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Biomedical subjects

F Simon

Publications and source records attributed to F Simon.

At least 55 records · Page 3Linked to original sources

Phylogenetic analysis of 49 newly derived HIV-1 group O strains: high viral diversity but no group M-like subtype structure.

We assess the genetic relationships between 49 HIV-1 group O strains from 24 and 25 patients living in Cameroon and France, respectively. Strains were sequenced in four genomic regions: gag (p24) and three env regions (C2-V3, gp41, and for 22 C2-gp41). In each of the genomic regions analyzed, the genetic diversity among the group O strains was higher than that exhibited by group M. We characterize three major group O phylogenetic clusters (O:A, O:B, and O:C) that comprised the same virus strains in each of the genomic regions analyzed. The majority of strains cluster in O:A, a cluster previously identified by analysis of pol and env sequences. Group O recombinants were also identified. Importantly, the distinction between these three major group O clades was weak compared to the strong clustering apparent in the global group M phylogenetic tree that led to the identification of subtypes. Thus, these clusters of group O viruses should not be considered as equivalent to the group M subtypes. This difference between the pattern of group O and the global group M diversity, both taking into account the pandemic status of the group M subtypes and the comparatively small number of group O-infected individuals (the majority being from Cameroon), indicates that the group O phylogeny primarily represents viral divergence in the Cameroon region, analogous to group M viral diversity present in the Democratic Republic of Congo.

Adolescent↗

Diamond-like carbon coatings with Ca-O-incorporation for improved biological acceptance.

Diamond-like carbon (DLC) coatings were modified by doping the thin films with Ca-O compounds. Raman spectroscopy indicates growth of sp(2)-hybridised, ordered regions in size and/or number within the amorphous carbon-hydrogen network as a result of the Ca-O-incorporation. CaCO(3) was identified by X-ray induced photoelectron spectroscopy. Proliferation and morphology of L929 mouse fibroblasts reveal improved biocompatibility of Ca-O-modified DLC.

Animals↗

Differential expression of IgG Fc binding protein (FcgammaBP) in human normal thyroid tissue, thyroid adenomas and thyroid carcinomas.

The genetic events involved in thyroid carcinogenesis are still incompletely understood. Several rearrangements and mutations of oncogenes have been implicated in the development of thyroid papillary carcinomas, follicular adenomas and carcinomas. However, none of these molecular alterations is suitable either as a general marker for the diagnosis of thyroid carcinomas or to differentiate between thyroid follicular adenomas and carcinomas. In order to identify new genes with altered expression which could serve as such markers, we analyzed RNA from thyroid tumor and normal tissue using a novel technique called restriction-mediated differential display. Several differentially expressed genes were identified, including the gene for IgG Fc binding protein (FcgammaBP). Differential expression of FcgammaBP was confirmed by quantitative real-time RT-PCR. Our experiments showed that IgG Fc binding protein (FcgammaBP) is differentially expressed in normal thyroid tissue, thyroid adenomas and thyroid carcinomas. While the FcgammaBP gene is constitutively expressed in normal thyroid tissue, its expression is significantly increased in follicular thyroid adenomas and significantly decreased in papillary and follicular thyroid carcinomas. Thus, measurement of the expression levels of FcgammaBP in thyroid biopsies might help to make the otherwise difficult distinction between a thyroid follicular adenoma and a follicular carcinoma.

Adenoma↗

[Cardiovascular diseases and HIV infection: study of 79 cases at the National Hospital of Ouagadougou (Burkina Faso)].

Cardiovascular diseases during HIV infection are frequent and serious. The aim of this first study in Burkina Faso was to analyse cardiovascular affections in HIV-positive African patients, admitted to the adult cardiology unit of the Yalgado Ouedraogo National Hospital of Ouagadougou. We conducted a retrospective study of consecutive cases admitted to the cardiology unit between 1 January 1993 and 31 March 1999. The inclusion criteria were: progressive heart affection, positive HIV serology, and the absence of cardiovascular antecedents or pathology. We studied age, sex, clinical and complementary parameters (electrocardiogram, thoracic radiography, electrocardiography), treatment and evolution. 79 black Africans were included, 44 men and 35 women. The mean age was 36.3 +/- 9.8 years. The clinical presentation was principally heart failure (79% of cases). Myocarditis or cardiomyopathy was found in 45 cases (57%); isolated pericarditis--in 25 cases (32%); pulmonary hypertension--in 4 cases (5%); pulmonary embolism--in 3 cases; and myocardial infarction--in 2 cases. According to the Atlanta CDC classification for HIV infection, 70% of the patients where in stage C. The overall hospital mortality rate was 15%. Cardiac lesions were present principally with myocardium and pericardium, with high specific mortality.

