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Biomedical subjects

J M Gabriel

Publications and source records attributed to J M Gabriel.

30 records · Page 2Linked to original sources

Immunologic and molecular biologic studies of prion proteins in bovine spongiform encephalopathy.

Bovine spongiform encephalopathy (BSE) is a transmissible neurodegenerative disease. Six brain regions from 11 cattle were examined for the presence of the abnormal isoform of the prion protein (PrPBSE). The highest concentrations of PrPBSE were found in the brain stem, where the greatest degree of spongiform change was observed. Molecular cloning of the bovine PrP gene showed that it encodes a protein of 256 or 264 amino acids with five or six Gly:Pro-rich octarepeats, respectively, in contrast to all other mammalian PrP genes, which encode only five octarepeats. The bovine PrP gene is single copy, and the entire open-reading frame lies within a single exon. Since the transmission of prions across species seems to be restricted by differences in PrP sequence, the high degree of homology between sheep and bovine PrP (98%) correlates with the proposed cause of BSE.

Amino Acid Sequence↗

[Pathology of travelers in the Antilles. Role of imported metropolitan pathology].

A preliminary and retrospective review--with a southern perspective--of some traveller's pathologies, mostly imported, and leading to hospital admission in Guadeloupe (FWI). End stage patients (cancer, AIDS...) frequently travel for a last, "compassional" trip. Ischemic heart disease is the leading pathology imported from the mother country (France). As well as in diabetes or psychiatric illness, destabilization frequently occurs as a consequence of travel (jet lag). Compulsive tennis plus dehydration cause the very common stone passage of nephrolithiasis. Concern is growing for heroin withdrawal syndrome or cocaine (crack)-abuse, and for supply for rare and expensive anticancer, antigraft rejection or antinfective (AIDS) agents. Much more familiar to us are photodermatitis, larva migrans, dengue, or ciguaterra, locally acquired. On the other hand some pathologies are quite "exotic" to us: Kaposi sarcoma, Lyme, or Behçet disease, familial mediterranean fever, brucellosis.

Epidemiology↗

Predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloid.

By comparing the amino acid sequences of 11 mammalian and 1 avian prion proteins (PrP), structural analyses predicted four alpha-helical regions. Peptides corresponding to these regions of Syrian hamster PrP were synthesized, and, contrary to predictions, three of the four spontaneously formed amyloids as shown by electron microscopy and Congo red staining. By IR spectroscopy, these amyloid peptides exhibited secondary structures composed largely of beta-sheets. The first of the predicted helices is the 14-amino acid peptide corresponding to residues 109-122; this peptide and the overlapping 15-residue sequence 113-127 both form amyloid. The most highly amyloidogenic peptide is AGAAAAGA, which corresponds to Syrian hamster PrP residues 113-120 and is conserved across all species for which the PrP sequence has been determined. Two other predicted alpha-helices corresponding to residues 178-191 and 202-218 form amyloids and exhibit considerable beta-sheet structure when synthesized as peptides. These findings suggest the possibility that the conversion of the cellular isoform of PrP to the scrapie isoform of PrP involves the transition of one or more putative PrP alpha-helices into beta-sheets and that prion diseases are disorders of protein conformation.

Amino Acid Sequence↗

Molecular cloning of a candidate chicken prion protein.

Fractions enriched for acetylcholine receptor-inducing activity from chicken brain were found to contain a protein that was approximately 30% homologous with mammalian prion proteins [Harris, D. A., Falls, D. L., Johnson, F. A. & Fischbach, G. D. (1991) Proc. Natl. Acad. Sci. USA 88, 7664-7668]. To extend these observations, we recovered genomic clones encoding a putative chicken prion protein (PrP). Like mammalian PrP molecules, the candidate chicken PrP is encoded by a single-copy gene and the entire open reading frame is found within a single exon. All of the structural features of mammalian PrP were found in the chicken protein. When the N-terminal repeats of PrP were not considered, the chicken and mammalian proteins were approximately 55% homologous, allowing for conservative substitutions. Screening of a chicken genomic DNA library failed to identify a more closely related chicken PrP homologue. These findings argue that the protein which purifies with acetylcholine receptor-inducing activity is chicken PrP.

Amino Acid Sequence↗

Alcohol consumption in Guadeloupe.

This study bears upon the patterns of alcohol consumption in Guadeloupe (French West Indies), and has been carried out over a representative sample of adults. Each subject was questioned about his or her consumption of alcoholic drinks and a blood sample taken to measure the biological indicators of chronic alcohol consumption. The resulting mean consumption has permitted Guadeloupeans to be classed among the world's foremost consumers of alcohol. For almost half of the adult population, this consumption takes place on a daily basis and therefore constitutes part of everyday life. The patterns of alcohol consumption are linked to sex, age, level of education, employment and socio-professional categories. The heavy-drinking man tends to be elderly, has a low level of education and is an agricultural worker; his consumption is based on rum. The woman is middle-aged and not working; her consumption is based on wine. These stated characteristics permit the setting up of tailored prevention programs.

Accidents, Traffic↗

Monoclonal antibodies to the main immunogenic region of the nicotinic acetylcholine receptor bind to residues 61-76 of the alpha subunit.

Monoclonal antibodies (mAbs) to the main immunogenic region (MIR) bind to fusion proteins containing region 37-200 of the alpha chain of Torpedo, mouse, and chicken nicotinic acetylcholine receptor. In the case of the mouse alpha chain, these mAbs react with sequence 61-216 but not with 74-216. A synthetic peptide M1, containing residues 61-76 of the mouse alpha chain, also binds these anti-MIR mAbs, showing that all or part of their binding site is included in this region. The conformational dependence and epitope specificity of the mAbs are discussed.

Amino Acid Sequence↗

[AIDS and HIV infection in Guadeloupe].

By December 31, 1986, 38 cases of AIDS had been notified in Guadeloupe (French West Indies). Transmission of the disease was predominantly heterosexual; 79 p. 100 of the patients were devoid of risk factor. Sex ratio was 2.2, but the disease, which initially was mostly observed in men, seems to be developing rapidly in women. Fearing an increase in infantile mortality due to AIDS, the authors recommend routine screening of pregnant women for anti-HIV antibody.

Acquired Immunodeficiency Syndrome↗

Study of HLA antigens in systemic lupus erythematosus in the French West Indies.

As incidence of SLE is high in Blacks, we studied HLA and SLE associations in the French West Indies, whose population is racially mixed. Forty-seven coloured SLE patients have been typed in HLA A,B,C and DR. We observed B8 association in nearly all of the studies. B15 association, more frequent in Caucasians, was found, also B53 association, a Black variant of B5 more frequent in Blacks. We did not find any class II association.

HLA Antigens↗

Localisation of the main immunogenic region of the nicotinic acetylcholine receptor.

The nicotinic acetylcholine receptor from Torpedo marmorata was digested using papain and the reaction products separated by SDS gel electrophoresis and characterised by immunoblotting using labelled alpha-bungarotoxin, polyclonal antibodies to synthetic peptides and monoclonal antibodies to the main immunogenic region (MIR). Using this approach, it was possible to show that the MIR is located N-terminal to all or part of peptide 151-169 (peptide P1) of the alpha-chain and that papain cleaves the alpha-chain between Asn 141 and peptide P1.

Animals↗