Search PubMed⌕ Search

Biomedical subjects

P Roques

Publications and source records attributed to P Roques.

At least 37 records · Page 2Linked to original sources
PubMed1999

An unusual HIV type 1 env sequence embedded in a mosaic virus from Cameroon: identification of a new env clade. European Network on the study of in utero transmission of HIV-1.

An atypical HIV-1 strain (CAM001) was identified in a pregnant Cameroonian woman in 1995. HMA subtyping of the env region was unsuccessful, and sequence analyses were performed. Unique sequence motifs were found at the V3 tip (GAGRALHA and GAGRAWIHA), and phylogenetic studies showed that the env C2-V5 sequence branched within group M but remained distinct from all known HIV-1 subtypes, while p17 gag branched with the subtype F sequences. Four other HIV group M viruses, undetermined by HMA, of African origin were found to cluster with CAM001 in the C2-V5 sequences. With the BLAST method, we found in databases three strains whose V3 sequences also clustered with CAM001. These unusual env sequences from eight HIV-1 strains derived from Cameroon formed a separate cluster in HIV-1 group M, which we designated k.

Amino Acid Sequence↗
PubMed1999

Vertical transmission of HIV: parameters which might affect infection of placental trophoblasts by HIV-1: a review. Biomed Group on the Study of in Utero Transmission of HIV 1.

PROBLEM: To understand the mechanisms preventing and/or facilitating maternofetal transmission of human immunodeficiency virus (HIV)-1 across the placenta during pregnancy. METHODS OF STUDY: Current experimental data were reviewed. RESULTS AND CONCLUSIONS: The data about the production of cytokines by placental cells and explants, taken together with information indicating selective passage of certain HIV-1 variants across the placental trophoblast, suggest an intricate regulatory network operating at the fetomaternal interface. The data show a differential differentiation of early and late trophoblasts, as far as HIV entry routes are concerned. We believe this explains the relative predominance of the early infection window, as far as in utero infection is concerned. Whether such a differentiation state can be transiently induced on term placental trophoblasts by several differentiation agents, including cytokines, is being investigated. Whatever the results may be, it is obvious that infection of placental cells is an excellent model of passage infection by HIV of/through a mucosal barrier.

Chemokines↗
PubMed1998

Selective quasispecies transmission after systemic or mucosal exposure of macaques to simian immunodeficiency virus.

Sexual transmission is the major cause of the AIDS epidemic. For the development of new antiviral and vaccine strategies, we therefore need to understand the mechanisms by which lentiviruses cross the mucosal barrier and the subsequent pathogenic consequences. For this purpose, experimental approaches are greatly facilitated by the development of relevant animal models. In this study, macaques were inoculated intravenously, intrarectally, or intravaginally with a pathogenic cell-free isolate of SIVmac251. Patterns of virological and immunological events significantly differed between vaginally (transient viremia, late seroconversion) and intravenously or intrarectally inoculated monkeys (persistent viremia and early seroconversion). Two weeks after infection, analysis of the env gene nucleotide sequences of proviruses recovered from PBMCs demonstrated that most of the differences were observed in the V1 loop. Three viral variants were specifically associated with vaginal transmission, whereas no such selection was evidenced after intravenous or intrarectal transmissions. These results are in favor of specific mechanisms associated with vaginal transmission, implicating viral envelope structure.

Amino Acid Sequence↗
PubMed1998

Identification of a new human immunodeficiency virus type 1 distinct from group M and group O.

A highly divergent HIV-1 isolate, designated YBF 30, was obtained in 1995 from a 40-year-old Cameroonian woman with AIDS. Depending on the genes studied, phylogenetic analysis showed that YBF30 branched either with SIVcpz-gab or between SIVcpz-gab and HIV-1 group M. The structural genes and tat, vpr, and nef of YBF30 are approximately equidistant from those of HIV-1 group M and SIVcpz-gab. In contrast, vif and rev are closer to HIV-1 group M, and vpu is highly divergent. Using a YBF30 V3 loop peptide enzyme immunoassay, we screened 700 HIV-1-positive sera collected in Cameroon; three reacted strongly with the YBF30 peptides and one was confirmed as being related to YBF30 by genetic analysis of a pol fragment. YBF30 is as distinct from SIVcpz-gab as it is from HIV-1 group M and can thus be considered as the prototype strain of a new human immunodeficiency virus group.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Modulations of cytokine expression in pregnant women.