Adult↗

HIV type 1 genetic diversity and genotypic drug susceptibility in the Republic of Moldova.

HIV-1 genetic diversity and, for the first time, genotypic drug susceptibility was investigated for strains circulating in the Republic of Moldova (of the former Soviet Union). Eighty-three samples from adults recently infected by intravenous drug use (IDU) (n = 60), heterosexual contact (n = 8), and from blood donors (n = 15) that tested positive from 1997 to 1998, and originating from different regions of Moldova were serotyped. By group-specific and subtype-specific peptide ELISA, patients were infected by serotype A (n = 65), serotype B (n = 1), or were nontypable (n = 17). Heteroduplex mobility assay (HMA) confirmed 11 subtype A and the one subtype B infection. Analyses of pol and env sequences for six of the IDUs confirmed that they were infected with subtype A strain. These strains clustered tightly with subtype A strains isolated from the former Soviet Union in phylogenetic analysis. No mutations associated with drug resistance were detected. The Republic of Moldova is culturally more closely related to Romania (where subtype F dominates the epidemic), but depends economically on Russia (where subtype A is established among IDUs). Thus, our results suggest that the spread of HIV in this region is driven by drug networks rather than being due to cultural similarities.

Adolescent↗

Anisotropy of superconducting MgB2 as seen in electron spin resonance and magnetization data.

We observed the conduction electron spin resonance (CESR) in fine powders of MgB2 both in the superconducting and normal states. The Pauli susceptibility is chi(s) = 2.0 x 10(-5) emu/mole in the temperature range of 450 to 600 K. The spin relaxation rate has an anomalous temperature dependence. The CESR measured below T(c) at several frequencies suggests that MgB2 is a strongly anisotropic superconductor with the upper critical field, H(c2), ranging between 2 and 16 T. The high-field reversible magnetization data of a randomly oriented powder sample are well described assuming that MgB2 is an anisotropic superconductor with H(ab)(c2)/H(c)(c2) approximately 6-9.

Journal Article↗

Synthetic peptide strategy for the detection of and discrimination among highly divergent primate lentiviruses.

We developed a simple, rapid, inexpensive, and highly sensitive and specific strategy for the detection and lineage differentiation of primate lentiviruses (PIV-ELISA). It is based on the use of two indirect ELISA methods using synthetic peptides mapping the gp41/36 region (detection component) and the V3 region (differentiation component) of four lentivirus lineages, namely SIVcpz/HIV-1 (groups M, O, N, and SIVcpz-gab), SIVmnd, SIVagm, and SIVsm/SIVmac/HIV-2. This strategy was evaluated with panels of sera originating from both humans and nonhuman primates. The human reference panel consisted of 144 HIV Western blot (WB)-positive sera in which the corresponding virus had been genotyped (HIV-1: 72 group M, 28 group O, and 6 group N; HIV-2: 21 subtype A and 10 subtype B; and 7 HIV-1+2) and 105 HIV WB-negative samples. The nonhuman primate reference panel consisted of 24 sera from monkeys infected by viruses belonging to the four lineages included in the PIV-ELISA strategy (5 chimpanzees, 5 macaques, 8 mandrills, and 6 vervets) and 42 samples from seronegative animals. Additional field evaluation panels consisted of 815 human sera from Gabon, Cameroon, and France and 537 samples from 25 nonhuman primate species. All the samples from the two reference panels were correctly detected and discriminated by PIV-ELISA. In the human field evaluation panel, the gp41/36 component correctly identified all the test samples, with 98% specificity. The V3 component discriminated 206 HIV-1 group M, 98 group O, 12 group M+O, and 128 HIV-2 sera. In the primate field evaluation panel, both gp41/36 and V3 detected and discriminated all the WB-positive samples originating from monkeys infected with SIVcpz, SIVagm-ver, SIVmnd-1, SIVmnd-2, SIVdrl, or SIVsun. These results were confirmed by genotyping in every case. Four SIV-infected red-capped mangabeys (confirmed by PCR) were correctly identified by gp41/36, but only two reacted with the V3 peptides in the absence of a specific SIVrcm V3 peptide. Addition of a V3 SIVrcm peptide discriminated all the SIVrcm-positive samples. Fourteen Papio papio samples were positive for SIVsm gp 36 and by WB, but negative by PCR, whereas three Papio cynocephalus samples were positive by gp41/36 but indeterminate by WB and negative by PCR. This combined ELISA system is thus highly sensitive and specific for antibodies directed against HIV and SIV. In addition, the V3-based serotyping results always agreed with genotyping results. This method should prove useful for studies of lentivirus prevalence and diversity in human and nonhuman primates, and may also have the potential to detect previously undescribed SIVs.

