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J Icart

Publications and source records attributed to J Icart.

At least 19 recordsLinked to original sources

Tissue specific distribution of Epstein-Barr virus (EBV) BZLF1 gene variants in nasopharyngeal carcinoma (NPC) bearing patients.

Using EBV BNLF1 gene polymorphism, we have recently shown that, in NPC bearing patients, lymphocytes and tumor cells of the same individual were infected by different viruses. It appeared as a rule that EBV infection was by multiple strains in these immunocompetent, HIV negative patients. Our data did not detect any evident association between tumor cells and a particular BNLF1 variant. In the present paper, we extend our analysis to the BZLF1 gene of the viruses present in different sites of the same patients. Only two main variants of the BZLF1 gene were identified. Despite this very weak polymorphism of this locus, our results entirely confirm the very frequent occurrence of multistrain infections in these patients, and the presence of different EBV strains in tumor cells and lymphocytes from the same individual. However, in contrast to our results concerning the BNLF1 gene, the BZLF1 variants appeared to be cell type specific, one being associated mainly with epithelial or tumor cells and the other with lymphocytes. The possible reasons for this distribution are discussed.

Animals↗

Nosocomial outbreak of influenza virus A (H3N2) infection in a solid organ transplant department.

BACKGROUND: There is a strong body of evidence in favor of influenza virus immunization in solid organ recipients. However, little attention has been devoted to other reservoirs, such as the patients' relatives and, at the time of hospital admission, to the healthcare workers. METHODS: Analysis of the epidemiology of an outbreak of nosocomial influenza A in a solid organ transplant unit. RESULTS: Four cases of influenza A virus infection were reported during a short 4-day outbreak in a 12 single-room transplant unit. None of the patients had been immunized against influenza. Three patients had not been visited by their relatives between admission and influenza infection. Three nurses, among the 27 healthcare workers, presented with clinical flu symptoms at times consistent with nosocomial transmission. CONCLUSIONS: Because the prevention of influenza infection by vaccination warrants a global strategy to target the different reservoirs, we suggest that the modern policy of vaccinating solid organ patients should be extended both to their relatives and to the healthcare workers of transplant units.

Adult↗

In nasopharyngeal carcinoma-bearing patients, tumors and lymphocytes are infected by different Epstein-Barr virus strains.

Despite the fact that most adult humans worldwide are latently infected by the Epstein-Barr virus (EBV), only a very small percentage of them will develop an EBV-associated malignancy. We do not know whether this situation reflects the existence of more sensitive individuals or of particularly tumorigenic EBV strains. We postulated that if highly tumorigenic EBV strains did exist, they would be preferentially found in consistently EBV-associated tumors, such as nasopharyngeal carcinoma (NPC), and differ significantly from the strains present in other, non-pathological sites of the same patients. To test this hypothesis, we compared the BNLF1 gene of the EBV strains present in tumors and in "reservoir lymphocytes" of 6 NPC-bearing patients from Tunisia. Our results show that all of these patients were infected by more than 1 (and up to 7) EBV strains. Moreover, lymphocytes and tumor cells from the same individual were systematically infected by different viral strains. The origin and biological significance of these multistrain infections are discussed.

Adult↗

JC virus genotypes in France: molecular epidemiology and potential significance for progressive multifocal leukoencephalopathy.

JC virus (JCV) induces progressive multifocal leukoencephalopathy (PML), especially in human immunodeficiency virus (HIV)-infected patients. Although JCV genotypes have primarily been associated with geographic patterns, a distinctive neuropathogenicity was recently attributed to genotype 2. A multicenter study was conducted to describe the distribution of JCV genotypes in France and to investigate correlations between genotypes and PML. Genotypes were determined by sequencing 494 bp in the VP1 capsid gene. Peripheral JCV was studied in 65 urine samples from 43 HIV-infected patients and from 22 control subjects. Genotypes 1, 4, 2, and 3 were detected in 52.3%, 30.8%, 12.3%, and 4.6% of the samples, respectively. In 56 brain or cerebrospinal fluid samples, PML-associated JCV of genotypes 1, 2, 4, and 3 was found in 66%, 19.7%, 8.9%, and 5.4%, respectively. Infection with JCV genotypes 1 or 2 was correlated with PML (odds ratio, 3.29). On the other hand, infection with JCV genotype 4 could represent a lower risk for PML.

AIDS-Related Opportunistic Infections↗

Genomic variations in echovirus 30 persistent isolates recovered from a chronically infected immunodeficient child and comparison with the reference strain.

