reduced DC numbers may participate in the functional impairment of HIV-specific CD4+ T cells and be responsible for the low type I interferon responsiveness already known in HIV infection. The restoration of DC numbers may be predictive of immune restoration and may be a goal for immunotherapy to enhance viral control in a larger proportion of patients.

Adult↗
PubMed2001

Congenital HCMV infection: a collaborative and comparative study of virus detection in amniotic fluid by culture and by PCR.

Cytomegalovirus (HCMV) infection is the leading cause of congenital virus infection in developed countries, affecting an estimated 1% of births. This antenatal infection can cause serious sequelae. Strategies for prevention and treatment must, therefore, be agreed upon, entailing a preliminary performance assessment of antenatal virus diagnosis techniques. Between 1992 and 1999, HCMV serology status was established for 19456 pregnant women in four French hospitals. Seronegative patients (55.4%) were given serology screening, and antenatal diagnosis was given to 152 women who had shown seroconversion during their pregnancies (1.4%). The detection of HCMV transmission from mother to fetus was finally established in 95 cases, using polymerase chain reaction (PCR) and viral culture methods for detecting HCMV in the amniotic fluid. These results were compared with viral culture of children's urine after birth, enabling us to distinguish between children really infected in utero (30%) and non-infected children (70%). The results of the virus culture and those of PCR were identical in 94 of the 95 cases, with one discrepancy (culture-/PCR+). The two diagnosis techniques had identical sensitivity (72%), with culture proving slightly more specific than PCR (98.4% as opposed to 96.9%). Positive prediction values for culture and for PCR were, respectively, 95.6 and 91.3%. Antenatal virus diagnosis on amniotic fluid was negative with both techniques in 8 out of 29 cases of children born with HCMV infection (VPN=89%). Over half of these wrongly negative results can be explained by amniocentesis carried out too early in the pregnancy or too early with respect to the mother's primary infection.

Amniotic Fluid↗
PubMed2000

Antibody-dependent induction of type I interferons by poliovirus in human mononuclear blood cells requires the type II fcgamma receptor (CD32).

The induction of type I interferons (IFNs) in peripheral blood mononuclear cells (PBMCs) can be triggered by viral infection or exposure to viral glycoproteins. Here we show that the IFN-alpha-inducing capacity of attenuated poliovirus vaccine strains is dramatically enhanced in the presence of human polyvalent immunoglobulin G (IgG). The transcription of both IFN-alpha and IFN-beta genes was detected by RT-PCR in stimulated cells. This antibody-dependent activation of type I IFNs genes was also observed with Formalin-inactivated or UV-inactivated poliovirus, but not with empty poliovirus capsids. The ability of poliovirus-antibody complexes to induce IFN-alpha was specifically inhibited when PBMCs were preincubated with an excess of the Fc fragment of IgG. Monoclonal antibodies directed to FcgammaRII (CD32) were also inhibitory, whereas antibodies to the two other classes of Fcgamma receptors, CD16 and CD64, were not. Also, aggregation of FcgammaRII by anti-CD32 antibodies alone failed to induce IFN-alpha production. Our results suggest that induction of type I interferons by poliovirus-antibody complexes depends on CD32-mediated phagocytosis of RNA-containing viral particles. As suggested by the results of an ELISPOT analysis, only a fraction of the IFN-alpha-producing cells are able to synthesize IFN-alpha in response to poliovirus-IgG complexes.

Antibodies, Viral↗
PubMed2000

[Procalcitonin in pediatric emergencies: comparison with C-reactive protein, interleukin-6 and interferon alpha in the differentiation between bacterial and viral infections].

