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Biomedical subjects

F Simon

Publications and source records attributed to F Simon.

At least 145 records · Page 8Linked to original sources

HIV type 1 diversity in northern Paris, France.

During a 6-month period, we studied the diversity of HIV-1 subtypes in 392 adult patients seen in Bichat-Claude Bernard Hospital, northern Paris, France. All the samples were serotyped and a subset was genotyped by means of HMA. Serotyping was performed with a new peptide subtype-specific EIA (SSEIA), based on in vitro competition for antibody binding between the representative V3 peptides of the different clades (A to E). HMA with plasmids from clades A to H gave unambiguous results on 105 of the 116 samples tested. The agreement between SSEIA and HMA was 36/41 for subtype B, 2/2 for subtype D, and 4/5 for subtype E. We found a discrepancy in the results between clade A and C: the patients with sera reacting to peptide C were confirmed by HMA as being infected by clade A strains. Three patients reactive with peptide A were infected by a subtype F. These results indicate that peptide cross-reactivity, even in the SSEIA format, hinders serotyping. In 11 samples, all from African patients, the subtype remained indeterminate because PCR or HMA failed. Caucasian patients (n = 223) were mainly infected by subtype B. HMA and/or SSEIA revealed non-subtype B infection in 14 Caucasians, who were infected by the sexual route overseas or in France. Patients originating from other countries (mainly in Africa) exhibited a broad strain diversity, with most of the different subtypes so far described being represented. This study confirms the frequency of subtype B strains in Caucasians living in France, but emphasizes the emergence of the different HIV-1 subtypes in Paris, together with the extent of strain trafficking. Discordances between serotype and genotype assays confirm that both tests require additional development.

Adult↗

Neonatal characteristics in rapidly progressive perinatally acquired HIV-1 disease. The French Pediatric HIV Infection Study Group.

OBJECTIVE: To identify clinical and laboratory parameters at birth that are associated with the rapidly progressive form of human immunodeficiency virus type 1 (HIV-1) disease in children born to infected mothers. DESIGN: Multicenter, prospective study of infants born to HIV-seropositive mothers. SETTING: A total of 62 obstetric and pediatric centers in France. PARTICIPANTS: Of 1386 children born to HIV-1-seropositive mothers at least 18 months before the cutoff date, 267 were infected. Infection was defined as serological positivity at 18 months or death from HIV disease before the age. MAIN OUTCOME MEASURE: Category C events (including opportunistic infections, recurrent severe bacterial infections, cancers, specific encephalopathy, and wasting syndrome) in the new pediatric Centers for Disease Control and Prevention classification during the first year of life, according to clinical, immunological, and virological findings at birth. RESULTS: The risk of category C manifestations at 12 months was significantly higher when an infected newborn had liver and/or spleen enlargement and/or adenopathies (38.1% vs 15.1%; relative risk [RR], 2.5; 95% confidence interval [CI], 1.4 to 6.0; P<.02) or a low proportion (<30%) of CD4+ cells at birth (45.5% vs 15.0%; RR, 3.0; 95% CI, 1.4 to 6.4; P<.005). Similarly, HIV-1 culture and/or polymerase chain reaction positivity during the first week of life was associated with a higher risk of the early, severe form of HIV infection (26.4% vs 9.3%; RR, 2.8; 95% CI, 1.3 to 6.1; P<.006). In case of positive antigenemia at birth, the risk was 50.0% vs 14.4% (RR, 3.5; 95% CI, 1.9 to 6.2; P<.001). These parameters, determined at birth, were strongly interrelated and could reflect active disease onset in utero in some cases of early, severe HIV-1 disease in childhood. CONCLUSIONS: These prognostic markers, particularly virological parameters, are of value in monitoring children infected by HIV and might serve as a basis for early therapeutic intervention.

AIDS Serodiagnosis↗

Testing for in utero human immunodeficiency virus infection with fetal blood sampling.