Amino Acid Sequence↗

Zidovudine genotypic resistance in HIV-1-infected newborns in the French perinatal cohort.

A retrospective study was set up to investigate the frequency of zidovudine (ZDV)-resistant HIV-1 in infected newborns after ZDV prophylaxis in the French Perinatal Cohort study. Nucleotide sequence analysis was carried out from 34 infants' isolates and 18 maternal plasma samples. Mutations related to ZDV resistance were found in the HIV-1 reverse transcriptase in 7 of 34 children (20%). Evidence of mother-child transmission of ZDV-resistant HIV-1 was found in 4 cases. Phylogenetic analysis showed that 14 of 34 HIV-1 isolates from the infants belonged to non-B subtypes. The presence of ZDV resistance-encoding mutations in the newborn isolates was associated with a longer total duration of exposure to ZDV. In a context of a wide HIV-1 variability, ZDV resistance can be one of the factors contributing to mother-child transmission.

Anti-HIV Agents↗

Variability of human immunodeficiency virus type 2 (hiv-2) infecting patients living in france.

To determine the prevalence of human immunodeficiency virus type 2 (HIV-2) subtypes circulating in France and to identify possible relationships between these subtypes and pathogenesis, we studied 33 HIV-2-infected patients living in France. HIV-2 DNA was directly amplified from peripheral blood mononuclear cells by nested PCR with specific HIV-2 env primers, and the env gene was sequenced. The serological consequences of antigenic variability were studied by using a panel of peptides and by Western blotting. Phylogenetic analysis classified the 33 HIV-2 strains as subtype A (n = 23) or B (n = 10). There were no significant clinical or epidemiological differences between patients infected with either of these two subtypes. There was some evidence for geographical clustering. Subtype A strains from patients originating from the Cape Verde Islands and Guinea Bissau clustered together. The majority of patients infected with subtype B strains originated from the Ivory Coast or Mali. Strains from patients originating in Mali also clustered in subtype A but distinctly from the Cape Verde or Guinea Bissau strains. The subtype B strains showed greater diversity and included some highly divergent strains relative to those previously characterized. The V3 loop of HIV-2 subtypes A and B was found to be quite conserved in comparison with HIV-1. A strong HIV-2 subtype B serological cross-reactivity was found on HIV-1 env antigen by Western blot mostly in the gp41 transmembrane glycoprotein. This could partly explain the double HIV-1 and HIV-2 reactive profiles found in countries where HIV-2 subtype B is prevalent.

Adult↗

On the new anatomical nomenclature.

The present paper is concerned with the linguistic aspect of the new anatomical nomenclature (Terminologia Anatomica 1998). Orthographic, morphological, syntactic, lexical, and terminological comments are presented. In the authors' opinion, shortcomings might have been effectively avoided by cooperation with linguists.

Anatomy↗

Ezrin-radixin-moesin-binding phosphoprotein 50 is expressed at the apical membrane of rat liver epithelia.

Ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 (EBP50) and NHE3 Kinase A regulatory protein (E3KARP) are membrane-cytoskeleton linking proteins that utilize 2 PSD-95/DIg/ZO-1 (PDZ) domains and an ERM binding site to coordinate cyclic adenosine monophosphate (cAMP)-regulated ion transport in a number of distinct epithelia. ERM family members serve to anchor EBP50 and E3KARP to the actin cytoskeleton and sequester protein kinase A (PKA) to these protein complexes. In hepatocytes and cholangiocytes, the epithelial cells of the bile secretory unit, cAMP-activated PKA stimulates secretion and bile formation, but the molecular mechanisms, including the potential contribution of EBP50 and E3KARP, remain undetermined. The present studies evaluated the comparative expression and localization of EBP50 and E3KARP in rat hepatocytes and cholangiocytes. Complementary DNAs encoding rat EBP50 and E3KARP were identified by reverse transcription-polymerase chain reaction in both epithelial cell types and subsequently sequenced. Northern and Western analysis showed the presence of EBP50 messenger RNA and protein in both hepatocytes and cholangiocytes. Confocal immunofluorescence revealed EBP50 was concentrated at the apical domain of both cell types. E3KARP was also expressed in cholangiocytes but had a distinct cytoplasmic/nuclear distribution. In dominant-negative transfection studies, patch clamp analysis of Mz-ChA1 cholangiocarcinoma cells showed that expression of the PDZ1 domain of EBP50 selectively decreased the endogenous cAMP-mediated Cl secretory response. The apical expression of EBP50, presence of specific ERM proteins, and functional effects of PDZ1 expression on cholangiocyte secretion suggest EBP50 is positioned to contribute to the organization and regulation of bile secretory proteins in both hepatocytes and cholangiocytes.