Seven sequential isolates of echovirus type 30 (EV30) were recovered over 22 months from a child with severe combined immune deficiency syndrome. The nucleotide sequences of the 5' halves of the genomes (4,400 nucleotides) of the first (S1) and last (S7) isolates were determined and compared with that of the EV30 Bastianni reference strain, also determined in this study. In genome regions P1 and P2, 101 variations were identified between the two isolates. Synonymous differences far outnumbered nonsynonymous differences. Amino acid changes affected both capsid and nonstructural polypeptides (particularly 2B). The VP1 nucleotide sequences of the seven isolates were determined to analyze genome evolution during the chronic infection. In the phylogenetic tree, the seven isolates were directly related to the prototype strain in an individual monophyletic group, strongly suggesting that the chronic infection in the child arose from a single persistent EV30 isolate. Four lineages were observed in the persistent isolates. Isolates S2, S4, S5, and S6 were close relatives of one another, whereas isolates S1 and S3 formed individual lineages. Isolate S7, distantly related to all other isolates, formed the fourth lineage. These findings suggest the quasispecies nature of the genomes of the seven sequential EV30 isolates. Grouping of persistent isolates on the basis of replicative capacities was consistent with phylogenetic relationships. Overall, the results indicate that genetically related EV30 variants with different replicative capacities coexisted in a carrier state, probably in the gastrointestinal tract, during the infection of the child.

5' Untranslated Regions↗

High Epstein-Barr virus serum load and elevated titers of anti-ZEBRA antibodies in patients with EBV-harboring tumor cells of Hodgkin's disease.

Hodgkin's disease is commonly associated with EBV latent infection. The incidence of EBV reactivation (active infection or EBV infection with replicative cycle) was evaluated in a series of 30 patients with untreated Hodgkin's disease (except for one case with chronic lymphocytic leukemia) by quantitation of EBV DNA and titration of anti-ZEBRA antibodies in serum samples. DNA was detected in serum (>2.5 x 10(2) genomes/ml) in 15 of 30 patients and was more frequent in Hodgkin's disease with EBV-positive Reed-Sternberg cells (10/12) than in EBV-negative cases (5/18), (P< 0.01). Of interest was the demonstration that viremia correlated well with increased titers of anti-ZEBRA IgG and/or standard serological profiles of EBV reactivation (12/15), (P < 0.05). However the lack of EBV replicative cycle in Reed-Sternberg cells (negative for ZEBRA antigen and early antigen BHLF1) suggests that the viral replication occurs in a nonneoplastic cell compartment rather than in tumor cells. The measurement of EBV DNA loads and the titration of anti-ZEBRA antibodies shed new lights on the link between activation of EBV replication and Hodgkin's disease: these serological markers together with the determination of the EBV status of the tumor suggest that replication of the viral genome occurs with a decreased efficiency of the immune system, thus allowing progression of the tumor.

Adolescent↗

[Chickenpox in pregnancy].

Chickenpox is rare during pregnancy (1 to 7 per 10,000). The infection can be severe for the mother and indirectly may affect the fetus. Before 20 weeks of amenorrhea, the varicella-zoster virus may be responsible for a rare embryofetopathy (incidence rate: 0.4 to 2%). After the 20th week of amenorrhea, fetal infection is not symptomatic, but it may lead to neonatal or infantile herpes zoster infection. During the perinatal period, a primary maternal infection may be responsible for severe neonatal varicella if delivery occurs prior to maternal antibody production. Practical guidelines are proposed according to the date of infection during pregnancy and prenatal diagnosis using amniocentesis and/or cordocentesis is discussed.

Chickenpox↗

Prevalence of JC virus viraemia in HIV-infected patients with or without neurological disorders: a prospective study.

Progressive Multifocal Leukoencephalopathy (PML) is a severe demyelinating disease, which is rapidly fatal and is due to JC virus (JCV) infection, which especially occurs in HIV-infected patients. To investigate JCV pathophysiology and to evaluate the predictive value of JCV detection in blood, we looked for JCV DNA in leukocytes and plasma of 96 patients without any neurological symptoms and 109 patients with neurological diseases, among whom 19 were suffering from PML. JCV genome was detected in about 18% of all patients, i.e. 15.6% of patients with central nervous system disorders except PML, 13.5% of patients without neurological symptoms and significantly more often in PML patients (47.6%). Both leukocytes and plasma were tested; in plasma, JCV DNA was found in 36.1% of positive patients and in cells in 80.5%. Surprisingly in seven instances only the plasma contained JCV genome. One-year follow-up of these patients showed that the absence of JCV DNA in blood was associated with a very low probability of developing PML (negative predictive value=0.99).

