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Biomedical subjects

P Perrin

Publications and source records attributed to P Perrin.

At least 37 records · Page 2Linked to original sources

DNA-based immunization against Lyssaviruses.

Rabies is a fatal encephalomyelitis. Most cases occur in developing countries and are transmitted by dogs. Because of their high cost, cell culture vaccines have not totally replaced the unsafe brain-derived vaccines which are still used in many developing countries. Moreover, there will be a need for vaccines against rabies-related viruses against which classical vaccines are not always effective. DNA vaccines would, therefore, be a valuable alternative for the production of cheaper rabies vaccines against a larger spectrum of viruses. In this review we report published data on DNA-based immunization with sequences encoding rabies and rabies-related virus antigens.

Animals↗

[The operating microscope in dental general practice].

The great advantages of using a stereoscopic operating microscope in endodontics and especially in endodontic surgery are being increasingly advocated in postgraduate training courses and numerous publications. Widely underestimated, however, is the fact that this tool may open new horizons to almost all dental specialities and will improve ergonomics of the dental work place. Moreover, the superb images may contribute some pleasure to the daily dental work and stress. All this makes the clinical stereoscope interesting also for the general practice of dentistry. The purpose of this paper is to report about several years of practical experience with the "scope" in general dentistry. Technical aspects are discussed as well as the possibilities of use. Practical hints regarding the type of scope and the technique of its use are given in order to lower the barrier of entrance into this new era of doing dental work.

Dentistry, Operative↗

[Intravesical BCG-therapy: comparison of side effects of Connaught (Toronto) and Pasteur (Paris) strains].

INTRODUCTION: Urologists have felt that the adverse effects of intravesical BCG-therapy have been more serious and more frequent since the use of the Connaught strain. The objective of this retrospective study was to compare the toxicity of this new strain with that previously used in France (Pasteur strain). MATERIAL AND METHODS: After endoscopic resection, 89 patients with stage Ta grade 1-2 recurrent or T1 grade 3 and/or CIS bladder tumour were treated with 6 instillations of 150 mg of BCG Pasteur from 1992 to 1996 (50 patients: group 1) or 81 mg of BCG Connaught from January 1997 to December 1998 (39 patients: group 2). Adverse effects were classified as minor, lasting less than 48 hours (bladder irritation syndrome and/or macroscopic haematuria and/or fever less than 38 degrees C), moderate (requiring symptomatic treatment, reduction of the dose or an increased interval between instillations), and major (contraindication to continuation of treatment). RESULTS: 74% of patients in group 1 presented at least one adverse effect versus 77% in group 2. The reasons for permanent discontinuation of BCG-therapy in groups 1 and 2, respectively, were as follows: malaise during instillation (1 vs 0), bladder irritation syndrome not controlled by symptomatic treatment (4 vs 5) and epididymitis (0 vs 1). Pulmonary tuberculosis was diagnosed in one patient from group 2, one year after the last instillation. The frequency and severity of adverse effects were not statistically different between the two groups. The number of patients discontinuing BCG-therapy because of severe complications was also not statistically different between the two groups. CONCLUSION: This study did not reveal any difference of toxicity between Connaught and Pasteur strain in intravesical BCG-therapy of superficial bladder tumours.

Adjuvants, Immunologic↗

DNA-based immunisation against rabies and rabies-related viruses: towards multivalent vaccines.

Prototypes of multivalent DNA vaccines against lyssaviruses (LV: rabies and rabies-related viruses) and other viruses were developed using chimaeric LV glycoprotein (cLVG) DNA and cLVG DNA carrying foreign epitopes. cLVG is composed of the N-terminal half of an LV genotype (GT) containing antigenic site II, the C-terminal half of GT containing antigenic site III, as well as the transmembrane and cytoplasmic domains of the same or a different GT. Both antigenic sites induced virus neutralizing antibodies (VNAb). Foreign B and T cell epitopes inserted between the two halves of cLVG correspond to the B cell C3 neutralisation epitope of poliovirus VP1 protein and to the H2d CMH I restricted T cell epitope of the nucleoprotein of the lymphocytic choriomeningitis virus (LCMV). In mice and dogs homogenous rabies virus G DNA induced protection against wild-type rabies virus whereas cLVG protected against lyssaviruses. cLVG DNA carrying foreign epitopes induced VNAb against LV and poliovirus and protection against LCMV. The results obtained clearly demonstrate the potential usefulness of cLVG for the development of multivalent vaccines against viral diseases, including rabies and zoonoses.

Animals↗

Immunization of dogs with a DNA vaccine induces protection against rabies virus.