OBJECTIVE: Our purpose was to evaluate the potential of midtrimester fetal blood sampling to detect in utero human immunodeficiency virus type 1 infection. STUDY DESIGN: Ultrasonographically guided fetal blood sampling was performed before pregnancy termination in 28 women infected with human immunodeficiency virus type 1. Mean gestational age was 22 weeks (range 15 to 29 weeks). Samples were tested for human immunodeficiency virus with undissociated p24 antigen and deoxyribonucleic acid polymerase chain reaction or viral isolation by cell culture. After terminations fetal thymuses were also tested for human immunodeficiency virus infection by polymerase chain reaction. Polymerase chain reaction was also performed on maternal cells to confirm that the primer pairs used were able to detect human immunodeficiency virus type 1 strains present. RESULTS: All fetal blood samples had negative results by p24 antigen and polymerase chain reaction or virus culture and all fetal thymuses were negative by polymerase chain reaction. CONCLUSION: Early in utero human immunodeficiency virus infection appears infrequent, supporting the hypothesis that mother-to-child transmission predominantly occurs late in pregnancy. Therefore midtrimester prenatal diagnosis is not currently of use to women in making reproductive decisions.

Antigens, Viral↗

Road traffic offending, stress, age, and accident history among male and female drivers.

This paper draws on data gathered during a larger study of driving behaviour to explore possible connections between stress, offending against the traffic laws, and accident rates, and gives particular attention to comparisons between male and female drivers. Data were gathered from 422 drivers by a postal questionnaire, and further measures of stress were obtained during semi-structured interviews with a specially selected subset of 66 of them. Analyses of variance investigated links between offending rates, accident history, and up to seven measures of stress, taking age and gender into account. In the results accident history, although positively related to offending, played little part in links involving stress variables. The principal findings were that (a) stress, both on and off the road, was positively associated with offending among both male and female drivers, and (b) although females overall offended less than males, females experienced more stress than males whatever their level of offending. One possible interpretation of these results is suggested by the feminist literature, which could account for both the higher levels of stress and lower levels of offending found among women drivers. However, there is unlikely to be a clear-cut gender divide in offending-stress relationships, and some small groups of female drivers in the study behaved like male ones. It is suggested that people's driving reflects their lifestyles, and that women drivers' patterns of offending and stress will resemble those of male drivers to the extent that their lives and concerns are similar to men's. It is concluded that this position warrants further research.

Accidents, Traffic↗

Lack of screening test sensitivity during HIV-1 non-subtype B seroconversions.

OBJECTIVE: To evaluate the serological consequences of HIV-1 group M diversity we studied the ability of screening tests to detect anti-HIV antibodies in early seroconverters infected by different HIV subtypes. SETTING: Virology Department, Bichat-Claude Bernard Hospital, Paris, France. DESIGN AND METHODS: Symptomatic patients with serial samples and with infective strains characterized by heteroduplex mobility assay. In each case, two sera were selected. The first (pre-seroconversion sample) was the last p24 antigen-positive/Western blot-non-reactive sample. The second (seroconversion sample) was the first Western blot-reactive sample. One second-generation enzyme immunoassay (EIA; Abbott) based on anti-human immunoglobulin (Ig) G-conjugate and three third generation EIA (Abbott; Enzygnost; Genscreen) based on the double antigen sandwich principle, detecting IgM and IgG, were used. RESULTS: Ten patients had subtype B strains and nine had non-B strains (seven were A, one E and one G). The Abbott third-generation test was more sensitive than the second generation test for pre-seroconversion subtype B samples (nine versus four out of 10; P < 0.05), but not for non-B subtypes; only two of the nine non-B sera tested were positive by both EIA. Positivity rates and optical densities differed (P < 0.05) between B and non-B subtypes in all third-generation EIA. There was no significant difference between the subtype B and non-B groups with regard to the interval between the pre-seroconversion sample and the seroconversion sample (subtype B, 6.7 +/- 2.6 days; non-B, 5.2 +/- 1.7 days). No significant difference in positivity rates and optical densities were found between B and non-B subtypes in these seroconversion samples. CONCLUSION: The shorter time since HIV infection required for sera to become reactive in third-generation EIA screening tests is due to better sensitivity for subtype B strains only. These results stress the importance of strict donor selection, the need to test screening kits against large panels of all subtypes, and the place of p24 antigen testing in closing the window of seroconversion.

Antibodies, Viral↗

Multicenter evaluation of new double-antigen sandwich enzyme immunoassay for measurement of anti-human immunodeficiency virus type 1 and type 2 antibodies.