PROBLEM: Although the overall anti-infectious and anti-parasitic immunity of parous women appears normal, several aspects of maternal cell-mediated and humoral immunity are altered during pregnancy. This has been suggested to occur via preferential local and systemic secretion of Th-2 type cytokines, which down-regulate or prevent secretion/action of Th-1 type cytokines, in animals as well as in humans. METHOD: To evaluate the influence of gestation on the maternal immune system, we have measured, in pregnant women, the mRNAs coding for several cytokines (TNF alpha, IFN gamma, GM-CSF, IL-1 beta, IL-2, IL-4, IL-6, and IL-10) in peripheral blood mononuclear cells, by use of semi-quantitative RT-PCR. RESULTS: Our results show significant modulations of IFN gamma, IL-1 beta, IL-4, and IL-6 genes expression especially during the third trimester and near parturition. CONCLUSION: Cytokine expression is thus finely tuned in peripheral blood during pregnancy, in a previously unexpected complex pattern, related to gestational stage.

Cohort Studies↗
PubMed1996

Superinfection of HIV-2-preinfected macaques after rectal exposure to a primary isolate of SIVmac251.

To test the protection afforded by a weakly pathogenic HIV-2 isolate against the superinfection or development of SIV-induced disease, we intrarectally challenged six HIV-2-preinfected rhesus monkeys with a pathogenic isolate of SIVmac251. At the time of SIV challenge, none of these HIV-2-infected animals was positive for virus isolation, p27-Gag antigenemia, or HIV-2 provirus detection in PBMCs or peripheral lymph nodes. However, all monkeys exhibited anti-HIV-2 antibody titers ranging from 10(2) to 10(3). Neutralizing antibodies against the challenge SIV strain were also detected in two animals. After rectal exposure to SIVmac251, five of the six HIV-2-preinfected macaques were superinfected. SIVmac251 DNA sequences were detected repeatedly in the PBMCs of the five superinfected animals and the two controls, whereas no HIV-2 provirus was detected for 14 months postchallenge. The one monkey that resisted superinfection was negative for all SIV infection criteria. This monkey exhibited the highest anti-SIV ELISA and cross-neutralizing antibody titers on the day of SIV challenge. Preinfection with a weakly pathogenic HIV-2 ROD isolate protected one of six macaques from infection with the closely related pathogenic SIVmac251 isolate, but no protection from the progression of disease was evidenced in the other five.

AIDS Vaccines↗
PubMed1996

Complete analysis of the presenilin 1 gene in early onset Alzheimer's disease.

The presenilin 1 gene has recently been identified as the locus on chromosome 14 which is responsible for a large proportion of early onset, autosomal dominantly inherited Alzheimer's disease (AD). We have elucidated the intron/exon structure of the gene and designed intronic primers to enable direct sequencing of the entire coding region (10 exons) of the presenilin gene in a large number of families. This strategy has enabled us to find a further two novel mutations in the gene. We discuss the distribution of mutations and the proportions of autosomal dominant AD with a mean age of onset below 60 years caused by mutations in this gene.

Alzheimer Disease↗
PubMed1996

Familial dementia with swollen achromatic neurons and corticobasal inclusion bodies: a clinical and pathological study.

Clinical, pathological and molecular genetic data are presented in two families in which 15 individuals have developed a progressive dementia. Clinical details are available in 10 individuals, neuropathological data in 2. Affected individuals presented between the ages of 43 and 59 years with personality change or memory loss. All individuals developed a progressive dementia with features of frontal lobe dysfunction. Affected individuals commonly developed additional features which included dysphasia, parkinsonism, limb clumsiness and disequilibrium. Duration to death was between 3 and 13 years. Pathological examination of one individual from each family revealed a combination of features not previously described in a familial dementia. Macroscopic examination revealed lobar atrophy. Microscopy revealed neuronal loss and gliosis with swollen achromatic neurons in the cortex and corticobasal inclusion bodies in the substantia nigra. On clinical assessment these families have many features of Pick's disease but pathological examination reveals features more suggestive of corticobasal degeneration.

Adult↗
PubMed1996

Characterization of human immunodeficiency virus type 1 p17 matrix protein motifs associated with mother-to-child transmission.

In order to determine if viral selection occurs during mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1), we used a direct solid-phase sequencing method to sequence the p17 matrix protein-encoding regions of viral isolates from 12 HIV-1-infected mother-and-child pairs, 4 infected infants, 4 transmitting mothers, and 22 nontransmitting mothers and compared the sequences. The blood samples were collected during the delivery period for the mothers and during the first month of life for most of the children. The p17 nucleic sequences were distributed among several clades corresponding to the HIV-1 A, B, and G subtypes. At the amino acid level, no significant differences within the known p17 functional regions were observed among the subtypes. Statistical analyses could be performed with the B subtype. Within the major p17 antibody binding site, a constant KIEEEQN motif (amino acids 103 to 109) was found in all mother-and-child isolates from the B subtype. On the other hand, 9 of 17 nontransmitting mother isolates were variable in this 103 to 109 region. Thus, this motif was significantly associated with the transmitting status (chi square, P = 0.0034). A valine residue at position 104 was significantly associated with the nontransmitting phenotype (chi square, P = 0.014), suggesting that it has a protective role during vertical transmission. The C-terminal end of p17 was globally conserved among nontransmitting mother isolates (chi square, P = 0.0037). These results might improve the understanding of the pathogenesis of HIV-1 vertical transmission and might allow the screening of seropositive mothers by a rapid molecular or peptide test.