Blotting, Southern↗

Efficacy and safety of lamivudine on replication of recurrent hepatitis B after cadaveric renal transplantation.

BACKGROUND: The aim of this pilot study was to evaluate the efficacy and the safety of lamivudine therapy in hepatitis B virus (HBV)-positive/DNA-positive renal transplant recipients. METHODS: Six HBV DNA-positive cadaveric renal transplant recipients ranging in age from 49+/-6 years were administered lamivudine, at 100 mg/day for a period of at least 6 months, on a compassionate-use basis. Lamivudine is the (-) enantiomer of 3'-thiacytidine, which is known to be a potent inhibitor of HBV replication. All of the patients but one were on cyclosporine-based immunosuppression. RESULTS: The mean serum creatinine was 134+/-44 micromol/L. The mean duration of HBV infection was 230+/-54 months (156-288). All of the patients but one had high serum alanine aminotransferase levels (122+/-52 IU/L; range, 45-243). Histological evaluation showed the presence of either chronic active hepatitis (n=4) or cirrhosis (n=2). All of the patients but one were hepatitis B e antigen negative/hepatitis B e antibody positive, but none were coinfected with either hepatitis C virus or hepatitis D virus. CONCLUSIONS: Lamivudine therapy was associated with (i) a normalization of alanine aminotransferase levels in four of five patients when these levels were increased at the beginning (n=5); (ii) a rapid disappearance of HBV DNA from the serum (detected by hybridization) in all of the patients; (iii) the negativity of HBV DNA by polymerase chain reaction in four patients; and (iv) no change in renal function and in proteinuria when present (one patient). Finally, no adverse effects were noted. When lamivudine therapy was stopped for four patients after 6 months, it was associated with a biochemical and virological relapse within the weeks that followed. Lamivudine therapy was therefore resumed for these patients.

Antiviral Agents↗

Prevalence of antibodies to hepatitis C virus and correlation with liver disease in renal transplant patients.

We studied the prevalence of hepatitis C virus (HCV) infection in 350 renal transplant (RT) patients with a functioning graft. The determination of HCV infection was based upon second-generation ELISA tests (ELISA-2, Abbott) confirmed by second-generation RIBA tests (RIBA-2, Chiron), including the proteins C22-3, C100-3, C33-C and 5-11. Three hundred and sixteen of these RT patients were on ciclosporin A (CsA) therapy with or without steroids (CS) and azathioprine (AZA); 34 received conventional immunosuppression. Eighty-seven RT patients were found to be HCV-positive (2.5%) when assessed by ELISA-2 tests; RIBA-2 was positive in 61 cases and 'indeterminate' in 26. Most of the HCV-positive patients had antibodies against C22-3 (94%), whereas antibodies against nonstructural antigens (C100-3, C33-C) were observed in 18 and 70% of cases, respectively. More than 88% of the HCV-positive patients were already HCV-positive before renal transplantation. Risk factors of developing HCV infection included: (i) the time on dialysis; (ii) the number of blood transufsions before transplantation, and (iii) the number of previous graft(s). There were significantly more HCV-positive patients among those on conventional immunosuppressive therapy (16 of 39) than among those on CsA (71 of 311; p < 0.02). Of those who where HCV-positive before transplantation, and for whom liver enzyme (LE) results were available (n = 68), 40 had either a normal or a transient increase in alanine aminotransferase (ALT) levels at that time, whereas 28 had a chronic increase in serum ALT +/- gamma-glutamyltranspeptidase levels. After transplantation, there was biochemical evidence of chronic liver disease in 33 patients (48.5%). Interestingly, 41 and 64% of those with respectively normal and increased LEs before transplantation presented with a biochemical chronic liver disease after RT. Surprisingly, 36% of those with a pretransplantation increase in ALT had normalized aminotransferase after transplantation. The daily doses of AZA, CS (i.e. prednisolone) were not statistically different between HCV-positive RT patients on conventional therapy (group A) and those on CsA (group B). Moreover, within each group, the daily doses of AZA, CS or CsA were not statistically different between those with a chronic increase in LEs and those with normal LEs. The percentage of HCV-positive RT patients with chronic abnormal LEs was not different between groups A and B. Surprisingly, the patients who were treated at least once for acute rejection with methylprednisolone pulses had a significantly lower incidence of chronic increases in LEs. Nine patients seroconverted for HCV after transplantation: 6 experienced a chronic increase in LEs. Finally, 7 of 87 patients were coinfected by HBV, all of them had a chronic increase in LEs. These results emphasize the fact that ALT alone cannot be used as a surrogate marker for chronic HCV infection in transplantation patients, thus a liver biopsy is required before and a few years after RT to assess liver damage in this population.

