Biomedical subjects

Y Perrin

Publications and source records attributed to Y Perrin.

8 recordsLinked to original sources

PubMed2004

[Drug interaction computer programs: which choice?].

Adverse drug reactions represent a partly preventable cause of morbidity. Computer-based tools may be useful for the prevention of those events resulting from drug interactions. While several such tools are currently available to practitioners, they have rarely been compared regarding their performances and limits. This article presents a benchmark evaluation of seven drug interaction databases which may be elected by physicians or pharmacists as an aid to prescription on a regular basis. None of the databases tested appears to be perfect, and the systems vary in their overall completeness and ease of use.

Adverse Drug Reaction Reporting Systems↗

PubMed2001

Native and artificial reticuloplasmins co-accumulate in distinct domains of the endoplasmic reticulum and in post-endoplasmic reticulum compartments.

We compared the subcellular distribution of native and artificial reticuloplasmins in endosperm, callus, and leaf tissues of transgenic rice (Oryza sativa) to determine the distribution of these proteins among endoplasmic reticulum (ER) and post-ER compartments. The native reticuloplasmin was calreticulin. The artificial reticuloplasmin was a recombinant single-chain antibody (scFv), expressed with an N-terminal signal peptide and the C-terminal KDEL sequence for retrieval to the ER (scFvT84.66-KDEL). We found that both molecules were distributed in the same manner. In endosperm, each accumulated in ER-derived prolamine protein bodies, but also in glutelin protein storage vacuoles, even though glutelins are known to pass through the Golgi apparatus en route to these organelles. This finding may suggest that similar mechanisms are involved in the sorting of reticuloplasmins and rice seed storage proteins. However, the presence of reticuloplasmins in protein storage vacuoles could also be due to simple dispersal into these compartments during protein storage vacuole biogenesis, before glutelin deposition. In callus and leaf mesophyll cells, both reticuloplasmins accumulated in ribosome-coated vesicles probably derived directly from the rough ER.

Calcium-Binding Proteins↗

PubMed2000

Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies.

This report describes the stable expression of a medically important antibody in the staple cereal crops rice and wheat. We successfully expressed a single-chain Fv antibody (ScFvT84.66) against carcinoembryonic antigen (CEA), a well characterized tumor-associated marker antigen. scFv constructs were engineered for recombinant antibody targeting to the plant cell apoplast and ER. Up to 30 microg/g of functional recombinant antibody was detected in the leaves and seeds of wheat and rice. We confirmed that transgenic dry seeds could be stored for at least five months at room temperature, without significant loss of the amount or activity of scFvT84.66. Our results represent the first transition from model plant expression systems, such as tobacco and Arabidopsis, to widely cultivated cereal crops, such as rice and wheat, for expression of an antibody molecule that has already shown efficacy in clinical applications. Thus, we have established that molecular pharming in cereals can be a viable production system for such high-value pharmaceutical macromolecules. Our findings provide a strong foundation for exploiting alternative uses of cereal crops both in industrialized and developing countries.

Animals↗

PubMed1999

Original reverse transcription polymerase chain reaction method to obtain the full-length cDNA of rice tungro spherical virus.

A two-step reverse transcription reaction combined with long PCR was developed in order to obtain the full-length cDNA from the 12.2 kbp genomic RNA of rice tungro spherical virus. A first step reverse transcription, performed at 45 degrees C using a reverse transcriptase deprived of RNase H activity, allowed the synthesis of a nearly full-length cDNA of 11.7 kbp. A second step reaction, carried out at 65 degrees C using a thermostable polymerase, was necessary to destabilise secondary structures present at the 5' extremity of the RNA template which hampered the reverse transcription reaction in this region. The full-length cDNA obtained by the two-step reverse transcription was amplified successfully by long PCR and subsequently cloned into a plasmid vector. The cloned cDNA showed toxicity and proved to be unstable when amplified in E. coli.

Cloning, Molecular↗

PubMed1999

Rice cell culture as an alternative production system for functional diagnostic and therapeutic antibodies.