Amino Acid Sequence↗
PubMed1995

Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer's Disease but is not causative.

An association has been observed in several independent data sets between late onset Alzheimer's Disease (AD) and the APOE locus on chromosome 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at-risk siblings of the FHP group we found an excess of the epsilon 4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and non-stringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease free survival suggested that APOE genotype contributes a small fraction of the total variance indicating that the APOE locus is a poor predictor of disease free survival age within late onset families. One explanation for the age dependent association reported by other groups, and our results, is that the APOE locus enhances the rate of progression of the disease process in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause the disease. We suggest this hypothesis is compatible with the current literature regarding APOE and AD.

Age Factors↗
PubMed1995

Deficits in cerebral glucose metabolism demonstrated by positron emission tomography in individuals at risk of familial Alzheimer's disease.

In order to establish whether positron emission tomography (PET) can identify metabolic changes in Alzheimer's disease at a presymptomatic stage, we have examined 24 asymptomatic at risk individuals from families with Alzheimer's disease. A significant reduction in global cerebral metabolic rate for glucose was found when compared with 16 age-matched controls. There was also a focal, parieto-temporal deficit similar to, although less extensive than, that found in 18 symptomatic individuals from familial Alzheimer's disease (FAD) pedigrees. Follow up of this cohort will establish whether these metabolic changes relate to a presymptomatic stage of the disease.

Adult↗
PubMed1995

Chromosome 14 linked familial Alzheimer's disease. A clinico-pathological study of a single pedigree.

The clinical features of three affected members of a British pedigree with familial Alzheimer's disease are presented. This pedigree is one of six included in an earlier study which demonstrated linkage to chromosome 14. The individuals were investigated clinically and neuropsychologically, using both PET and MRI over a 4-year period. Further information from three deceased individuals was obtained, including histopathological confirmation of Alzheimer's disease in one case which came to autopsy. The mean age at onset for this family was 43 years. Neurological examination revealed myoclonic jerks in all cases, and one patient was documented to have seizures. Strikingly similar neuropsychological profiles were observed, characterized by an initial memory deficit with early dyscalculia and an impairment in speech production with relative absence of anomia. All individuals showed mild degrees of cerebral atrophy and two individuals had periventricular white matter lesions. PET scanning using [18F]fluorodeoxyglucose showed parieto-temporal hypometabolism in all cases and the two severely affected patients with speech production changes had additional left-sided frontal hypometabolism involving Broca's area. The least affected case initially had a more asymmetrical reduction in metabolism in the left inferior temporal and supramarginal gyri; a follow-up scan showed that this deficit had become bilateral and more severe. These clinical and neuroimaging features have not been previously reported in chromosome 14 linked pedigrees; the phenotypic variability between families suggests allelic heterogeneity at the chromosome 14 locus.

Adult↗
PubMed1995

The sensitivity of HIV-1 DNA polymerase chain reaction in the neonatal period and the relative contributions of intra-uterine and intra-partum transmission.

OBJECTIVE: To derive reliable estimates of the sensitivity of HIV-1 DNA polymerase chain reaction (PCR) in the neonatal period and to quantify the relative contributions of intra-uterine and intra-partum transmission. METHODS: After reviewing studies on the early diagnosis of HIV-1 infection, investigators were asked to provide published and unpublished PCR test results on prospectively followed, non-breastfed, vertically infected children. Age-specific estimates of the sensitivity of PCR were derived using distribution-free methods for interval-censored data. RESULTS: Data on 271 infected children were combined for analysis. PCR detected HIV-1 DNA in an estimated 38% [90% confidence interval (CI), 29-46] of HIV-infected children tested on the day of, or day after, birth. Sensitivity was observed to rise rapidly in the second week of life, reaching 93% (90% CI, 76-97) by 14 days of age. CONCLUSION: The sensitivity of PCR in the neonatal period is higher than previously reported. This affects the clinical interpretation of an early negative test result and encourages the use of PCR as an endpoint for trials to evaluate interventions to reduce vertical transmission in non-breastfed populations. Approximately one-third of vertically acquired HIV-1 infection could be attributable to intra-uterine transmission.

DNA, Viral↗
PubMed1994

Confirmation that familial clustering and age of onset in late onset Alzheimer's disease are determined at the apolipoprotein E locus.

We confirm that familial clustering in late onset Alzheimer's disease is associated with the zeta 4 allele of apolipoprotein E. This allele occurs in the great majority (82%) of late onset familial Alzheimer cases. Together with previously published data, it is suggested that the effect of a single zeta 4 allele is to increase the risk of developing AD by an amount equivalent to 5 years and that the effect of zeta 4 homozygosity is to increase the risk of developing AD by an amount equivalent to 10 years of age.

Age of Onset↗