Adult↗

CMV prophylaxis in high-risk renal transplant patients (D+/R-) by acyclovir with or without hyperimmune (CMV) immunoglobulins: a prospective study.

In this prospective randomized study including 28 patients, we show that, in cytomegalovirus (CMV)-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+), high doses of acyclovir (ACV, i.e. 3,200 mg/day) during the first 3 months after transplantation were as efficient as hyperimmune CMV immunoglobulins (CMV Igs) plus high doses of ACV regarding the prophylaxis of CMV primoinfection. Fifty-four percent of the patients in the ACV arm and 50% in the other arm presented at least one episode of viremia (n.s.). The incidence of CMV disease was 31% in the ACV group and 20% in the ACV + CMV Ig group (n.s.). By comparison with historical controls (no prophylaxis), we found that ACV with or without CMV Ig significantly delayed and significantly decreased the rate of CMV disease, although the severity score was not statistically different. Moreover, high doses of ACV were far less expensive than their combination with hyperimmune CMV Igs. Thus, until oral ganciclovir is available for the prophylaxis of primary CMV infection in renal transplant patients, we recommend the use of high doses of ACV for the first 3 months after transplantation in high-risk renal transplant patients, i.e. D+/R-.

Acyclovir↗

[Is laryngeal papillomatosis always juvenile?].

After recording an increased frequency of adult-onset recurrent respiratory papillomatosis, the authors propose a multicentric investigation. The aim of the investigation is to determinate the frequency of the new cases and their clinical form. The preliminary results confirm the increased frequency of the adult-onset form and show the possibility of a clinical form change.

Adolescent↗

Intra-uterine fetal death following maternal varicella infection.

The association of varicella and pregnancy is very rare since 90% of women of reproductive age are immune. In the literature, a fetal varicella syndrome has been described characterized by multiple congenital malformations. We report here a case of intrauterine fetal death following maternal varicella at 17 weeks amenorrhea, with virological proof of fetal contamination. Because of the rarity of this association and by the same token of the fetal contamination during maternal varicella, the management during pregnancy rests essentially on a valid ultrasonic surveillance.

Adult↗

Inflammatory pseudotumor of the liver. Evidence for follicular dendritic reticulum cell proliferation associated with clonal Epstein-Barr virus.

We describe an "inflammatory pseudotumor" of the liver that, which on detailed investigation, proved that the spindle-cell component of this lesion is derived from follicular dendritic reticulum cells (FDRC). This contention is supported by morphologic observations and by immunophenotype. The FDRC population contain Epstein-Barr virus (EBV). It is known that FDRC express the EBV receptor CD21. In this particular case, the FDRC contained clonal EBV genomes, EBV RNA (EBER) transcripts, and expressed EBV latent membrane protein (LMP1). DNA sequencing of PCR products showed three point mutations compared with the standard LMP1 sequence of the EBV strain B95-8. The findings in this case corroborate those of other investigators concerning the possible role of EBV in the development of some inflammatory pseudotumors, including the recent production of functionally active EBV-transformed FDRC-like cell lines. This association could prove instructive in delineating the histogenesis of these tumors and further assist in making prognostic and therapeutic decisions.

Aged↗

Measurement by the polymerase chain reaction of the Epstein-Barr virus load in infectious mononucleosis and AIDS-related non-Hodgkin's lymphomas.

A polymerase chain reaction (PCR) assay for the detection of Epstein-Barr virus (EBV) sequences in various clinical samples, especially peripheral blood leukocytes (PBL) and serum, was carried out and the results obtained were compared with specific EBV serology. One hundred seventy patients were enrolled in the study: 89 healthy blood donors, 22 asymptomatic patients, 36 individuals with primary EBV infection (including 19 patients with infectious mononucleosis [IM]), 22 HIV-infected subjects (including 4 with hairy oral leukoplakia, 3 with central nervous disorders, and 15 with non-Hodgkin's lymphoma). All the serum samples from the healthy blood donors were negative. In patients with IM and in AIDS-non Hodgkin's lymphoma (ARNHL), PCR was strongly positive in leukocytes (> 2,000 genome equivalents/10(4) cells), which was correlated with detectable amounts of EBV DNA in serum. The overall positivity rate of PCR in serum was 58.8%, 68%, and 73% of cases for non-IM primary EBV infections, IM, and ARNHL, respectively. In two cases of EBV primary infection, the viral DNA was detected in serum, respectively 1 month and 2 months before IgM positivity and IgG rise. In one case of ARNHL followed up for several months, PCR (viral load of 2,000 genome equivalents/10(4) cells) became positive concurrently with appearance of lymphoma. In immunocompromised individuals, PCR EBV, if carried out in larger prospective studies, could be considered as a tumor marker, useful for predicting EBV-driven lymphoma and follow-up therapy.