Rabies is a fatal encephalomyelitis which is transmitted to man, mostly by dogs in developing countries. This zoonosis can be prevented by vaccination of humans before or after exposure. However, a more radical approach is possible, involving the elimination of the principal vector/reservoir by vaccinating dogs. The vaccine must be effective, safe and inexpensive. Mass production of plasmids is possible and DNA-based immunization with a plasmid encoding the antigen responsible for inducing protection seems to be more cost-effective than classical techniques involving cell culture. Beagles were immunized by intramuscular (i.m.) injection with a plasmid encoding the rabies virus (PV strain) glycoprotein. Neutralizing antibodies against both wild-type rabies virus and European Bat Lyssaviruses (EBL1 and EBL2) were detected after a single injection and a boost, but levels of neutralizing antibodies against EBL1 were low. Moreover, all vaccinated dogs were protected against a lethal challenge with a wild-type dog rabies strain. This is one of the first studies to demonstrate that dogs can be protected by DNA vaccines, and opens important perspectives for rabies control.

Animals↗

[Influence of aluminum adjuvant to experimental rabies vaccine].

OBJECTIVE: To study whether the rabies vaccine for human use should contain aluminum adjuvant. METHODS: Testing vaccine antibodies and efficacy (ED50), comparing the effect between aluminum adjuvant contained and non-aluminum adjuvant contained vaccines in a new animal model which accords with the rabies field practice. RESULTS: At fourth and seventh day after immunization, the neutralizing antibody titres of the rabies vaccine containing aluminium adjuvant were much lower than that of the vaccine not containing aluminum adjuvant. In the NIH efficacy test the ED50 of the vaccine containing aluminum adjuvant was 93-132 ng while the ED50 of the vaccine not containing aluminum adjuvant was 221 ng, but the NIH test does not accord with the rabies field practice. In that new animal model, aluminum adjuvant to rabies vaccine had not any promoting effect for preventing and treating rabies. CONCLUSION: Aluminum adjuvant to rabies vaccine has no advantages, this paper suggests that the vaccines containing and not-containing aluminium adjuvant had better compare in human bodies. If the results are the same as our experiments, the aluminum adjuvant should be eliminated from rabies vaccine for human use.

Adjuvants, Pharmaceutic↗

Is there an advantage to including the nucleoprotein in a rabies glycoprotein subunit vaccine?

The PV rabies (genotype 1) G and N proteins were produced by recombinant baculoviruses in insect cells. We tested the ability of recombinant antigens to synergistically induce an immune response and, particularly, to broaden the spectrum of Lyssavirus-neutralizing antibodies produced. Cell-free preparations of recombinant proteins caused an immune response. Recombinant rabies G protein (RRG) from infected cell extract or supernatant induced virus neutralizing antibodies (VNAb) against rabies (CVS virus (genotype 1) and in a less extent against European Bat Lyssavirus-1 (EBL-1:genotype 5) Recombinant rabies N protein (RRN) induced antibodies that reacted with the rabies virus ribonucleoprotein (RNP) and primed mice for both the production of VNAb induced by inactivated and purified rabies virus and the protection conferred by RNP. RRN also had an adjuvant effect on VNAb production induced by RRG when the two recombinant proteins were physically associated either encapsulated in liposomes or subjected to ultrasound treatment. However, there was no increase in production of VNAb directed against EBL-1 although classical vaccines (genotype 1) induce partial protection against this virus. thus, beside its adjuvant effect there is some doubt as to whether including rabies N protein in a rabies subunit vaccine containing the recombinant G protein would be advantageous.

Animals↗

Postural control of ballet dancers: a specific use of visual input for artistic purposes.

Dance is a specific expression of human motor behaviour. This artistic physical activity depends upon an effective technical training with important postural components and necessitates the codification of sensory inputs to build mental representations of the action to be produced. Proprioception and vision being two fundamental sensory modalities in classical ballet, this study attempted to determine the importance of the visual input for postural control during the practice of this activity. First, this work compared the performances of 18 professional ballet dancers and 46 non-dancers on a platform of forces during static posturographic tests in open or closed eyes situation. Then, we studied how professional dancers achieve balance in postures specific of classical ballet: on demi-pointe and on pointe. The results indicate that visual inputs are important in classical ballet since dancers only performed better than controls in eyes open conditions. The similar results obtained on pointe with eyes open or closed conversely suggest that training in classical ballet develops specific modalities of balance which are not transferable to posture control in daily life situations.

Adolescent↗

T cell status influences colon tumor occurrence in min mice fed short chain fructo-oligosaccharides as a diet supplement.

We have previously shown that addition of short chain fructo-oligosaccharides (indigestible carbohydrates) to food prevented colon tumors in C57BL/6-Apc(Min/+) mice, a model for human colon cancer. As gut-associated lymphoid tissue was concomitantly developed, we suggested that the immune response generated by this food may interfere with carcinogenesis due to involvement of mucosal cells in the regulation of tissue homeostasis. In the present experiment, we tested whether T cell status may influence colon tumor formation in Min mice fed a food supplement of short chain fructo-oligosaccharides. Min mice depleted of CD4(+) and CD8(+) lymphocytes developed twice as many tumors as immunocompetent mice (0.8 as compared with 0.4, the mean number in 7-week-old Min mice when food supplementation began; P = 0.02). It is concluded that food supplementation with a substrate (a known prebiotic) fermented in the colon may stimulate a mechanism of immunosurveillance that would otherwise remain inefficient.