OBJECTIVE: Procalcitonin concentration increases in bacterial infections but remains low in viral infections and inflammatory diseases. The change is rapid and the molecule is stable making it a potentially useful marker for distinguishing between bacterial and viral infections. PATIENTS AND METHODS: Procalcitonin (PCT) was determined with an immunoluminometric assay on plasma collected at admission in 436 infants and children hospitalized for bacterial or viral infection. It was compared with C reactive protein, interleukin-6 and interferon-alpha measured on the same sample. RESULTS: PCT was 41.3 +/- 77.4 micrograms/l in children with septicemia or bacterial meningitis (n = 53), 0.39 +/- 0.57 microgram/l in children with viral infection (n = 274) and 3.9 +/- 5.9 micrograms/l in children with a localized bacterial infection who had a negative blood culture (n = 109). PCT was > 1 microgram/l in 126 children with a localized or systemic bacterial infection (sensitivity 78%). PCT was < 1 microgram/l in 258 children with a viral infection (specificity 94%). For differenciation between viral and bacterial infections, CRP value > or = 20 mg/l, IL-6 > 100 pg/ml and interferon-alpha > 0 Ul/ml have 85, 48 and 76% sensitivity and 73, 85 and 92% specificity respectively. CONCLUSIONS: In this study, a PCT value of 1 microgram/l or greater had better specificity, sensitivity and predictive value than CRP, IL-6 and interferon-alpha in children for distinguishing between viral and bacterial infections. PCT may be useful in pediatric emergency room for making decision about antibiotic treatments.

Adolescent↗
PubMed2000

Neurological complications of varicella-zoster virus infection in adults with human immunodeficiency virus infection.

This multicentre retrospective study describes the clinical features and prognostic significance of Varicella-zoster virus (VZV)-associated neurological complications. The study was performed in patients with human immunodeficiency virus (HIV) infection, hospitalized for VZV neurological complications, confirmed in every case by positive VZV polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). Between 1990 and 1995, 34 HIV-infected patients were included in the study. At diagnosis, 59% had AIDS, with a median CD4 count of 11 x 10(9)/l. A past history of zoster was noted in 35% of cases. A concomitant herpes zoster rash and/or acute retinal necrosis were noted in 71% and 12% of patients, respectively. The predominant neurological manifestations were encephalitis (13), myelitis (8), radiculitis (7) and meningitis (6). The mean CSF white blood cell count was 126/mm3 and the mean CSF protein concentration was 2.3 g/l. Interferon-alpha level was increased in 36% of patients. VZV was isolated from CSF cultures in 2/6 cases. Magnetic resonance imaging was abnormal, demonstrating encephalitis lesions. After intravenous antiviral therapy, complete recovery was obtained in 18 cases (53%), serious sequelae were observed in 10 cases (29%) and 6 patients died (18%). Severe symptoms and a low CD4 cell count appeared to be associated with death or sequelae. In conclusion, VZV should be considered as a possible cause of encephalitis, myelitis, radiculitis or meningitis in HIV-infected patients, especially in patients with a history of or concomitant herpes zoster or acute retinal necrosis. VZV-PCR in the CSF may allow rapid diagnosis and early specific antiviral treatment.

Adult↗
PubMed2000

No evidence of measles virus in stapes samples from patients with otosclerosis.

Otosclerosis is a localized bone dystrophy of unknown etiology mainly involving the stapes. The hypothesis of a persistent infection by the measles virus was based on the inconstant detection of the virus by various methods, including reverse transcription-PCR (RT-PCR) of patients' stapes samples. The aim of this work was to investigate the presence of the measles virus in stapedial otosclerosis foci by different sensitive methods. Pathologic stapes samples were obtained from 35 patients suffering from otosclerosis. Measles virus detection was performed by (i) cocultures of Vero cells and primary cell cultures of bone samples (n = 7), (ii) immunofluorescence study of these cocultures (n = 3), and (iii) RT-PCR on RNA directly obtained from fresh frozen samples (n = 28) and on RNA extracted from the primary cell cultures (n = 2). Viral genomic regions coding for N (nucleoprotein) and M (matrix) proteins were separately amplified. PCR sensitivity was optimized on the measles virus Edmonston strain. Glyceraldehyde-3-phosphate dehydrogenase mRNA was used as a marker of total RNA recovery. PCR products were tested by Southern blot hybridization technique to improve sensitivity and specificity. PCRs amplifying the M and the N protein genes were able to detect the control measles virus RNA at titers as low as 0.1 and 0.01 50% tissue culture infective dose, respectively. With these highly sensitive methods, we could not evidence the presence of the measles virus in any of our bone samples or primary bone cell cultures. Our results do not confirm the hypothesis of persistent measles virus infection in otosclerosis.