Amino Acid Sequence↗

V3 serological subtyping of human immunodeficiency virus type 2 infection is not relevant.

V3 enzyme immunoassays have been shown to discriminate effectively between human immunodeficiency virus type 1 (HIV-1) subtypes. The aim of this study was to investigate the feasibility of V3 serotyping for HIV-2 infection. We serotyped 29 sera with three peptides, corresponding to the V3 loop of subtypes A, B, and D of HIV-2. Sera were collected from HIV-2-infected patients, whose infecting strains were sequenced and subjected to phylogenetic analysis. Our results indicate that HIV-2 serotyping using V3 peptides is not relevant. V3 serotyping data were not consistent with genotyping results. The V3-A and V3-D peptides displayed poor discrimination, and the V3-B peptide was not representative of circulating viruses. Comparison of amino acid sequences and serotype reactivities demonstrated the importance of positions 309 and 314, located on either side of the tip of the V3 loop, in antibody binding.

Amino Acid Sequence↗

Quantification of proviral load of human immunodeficiency virus type 2 subtypes A and B using real-time PCR.

We have developed and evaluated a new method to quantify human immunodeficiency virus type 2 (HIV-2) proviral DNA based on LightCycler real-time PCR. The assay has a detection limit of 5 copies/10(5) peripheral blood mononuclear cells (PBMC) and is insensitive to HIV-2 strain variability: HIV-2 subtypes A and B are both recognized and quantified. The intra- and interassay coefficients of variation range from 16 to 40% for high provirus concentrations (5 x 10(5) copies) and from 41 to 39% for low concentrations (5 copies). We used this method to compare the proviral DNA load and viral RNA load in plasma with clinical and immunological status for 29 patients infected by HIV-2 (subtype A in 17 and subtype B in 12). The proviral load (median, 201 copies/10(5) PBMC) was similar to that reported for HIV-1 infection. The median proviral loads did not correlate with the CD4(+) cell count categories and were as follows for CD4(+) cell counts of >400, 200 to 400, and <200 cells/mm(3), respectively: 121 copies/10(5) PBMC (n = 8; range, <5 to 712 copies/10(5) PBMC); 114 copies/10(5) PBMC (n = 9; range, <5 to 1,907 copies/10(5) PBMC); and 285 copies/10(5) PBMC (n = 12; range, 53 to 2,524 copies/10(5) PBMC). Proviral load did not correlate with plasma HIV-2 RNA positivity. As HIV-2 is considered to replicate less efficiently than HIV-1, these high proviral loads might be explained by the proliferation of infected cells.

Adult↗

Wild Mandrillus sphinx are carriers of two types of lentivirus.

Mandrillus sphinx, a large primate living in Cameroon and Gabon and belonging to the Papionini tribe, was reported to be infected by a simian immunodeficiency virus (SIV) (SIVmndGB1) as early as 1988. Here, we have identified a second, highly divergent SIVmnd (designated SIVmnd-2). Genomic organization differs between the two viral types; SIVmnd-2 has the additional vpx gene, like other SIVs naturally infecting the Papionini tribe (SIVsm and SIVrcm) and in contrast to the other SIVmnd type (here designated SIVmnd-1), which is more closely related to SIVs infecting l'hoest (Cercopithecus lhoesti lhoesti) and sun-tailed (Cercopithecus lhoesti solatus) monkeys. Importantly, our epidemiological studies indicate a high prevalence of both types of SIVmnd; all 10 sexually mature wild-living monkeys and 3 out of 17 wild-born juveniles tested were infected. The geographic distribution of SIVmnd seems to be distinct for the two types: SIVmnd-1 viruses were exclusively identified in mandrills from central and southern Gabon, whereas SIVmnd-2 viruses were identified in monkeys from northern and western Gabon, as well as in Cameroon. SIVmnd-2 full-length sequence analysis, together with analysis of partial sequences from SIVmnd-1 and SIVmnd-2 from wild-born or wild-living mandrills, shows that the gag and pol regions of SIVmnd-2 are closest to those of SIVrcm, isolated from red-capped mangabeys (Cercocebus torquatus), while the env gene is closest to that of SIVmnd-1. pol and env sequence analyses of SIV from a related Papionini species, the drill (Mandrillus leucophaeus), shows a closer relationship of SIVdrl to SIVmnd-2 than to SIVmnd-1. Epidemiological surveys of human immunodeficiency virus revealed a case in Cameroon of a human infected by a virus serologically related to SIVmnd, raising the possibility that mandrills represent a viral reservoir for humans similar to sooty mangabeys in Western Africa and chimpanzees in Central Africa.

Amino Acid Sequence↗