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Biomedical subjects

P Roques

Publications and source records attributed to P Roques.

At least 19 recordsLinked to original sources
PubMed1992

Specific and non-specific immunity and protection of macaques against SIV infection.

The simian immunodeficiency virus is a retrovirus closely related to the human immunodeficiency viruses; it induces an AIDS-like disease in macaques, and provides therefore an obvious animal model for anti-lentiviral drug and vaccine strategy assessments. In our experiment, we immunized rhesus macaques with a purified and formalin-inactivated whole SIVmac251 antigen preparation. Most of these monkeys were still protected for more than 4 months following a heterologous SIVsm intravenous challenge. Both virus stocks, for vaccine preparation and challenge, were provided by culture supernatants of infected T cells of human origin. Four of the protected macaques were then reimmunized with the same antigen preparation and rechallenged intravenously with a homologous rhesus cell grown SIVmac251. Unexpectedly, all animals developed clinical and biological evidence of infection by day 15 after the second challenge.

Animals↗
PubMed1992

Screening for mutations in the open reading frame and promoter of the beta-amyloid precursor protein gene in familial Alzheimer's disease: identification of a further family with APP717 Val-->Ile.

Following the identification of mutations in the beta-amyloid precursor protein (APP) gene in familial, early onset Alzheimer's disease (AD), we have developed a screening protocol using single strand conformation analysis (SSCA) to screen exon 17 for the known mutations within APP. In addition, we used this protocol to screen the other seventeen exons of APP and a three hundred and thirty base pair regulatory region of the promoter for new mutations in 9 families with early onset AD. Exons 16 and 17, which encode the deposited beta-amyloid peptide, were screened in a further 10 families. Our screening procedure identifies all the reported mutations within APP. While we have identified a further family with APP717 Val-->Ile, we did not find any previously undescribed mutations. Screening of other exons of APP in 2 families in which we have previously reported mutations at APP717, failed to reveal other sequence abnormalities supporting the hypothesis that the mutations at APP717 cause the disease in these families. These data suggest that mutations in APP are a rare cause of familial early onset AD (3/21 families tested) and that within APP most, possibly all, mutations which cause AD are in exon 17.

Adult↗
PubMed1991

Sequencing of exons 16 and 17 of the beta-amyloid precursor protein gene in 14 families with early onset Alzheimer's disease fails to reveal mutations in the beta-amyloid sequence.

A mutation within exon 17 at codon 717 of the beta-amyloid protein precursor (APP) gene is one cause of early onset familial Alzheimer's disease. Direct sequencing of exons 16 and 17 of the beta-amyloid precursor protein gene in 14 families with familial early onset Alzheimer's disease without the known pathogenic mutation (APP717) failed to reveal other mutations within the beta-amyloid sequence in this form of the disorder.

Adult↗
PubMed1991

Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene.

A mutation at codon 717 of the beta-amyloid precursor protein gene has been found to cosegregate with familial Alzheimer's disease in a single family. This mutation has been reported in a further five out of approximately 100 families multiply affected by Alzheimer's disease. We have identified another family, F19, in which we have detected linkage between the beta-amyloid precursor protein gene and Alzheimer's disease. Direct sequencing of exon 17 in affected individuals from this family has revealed a base change producing a Val----Gly substitution, also at codon 717. The occurrence of a second allelic variant at codon 717 linked to the Alzheimer's phenotype supports the hypothesis that they are pathogenic mutations.

Alzheimer Disease↗
PubMed1989

A new type of chemically modified tRNA as a tool for the study of tRNA-aminoacyl-tRNA synthetase interaction.

tRNA(Phe) in which the adenine and cytosine rings in the aminoacyl arm and in the anticodon loop were converted to alkylating derivatives by mild treatment with methyl chlorotetrolate was used to study the tRNA(Phe)-yeast phenylalanyl-tRNA(Phe) synthetase interaction. At neutral pH, modified tRNA inhibited the enzyme competitively. At pH 9 this binding is accompanied by irreversible inactivation of the enzyme due to alkylation of the alpha subunit of the synthetase. Such a derivatization of tRNA could probably be used to investigate the interaction of other tRNAs with their cognate synthetases.

Alkylation↗
PubMed1989

Predisposing locus for Alzheimer's disease on chromosome 21.

Linkage between Alzheimer's disease and markers on the long arm of chromosome 21 was investigated in six families affected by disease of early onset. Linkage was confirmed and the disease locus shown to be centromeric to the locus D21S1/S11 on the long arm of the chromosome. It is argued that the data are consistent with the notion that all patients with Alzheimer's disease of genetic aetiology have a predisposing locus on chromosome 21.