Adult↗
PubMed1999

[Severe forms of rubella encephalitis: arguments for a better vaccination policy].

BACKGROUND: Two cases of rubella encephalitis in young adults are reported. CASES REPORTS: 2 patients, 19 and 16-year-old, presented with severe encephalitis. One required mechanical ventilation. Neither were vaccinated against rubella. MRI scan of the brain was normal. The diagnosis was confirmed by serology. Good recovery was noted in both patients. DISCUSSION: Both cases of rubella encephalitis occurring in young adults illustrate the severity of this rare disease. As already shown in Finland, improvement with the French vaccination policy should lead to the prevention of rubella encephalitis.

Adolescent↗
PubMed1999

[Coincidental outbreaks of rotavirus and respiratory syncytial virus in Paris: a survey from 1993 to 1998].

PATIENTS AND METHODS: In a pediatric hospital of Paris, from 1993 to 1998, respiratory secretions were positive for respiratory syncytial virus (RSV) in 26.3% of 4,738 children (0-5 years) examined or hospitalized for lower respiratory tract infections. Rotavirus detection was positive in stools of 23.7% of the 8,537 children of the same age with acute diarrhea. RESULTS: The RSV epidemic peak occurred annually in Paris in December and the rotavirus outbreak peaks were observed in December/January. The winter seasonal peaks remained constant for both pathogens and the temporal appearance of these peaks was constant from 1993 to 1998. Fifty to sixty-one percent of rotavirus and 77 to 92% of RSV infections were observed in November, December or January. These simultaneous outbreaks provoked important problems in hospital organization and prevention of nosocomial infections. CONCLUSION: The coincidence of RSV and rotavirus peaks is not found in all countries. The epidemic patterns have to be checked in other parts of France and Europe because this could be important when active immunization programs will be available for these two pathogens.

Child, Preschool↗
PubMed1999

Aicardi-Goutières syndrome: monogenic recessive disease, genetically heterogeneous disease, or multifactorial disease?

Aicardi-Goutières syndrome (AGS) is a severe progressive familial encephalopathy, which is usually diagnosed shortly after birth. Using the principle of homozygosity mapping, genome-wide screening of five consanguineous families was performed to search for a homozygous region shared by all affected individuals. A total of 364 markers with an average spacing of 9.9 cM were genotyped, but no homozygous region common to all affected individuals could be found. Regions of homozygosity in affected sibs could only be identified within each family individually. This may reflect genetic heterogeneity, possibly related to clinical heterogeneity, since several syndromes are clinically difficult to distinguish from AGS. Involvement of a small number of genes and/or of an external factor, such as infection, may also explain the absence of a homozygous region common to all affected individuals.

Abnormalities, Multiple↗
PubMed1999

Progressive multifocal leucoencephalopathy with peripheral demyelinating neuropathy after autologous bone marrow transplantation for acute myeloblastic leukemia (FAB5).

Progressive multifocal leucoencephalopathy is an opportunistic JC virus-related pathology occurring in immunocompromised patients. We report a case of severe cellular immunodeficiency in a patient who underwent autologous bone marrow transplantation for acute myeloblastic leukemia, and who subsequently developed progressive multifocal leucoencephalopathy, an unusual pathology in this context. Progressive multifocal leucoencephalopathy was preceded by a peripheral demyelinating neuropathy. We discuss the possible link between these two neuropathies, the possible aggravation or activation from CMV infection, as well as the possible contribution of bone marrow purging in the resultant cellular immunodeficiency.