A new enzyme immunoassay (EIA), the Cobas Core Anti-HIV-1/HIV-2 EIA DAGS (also referred to as Roche DAGS), for the detection of antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2 was evaluated in four centers. The assay is based on the double-antigen sandwich (DAGS) format, which enables the detection of all classes of antibodies. The antigens consist of recombinant proteins in their native conformation and of synthetic peptides. Of a total of 5,836 negative serum samples, including 95 samples likely to produce false reactivities, 6 were false positive, resulting in a specificity of 99.9%. None of 35 sera that were from noninfected individuals but contained p24-cross-reacting antibodies as revealed by Western blot (immunoblot) analysis were reactive by the Roche DAGS assay. In samples from individuals infected with HIV-1 group M (n = 499) and HIV-2 (n = 200), the sensitivity of the assay was 100%. Although containing antigens with sequences from subtype B only, the assay was also able to correctly identify with high optical density/cutoff ratios samples from subjects infected with HIV-1 subtype O (n = 10). In 17 of 19 seroconversion panels tested, the assay detected the presence of HIV-1 antibodies as early as another sandwich EIA. Eight of these panels were also analyzed by an indirect second-generation assay, which detected antibodies 2 to 10 days later than did the DAGS assay under evaluation. The excellent specificity and sensitivity of the new Cobas Core Anti-HIV-1/HIV-2 EIA DAGS are the result of the DAGS format as well as of the native, naturally folded form of the recombinant protein used as the gag antigen.

Female↗

Psychological factors in the diagnosis and pathogenesis of stiff-man syndrome.

Retrospective psychological evaluation of nine patients with stiff-man syndrome (SMS), seven of whom evidenced autoimmune disease, revealed a characteristic set of psychological symptoms or features: Major stressful life events preceded the development of permanent symptoms by 6 months or less (seven patients); transient motor symptoms occurred in emotionally distressing situations months or even years before the onset of a permanent motor deficit (five patients); after onset, similar situations specifically precipitated or augmented stiffness and spasms (five patients). We also found task-specific fear resembling agoraphobia (six patients) and loss or invalidation of one or both parents, or loss of home, in childhood (seven patients). Eight patients were initially misdiagnosed as having psychogenic movement disorder. We conclude that the common misdiagnosis of SMS as a psychogenic movement disorder is due to the compelling association of a set of salient psychological features, bizarre and fluctuating motor symptoms, and lack of approved neurologic signs.

Adult↗

Fluorometric detection of HIV-1 genome through use of an internal control, inosine-substituted primers, and microtiter plate format.

We describe a PCR-based fluorometric assay for the detection of the HIV-1 genome. This technique consists of a reverse hybridization with oligonucleotide probes covalently coated onto a microtiter plate as a solid support. Several improvements to the PCR amplification and detection steps gave greater sensitivity and specificity for HIV-1 screening and resulted in a convenient and rapid technique. False-positive results were avoided by using uracyl DNA glycosylase. False-negative results from the presence of PCR inhibitors were detected by coamplifying an internal control with the viral sequence. False-negative results from viral genome variability were limited by using two pairs of primers and by incorporating inosine at the primer positions corresponding to viral polymorphic nucleotides. Furthermore, the hybridization buffer and enzymatic reaction were optimized to increase the assay's sensitivity. The sensitivity and specificity of the fluorometric detection were similar to those of radioisotopic oligonucleotide solution hybridization; however, hands-on time was reduced, and the use of radioactivity was eliminated. We have used this technique routinely on 115 samples and obtained 100% specificity and high sensitivity (only one false-negative result) according to viral culture and (or) serological status of the patients.

Acquired Immunodeficiency Syndrome↗

[Virulence of human immunodeficiency virus].

Virulence is relative capacity of a virus, compared to other closely related viruses, to produce disease in a host. Viral strains considered as virulent have been described in HIV-1 infected patients. They are characterized in vitro by enhanced cellular host range, rapid kinetic of replication and increased capacity of syncytium induction. Some genetic modification of the V3 loop in the envelope gene have been associated with the emergence of these strains. But at AIDS diagnosis, and even at the terminal stage of AIDS, only about half of the patients harbour syncytium inducing variants. There are much evidence for continuous viral replication throughout all stages of HIV-1 infection. There is no viral latency state in the natural HIV infection. This increasing viral burden might have a pivotal role in the pathogenesis of HIV disease. HIV-2 is less pathogenic than HIV-1. The nature of the viral determinants responsible for this reduced virulence remains unknown. In the simian immunodeficiency virus model, virulent and avirulent strains have been described and the nef gene seems to have a critical role in pathogenicity.

Acquired Immunodeficiency Syndrome↗

Reactivity of five anti-HIV-1 subtype O specimens with six different anti-HIV screening ELISAs and three immunoblots.