Adult↗
PubMed1988

Reaction of nucleic acid bases with alpha-acetylenic esters. Part IV. Preparation of an alkylating derivative of tRNA(Phe) by conformation-specific chemical modification.

The reaction of yeast tRNA(Phe) with methyl chlorotetrolate, ClCH2-C identical to C-COOCH3, was studied. This reagent converts adenine and cytosine rings into derivatives in which an additional heterocycle bearing the alkylating chloromethyl group is fused to the original base; these derivatives can exist in two isomeric forms. Modified nucleosides of this type can be easily identified by reverse-phase HPLC. It was found that under native conditions, the modification of tRNA involves the anticodon loop and the 3'-end. The isomers of adenine derivatives formed in the anticodon loop were different from those formed in the 3'-end. It is suggested that the isomeric structure of the derivatives is related to the fine conformational differences between these two regions of tRNA(Phe). Methyl chlorotetrolate could thus be used as a conformational probe of single-stranded nucleic acids. Preliminary assays showed that modified tRNA(Phe) binds irreversibly to yeast phenylalanyl-tRNA synthetase.

Alkylation↗
PubMed1988

Platelet serotonin content and plasma tryptophan in peri- and postmenopausal women: variations with plasma oestrogen levels and depressive symptoms.

Platelet serotonin content was measured by high pressure liquid chromatography in 56 peri- and postmenopausal women, in order to study variations of this parameter with hormonal status and depressive mood symptoms. Clinical symptoms were assessed by a self-report depression symptom scale (CES-D of NIMH). Thirty-eight women with a score of 16 or more were considered as presenting depressive symptoms (mean score +/- SD = 28.8 +/- 10.5), while the others formed the control group (n = 18, score = 4.4 +/- 4.2). Platelet serotonin contents were significantly lower in the 'depressed' group (0.302 +/- 0.010 vs. 0.366 +/- 0.020 nmol 10(-8) platelets, means + SEM, P less than 0.001 by Mann-Whitney U-test). In 'depressed' women who had been treated for one or more depressive episodes, platelet 5-HT contents (0.283 +/- 0.023, n = 18, P less than 0.01) were significantly lower with respect to controls. In patients without previous episodes of depression, serotonin expressed in nmol 10(-8) platelets did not differ significantly from controls but serotonin expressed in nmol ml-1 of blood was slightly lower than control values (0.890 +/- 0.085, n = 20 vs. 1.088 +/- 0.090 nmol ml-1, n = 18, P less than 0.02). Platelet serotonin content was positively correlated to plasma oestrone and oestradiol concentrations among the control group but not in the 'depressed' group.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1987

Reactions of nucleic acid bases with alpha-acetylenic esters. Chemical modification of poly(A) and poly(C).

The reaction of chlorotetrolic (4-chloro-2-butynoic) esters with adenine and cytosine derivatives, in which a new heterocycle bearing an alkylating chloromethyl side chain is fused to the purine or pyrimidine ring, was extended to poly(A) and poly(C) used as models of nucleic acids. The derivatization proceeds under mild conditions and its extent can be controlled by the reaction time. The additional rings can exist in two isomeric forms and the nature of the isomer formed depends on steric factors in the vicinity of the reacting base. The reaction with chlorotetrolic esters discriminates between the single-stranded (reactive) and double-stranded (unreactive) forms, between the exposed an hidden adenine and cytosine bases and even between the exposed and sterically hindered fragments of the base moiety and thus allows structural investigations of these nucleic acids. The chloromethyl group of the derivatized nucleobases can be used to bind the modified polymers to other molecules.

Alkaline Phosphatase↗
PubMed1985

Platelet serotonin and blood tryptophan in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

The number of platelets and their content in serotonin (5-HT) were determined in 12-week-old spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) and in normotensive Wistar-Kyoto rats (WKY). Spontaneously hypertensive rats had 49% more platelets and a 65% higher platelet 5-HT circulating pool than SHRSP and WKY. An increased synthesis of 5-HT by enterochromaffin cells in SHR is suggested by the lower level of plasma total and albumin-bound tryptophan and by the higher free/bound tryptophan ratio found in those rats, as compared with WKY. In SHRSP, a decrease of platelet survival time was reported, associated to an increased platelet production. This would explain the absence of variation of platelet number and 5-HT content.

Animals↗