Adult↗
PubMed1999

Inhibition of interferon-inducible MxA protein expression by hepatitis B virus capsid protein.

Chronic hepatitis B treatment has been significantly improved by interferon (IFN) treatment. However, some studies have suggested that hepatitis B virus (HBV) might have a direct effect on the resistance to IFN. Defective particles, generated by spliced HBV RNA and associated with chronic hepatitis B, have been previously characterized; expression of these particles leads to cytoplasmic accumulation of the capsid protein. The aim of this study was to investigate the role of these defective genomes in IFN resistance. The global antiviral activity of IFN was studied by virus yield reduction assays, the expression of three IFN-induced antiviral proteins was analysed by Western blotting and confocal microscopy, and the regulation of MxA gene expression was studied by Northern blotting and the luciferase assay, in Huh7 cells transfected with a complete or the defective HBV genome. Results showed that the expression of the defective genome reduces the antiviral activity of IFN and that this modulation involves a selective inhibition of MxA protein induction by the HBV capsid protein. Our results also show the trans-suppressive effect of the HBV capsid on the MxA promoter, which might participate in this phenomenon. In conclusion, this study shows a direct interplay between the IFN-sensitive pathway and the capsid protein and might implicate this defective HBV genome in virus persistence.

Blotting, Northern↗
PubMed1999

Measuring HIV-1 RNA and interferon-alpha in the cerebrospinal fluid of AIDS patients: insights into the pathogenesis of AIDS Dementia Complex.

The aim of this work was to study the role of HIV replication and the role of endogenous secretion of interferon-alpha in the pathogenesis of AIDS Dementia Complex (ADC). To accurately establish the diagnosis of ADC, 39 consecutive HIV-positive patients who presented with immune and intellectual deficiency underwent an extensive neurological evaluation. This included magnetic resonance imaging, neuropsychological testing and a lumbar puncture. The levels of HIV-1 RNA were measured in the cerebrospinal fluid (CSF) and blood by HIV Monitor (Roche Diagnostics) and those of interferon-alpha by an in-house biological assay. The diagnosis of ADC was established in 22 cases, which included nine out of the ten patients who had a high CSF viral load (above 4 log HIV-1 RNA copy per ml). Patients receiving highly active antiretroviral therapy had low viral loads in blood and CSF. In all 22 ADC patients, viral load in the CSF correlated with the staging of ADC (r=0.46, P=0.03), the CSF level of interferon-alpha (r=0.42, P=0.05) and with the bicaudate ratio (r=0.43, P=0.06), a measure of cerebral atrophy in the region of the caudate nucleus. No correlation was observed between CSF and plasma HIV-1 RNA. These results show that HIV may play a role in the neurological impairment of ADC patients possibly in part through the deleterious effect of interferon-alpha on the central nervous system and that highly active combination therapy should reduce or prevent these complications.

AIDS Dementia Complex↗
PubMed1999

FCgammaRII (CD32)-dependent induction of interferon-alpha by serum from patients with lupus erythematosus.

Interferon-alpha (IFN-alpha) is detected in the serum of 70-80% of patients with systemic lupus erythematosus (SLE). Furthermore, soluble factors in SLE serum can induce peripheral blood mononuclear cells (PBMC) to produce IFN-alpha. The purpose of this work was to investigate the mechanism of this IFN-alpha induction. In eleven of fifteen SLE serum samples, an IFN-alpha inducing activity was detected, whereas serum from healthy controls, patients with other autoimmune disease and patients with viral infections were ineffective under the same conditions. After gel filtration of the serum, the inducing activity was found in the same fraction as IgG. The IFN-alpha inducing activity was inhibited by native monoclonal antibodies to the receptors for the Fc portion of IgG: FcgammaRIIA/C and FcgammaRIIB subclasses (CD32) and by their F(ab)'2 fragments. Purified Fc fragments of human IgG were also effective in abolishing the IFN-alpha-inducing activity. Since no anti-CD32 autoantibodies were found in SLE serum, this IFN-alpha-inducing activity may be due to immune complex antibodies. Such results may allow better understand the origin of endogenous IFN-alpha, which has a deleterious effect on the course of this autoimmune disease. The inhibition of this function by the CD32 antibody could lead to new therapeutic approach in SLE.