We investigated the suitability of transformed rice cell lines as a system for the production of therapeutic recombinant antibodies. Expression constructs encoding a single-chain Fv fragment (scFvT84.66, specific for CEA, the carcinoembryonic antigen present on many human tumours) were introduced into rice tissue by particle bombardment. We compared antibody production levels when antibodies were either secreted to the apoplast or retained in the endoplasmic reticulum (ER) using a KDEL retention signal. Production levels were up to 14 times higher when antibodies were retained in the ER. Additionally, we compared construct sencoding different leader peptides (plant codon optimised murine immunoglobulin heavy and light chain leader peptides from mAb24) and carrying alternative 5' untranslated regions (the petunia chalcone synthase gene 5' UTR and the tobacco mosaic virus omega sequence). We observed no significant differences in antibody production levels among cell lines transformed with these constructs. The highest level of antibody production we measured was 3.8 micrograms g-1 callus (fresh weight). Immunological analysis of transgenic rice callus confirmed the presence of functional scFvT84.66. We discuss the potential merits of cell culture for the production of recombinant antibodies and other valuable macromolecules.

5' Untranslated Regions↗

PubMed1980

Nuclear scattering radiography.

The quasi-elastic scattering of 1 GeV protons permits the three-dimensional reconstruction of the density distribution in extended bodies. Fast multiwire proportional chambers are used to localize the position of every incoming and outgoing charged particle and to determine the coordinates at the interaction vertex. This article describes tests on a human head fixed on formalin. The comparison with computed tomography scans and anatomical sections is encouraging. Slices with a volume element of 5.5 mm3 illustrate the sensitivity of the method. The results also demonstrate the ability of the method to select the density distribution of hydrogen by making use of the kinematic relations specific to elastic scattering. Trials of this method in living humans are being planned.

Brain↗

PubMed1976

Further results in nuclear scattering radiography.

A further investigation of the nuclear scattering of 500-1000 MeV protons is described. Three-demensional information on the desity distribution within carbon, CH and H2O phantoms is obtained with a volume resolution of 2 mm3. The separation of scattering on hydrogen from that on heavier nuclei, such as carbon and oxygen, is demonstrated, providing the statistics are sufficient. Some preliminary measurements on animals are reported, but with a volume resolution limited by statistics to 43 mm3.

Animals↗

PubMed1975

[Epidemic of autochthonous hepatic and intestinal amebiasis in a place near Grenoble].

We had the opportunity of studying an epidemic of autochthonous amoebiasis occurring in the autumn of 1974 in a small town of 4000 inhabitants 30 km from Grenoble. Attention was originally attracted by the occurrence in this town of two cases of hepatic amoebiasis and one of intestinal amoebiasis identified by rectoscopy. Systematic investigations (coproctic examinations and serological tests for amoebiasis by indirect antibody fluorescence) were then carried out on everyone in the locality with digestive disorders which were possibly referable to amoebiasis, and on the other members of their families. A total number of 148 coproctic examinations were made and in two cases revealed the presence of vegetative forms of Entamoeba histolytica. In both cases the infestation provoked few symptoms (asthenia, vague abdominal discomfort, intermittent and apparently banal diarrhoea). On the other hand 20 out of 94 serological tests revealed positive results, 14 of which were equal to or greater than a titre of 1/100, a level at which all risks of non-specificity are virtually ruled out under our experimental conditions. Material reasons made it impossible to subject these cases to repeated faecal checks, but in two of them at least the rectoscopic appearances were very suggestive of subacute intestinal amoebiasis. Moreover, amoebic disease appears to be well confirmed by the results obtained among the patients as a whole by treatment with Metroinidazole. A variety of hypotheses on the origin of this epidemic have been put forward and then abandoned (market garden produce, receipt by certain families of exotic frut from overseas). In actual fact water seems to be the point of departure, for, although specimens of water taken at 7 different levels in the water supply system failed to reveal the presence of a single amoeba, bacteriological analyses during autumn 1974 showed signs of faecal contamination. The locality, which is situated at the foot of the Chartreuse massif, receives its water solely from springs but there is a holiday camp for the staff of an international airline situated above the main water catchment.

Dysentery, Amebic↗