Five anti-subtype O specimens were tested by anti-HIV-1/2 screening and confirmatory assays. They can be divided into three specimens, reactive with all ELISAs, independent of the nature of the antigen (recombinant proteins or peptides) and test configuration (indirect ELISA or double antigen/sandwich ELISA). One specimen was not detected by one peptide based ELISA. One specimen was only recognized by two ELISAs and should be considered as a marker sample for the weakness of currently used ELISAs with anti-subtype O. Three different immunoblot assays available commercially detected two of the specimens with a major binding of gp160 and other viral bands, especially the integrase and reverse transcriptase. Another two specimens lacked reactivity with glycoproteins almost completely, but showed some staining with the enzymes of HIV, and would most probably be interpreted as indeterminate. The fifth specimen, which was also missed by most of the ELISAs, had very faint staining of the gp160 and a very weak staining of p24, and would most probably be interpreted as negative. Adaption of currently available tests to anti-subtype O is needed for the future reliability of anti-HIV diagnostic reagents.

AIDS Serodiagnosis↗

Immunocytochemical study of lampbrush chromosomes of the urodele Pleurodeles waltl: axial granules are recognized by the mitosis-specific monoclonal antibody MPM-2.

The lampbrush chromosomes of the urodele Pleurodeles waltl have been studied using the mitosis-specific monoclonal antibody MPM-2. Immunofluorescence studies revealed that MPM-2 stains structures associated with axial granules, numerous other chromomeres, telomeres and certain chiasmata. These structures showed a negative reaction with the anti-DNA monoclonal antibody AC-30-10. In course of meiotic condensation of the chromosomes, in growing and maturating oocytes, the number of such structures associated with the chromosome axis was found to diminish progressively. These granular structures have been found to be formed by fine fibrils about 5 nm in diameter. Immunogold labeling confirmed the results of immunofluorescence studies. MPM-2 was also found to stain two other types of structures observed in association with the lampbrush chromosome axis in P waltl, viz the sphere organelle (only in later stages of oogenesis) and the structure known as 'M' which is singular to this material.

Animals↗

Reduced capacity of antibodies from patients infected with human immunodeficiency virus type 1 (HIV-1) group O to neutralize primary isolates of HIV-1 group M viruses.

Neutralizing antibody patterns in sera of persons infected with human immunodeficiency virus type 1 (HIV-1) groups M and O to their homologous and heterologous primary isolates were determined in a peripheral blood mononuclear cell-based neutralization assay and correlated with their ability to bind to V3 loop synthetic peptides. Most HIV-1 group M sera (9/16) neutralized HIV-1 group O viruses, whereas fewer group O sera (3/13) only weakly neutralized HIV-1 group M viruses. Group M sera neutralizing HIV-1 group O viruses neutralized other HIV-1 group M viruses with titers of 1:10-1:1280. V3 loop binding capacity of sera did not reflect their neutralizing capacity of the homologous isolate. Despite the reduced neutralizing capacity of group O-infected patients' sera to group M viruses, some group M-infected patients' sera neutralized both HIV-1 group M and O isolates, suggesting that they share some conserved neutralizing epitopes.

Acquired Immunodeficiency Syndrome↗

Variability of human immunodeficiency virus type 1 group O strains isolated from Cameroonian patients living in France.

Human immunodeficiency virus type 1 (HIV-1) nucleotide sequences encoding p24Gag and the Env C2V3 region were obtained from seven patients who were selected on the basis of having paradoxical seronegativity on a subset of HIV enzyme-linked immunosorbent assay detection kits and having atypical Western blot (immunoblot) reactivity. Sequence analyses showed that all of these strains were more closely related to the recently described Cameroonian HIV isolates of group O (HIV-1 outlier) than to group M (HIV-1 major). All seven patients had Cameroonian origins but were living in France at the time the blood samples were taken. Characterization of a large number of group M strains has to date revealed eight distinct genetic subtypes (A to H). Genetic distances between sequences from available group O isolates were generally comparable to those observed in M intersubtype sequence comparisons, showing that the group O viruses are genetically very diverse. Analysis of sequences from these seven new viral strains, combined with the three previously characterized group O strains, revealed few discernable phylogenetic clustering patterns among the 10 patients' viral sequences. The level of diversity among group O sequences suggests that they may have a comparable (or greater) age than the M group sequences, although for unknown reasons, the latter group dispersed first and is the dominant lineage in the pandemic.

Acquired Immunodeficiency Syndrome↗