Antibodies, Monoclonal↗
PubMed1999

[Pulmonary infection from Rhodococcus equi after renal transplantation. Review of the literature].

Rhodococcus Equi, a strictly aerobic Gram positive coco-bacillus, is a pathogen for horses and foals. It may induce opportunistic infections and is described in AIDS infected patients. We report the case of a 47-year old man, breeder of horses, with kidney transplant who has presented, 8 years after his graft, an impairment of health, a fever and evidence of pulmonary disease. The pulmonary biopsy under scanner guidance and microbiology study, has displayed the diagnosis of Rhodococcus equi infection. The evolution has been favorable with double antibiotherapy (follow-up 27 months). Ten comparable observations have been published after organ transplantation: (kidney: 8; heart: 1; liver: 1). Pulmonary locations are widely predominant. The animal contact is found only in 30% of cases. The presentation of the sickness has been compared to pulmonary tuberculosis or to nocardiosis, pathologies often observed in this context of immunosuppression. The antibiotic treatment is difficult and should required two bactericidal antibiotics. A surgical lobectomy can be envisaged in case of relapse. The mortality is 30%.

Actinomycetales Infections↗
PubMed1998

Induction of interferon-alpha by glycoprotein D of herpes simplex virus: a possible role of chemokine receptors.

The induction of type I interferons by most RNA viruses is initiated by virus-derived double-stranded (ds)RNA. However, retro- and DNA-viruses, which do not synthesize dsRNA, must rely on different mechanisms of induction. For human immunodeficiency virus type 1 (HIV-1), recombinant glycoproteins 120 or 160 suffice to induce interferon (IFN)-alpha in blood-derived lymphocytes [H. Ankel, M. R. Capobianchi, C. Castilletti, and F. Dianzani (1994). Virology 205, 34-43]. Here we show that for herpes simplex virus type 1 (HSV-1) recombinant glycoprotein, gD is the major inducer, whereas gB, gC, gE, gG, gI, and the complex of gH and gL are poor inducers. The recombinant extramembrane fragment of gD was sufficient to induce IFN-alpha levels comparable to that of intact virus. Like with HIV-1, induction was inhibited by a monoclonal antibody that recognizes cerebrosides and sulfatides. Furthermore, monoclonal antibodies specific for the chemokine receptors CCR3 and CXCR4 also blocked induction. We conclude that HSV-1 induces IFN-alpha by interaction of its glycoprotein gD with appropriate receptors on IFN-producing cells. Based on the known receptor roles of galactosyl cerebrosides and chemokine receptors in HIV infection, such structures on IFN-producing cells could also participate in the induction of IFN-alpha by HSV-1.

Animals↗
PubMed1998

Characterization of the human analogue of a Scrapie-responsive gene.

We have recently described a novel mRNA denominated ScRG-1, the level of which is increased in the brains of Scrapie-infected mice (Dandoy-Dron, F., Guillo, F., Benboudjema, L., Deslys, J.-P., Lasmézas, C., Dormont, D., Tovey, M. G., and Dron, M. (1998) J. Biol. Chem. 273, 7691-7697). The increase in ScRG-1 mRNA in the brain follows the accumulation of PrPSc, the proteinase K-resistant form of the prion protein (PrP), and precedes the widespread neuronal death that occurs in late stage disease. In the present study, we have isolated a cDNA encoding the human counterpart of ScRG-1. Comparison of the human and mouse transcripts firmly established that both sequences encode a highly conserved protein of 98 amino acids that contains a signal peptide, suggesting that the protein may be secreted. Examination of the distribution of human ScRG-1 mRNA in adult and fetal tissues revealed that the gene was expressed primarily in the central nervous system as a 0.7-kilobase message and was under strict developmental control.

Adult↗