Acquired Immunodeficiency Syndrome↗

[Guillain-Barré syndrome associated with cytomegalovirus infection after kidney transplantation].

The Guillain-Barré syndrome associated with cytomegalovirus infection is a recognized entity of unknown pathogenesis. We observed two characteristic cases with acute polyradiculoneuropathy which occurred after renal transplantation. Both patients fulfilled the diagnostic criteria for Guillain-Barré syndrome: tetraparesis with diffuse areflexia and moderate sensorial signs, high protein level in cerebrospinal fluid without cellular reaction, slow or blocked nerve conduction and partial cure after several months delay. In two-thirds of such cases, the syndrome follows an episode of infection. Cytomegalovirus has been recognized as a possible association. The demyelinating polyradiculoneuropathy induced by cytomegalovirus has been reported essentially in immunodepressed patients infected with the human immunodeficiency virus in whom a pathogenic role for cytomegalovirus in peripheral nerves has been suggested. In our two cases, the cytomegalovirus infection occurred before onset of the acute polyradiculoneuropathy. In both cases, specific IgM antibodies and clear IgG positivization occurred before the first signs of neurological impairment even though neither the virus nor specific antibodies could be concomitantly detected in the cerebrospinal fluid. Despite the frequency of cytomegalovirus infections in transplant recipients, to our knowledge, only 9 cases of Guillain-Barré syndrome after transplantation have been reported and the exact mechanism remains to be ascertained. These two cases suggest that the onset of the Guillain-Barré syndrome after renal transplantation was closely related to cytomegalovirus infection. Adequate measures should be taken to quickly diagnose such cases in order to instore rapid treatment for the polyradiculoneuropathy. In addition, this particular situation of post-transplantation onset might help better understand the exact role of cytomegalovirus infection in the Guillain-Barré syndrome.

Cytomegalovirus Infections↗

Epstein-Barr virus (EBV) replicative gene expression in tumour cells of AIDS-related non-Hodgkin's lymphoma in relation to CD4 cell number and antibody titres to EBV.

OBJECTIVE: To determine whether activation of Epstein-Barr virus (EBV) replication in tumour cells of AIDS-related non-Hodgkin's lymphoma (ARNHL) is correlated with CD4+ cell counts and influences antibody response to EBV [anti-Z Epstein-Barr replicative activator (ZEBRA), anti-early antigen (EA), anti-viral capsid antigen (VCA)]. DESIGN: Retrospective study based on immunohistochemistry and in situ hybridization to detect EBV replicative gene products in tissue samples from patients affected by ARNHL and correlation with CD4+ cell counts and results of EBV serology (including anti-ZEBRA activity) in sera from the same patients. METHODS: Seventeen out of 22 cases of ARNHL were selected for the presence of EBV [Epstein-Barr early region (EBER) RNA-positive]. Immunohistochemistry was performed with anti-ZEBRA, anti-EA-restricted, anti-VCA antibodies and in situ hybridization with BHLF1/NotI oligoprobes on tumour samples. Results were statistically correlated with those of CD4+ cell counts (17 out of 17) and with anti-EBV antibody titres (13 out of 17) assessed using standard immunofluorescence method and enzyme-linked immunosorbent assay procedure using recombinant ZEBRA protein and synthetic peptides as antigens. RESULTS: BZLF1 (ZEBRA) or early gene products (EA-R and EA-D/BHLF1/NotI) were detected in a small proportion (< 0.01-5%) of tumour cells in eight of these 17 cases by immunohistochemistry and in situ hybridization. Demonstration of replicative gene expression did not correlate with either low CD4+ cell counts (P > 0.05) or anti-EBV antibody titres (P > 0.05). Anti-ZEBRA activity was not significantly increased in patients affected with ARNHL, the cells of which expressed replicative gene products (P > 0.05). CONCLUSION: The degree of immunodeficiency does not clearly enhance replicative gene expression in tumour cells of ARNHL. EBV serology, including anti-ZEBRA activity, is not a reliable tool for predicting the occurrence of such proliferations.

Acquired Immunodeficiency Syndrome↗