Animals↗

Vertical free-standing films of amphiphilic associating polyelectrolytes.

Hydrophobically modified poly(acrylic acid) sodium salt (HMPAANa) copolymers are known to provide a huge stabilization of oil in water macroemulsions. An interstitial HMPAANa film is formed between the oil droplets, thus creating repulsion between them. We present an x-ray reflectivity study of vertical free-standing films drawn from aqueous solutions of HMPAANa copolymers. The vertical HMPAANa films are model systems for the interstitial films between oil droplets and the description of their behavior provides information about the stabilization process. Their thickness was investigated as a function of various parameters such as the solution concentration, the degree of grafting, the length of the grafts, and the backbone molecular weight. Below a solution concentration threshold (C(t)), the film thickness scales like the square root of the molecular weight and is independent of the degree of grafting and the length of the grafts. Polyelectrolyte chains adopt a self-screened coil conformation within the films and the thickness is governed by the radius of gyration of the coils. Above C(t), a transition from a bimolecular film to a physical gel is observed and the thickness then increases with concentration. Finally, we propose an explanation for the stabilization of macroemulsions by HMPAANa copolymers.

Journal Article↗

Chimeric lyssavirus glycoproteins with increased immunological potential.

The rabies virus glycoprotein molecule (G) can be divided into two parts separated by a flexible hinge: the NH2 half (site II part) containing antigenic site II up to the linear region (amino acids [aa] 253 to 275 encompassing epitope VI [aa 264]) and the COOH half (site III part) containing antigenic site III and the transmembrane and cytoplasmic domains. The structural and immunological roles of each part were investigated by cell transfection and mouse DNA-based immunization with homogeneous and chimeric G genes formed by fusion of the site II part of one genotype (GT) with the site III part of the same or another GT. Various site II-site III combinations between G genes of PV (Pasteur virus strain) rabies (GT1), Mokola (GT3), and EBL1 (European bat lyssavirus 1 [GT5]) viruses were tested. Plasmids pGPV-PV, pGMok-Mok, pGMok-PV, and pGEBL1-PV induced transient expression of correctly transported and folded antigens in neuroblastoma cells and virus-neutralizing antibodies against parental viruses in mice, whereas, pG-PVIII (site III part only) and pGPV-Mok did not. The site III part of PV (GT1) was a strong inducer of T helper cells and was very effective at presenting the site II part of various GTs. Both parts are required for correct folding and transport of chimeric G proteins which have a strong potential value for immunological studies and development of multivalent vaccines. Chimeric plasmid pGEBL1-PV broadens the spectrum of protection against European lyssavirus genotypes (GT1, GT5, and GT6).

Amino Acid Sequence↗

Observation/delayed treatment for rising PSA after radical prostatectomy: pros and cons.

The protracted natural history of prostate cancer and the absence of a documented effective seconde line curative therapy, once primary treatment has failed, has led in the presence of biochemical failure after radical prostatectomy to a dual attitude: early treatment versus observation with delayed therapy. The objective of this review is to define the subsets of patients who might benefit from either of these attitudes. Depending on the risk of progression, three subgroups of patients may be individualized: a high-risk group (PN1, pT3 B, Gleason score equal or superior to 8), a moderate-risk group (pT3 A, NO with positive margins, and a Gleason score equal or less than 7), and a low-risk group (pT2 NO or pT3 A NO without positive margins and Gleason score equal or lower than 7). As of today, observation seems to be the appropriate option in men with a low or moderate risk of progression, whereas in the high-risk group, early therapy is a reasonable option. New treatment options with intermittent hormonal therapy or with combined adjuvant hormonoradiotherapy show a promising efficacy that may lead to reconsider this attitude.

Humans↗

Review of recent placebo-controlled trials utilizing phytotherapeutic agents for treatment of BPH.

BACKGROUND: In order to assess the efficacy of phytotherapeutic agents for the treatment of benign prostatic hyperplasia (BPH), a review of recently published double-blind placebo-controlled trials was undertaken. METHODS: Only those studies reviewed by the Other Medical Therapies Committee of the Fourth International Consultation on BPH were included. RESULTS: These studies suggest a possible benefit for the use of phytotherapeutic preparations in the treatment of BPH. CONCLUSIONS: These studies need to be confirmed in larger long-term placebo-controlled studies in order to ascertain the true efficacy of these agents.

Anti-Bacterial Agents↗

Diversity of sequence haplotypes associated with beta-thalassaemia mutations in Algeria: implications for their origin.

We report the allelic sequence polymorphism associated with seven beta-thalassaemia mutations. Thirty-two DNAs originating from Algeria and 12 DNAs from Sardinia and Sicily were investigated. Their analysis revealed an association with a unique haplotype for three beta-thalassaemia mutations (-29, IVS-I-2 and IVS-I-1). It seems clear that these mutations have a unicentric origin. The presence of the -29 mutation could be explained by migration and founding effect. However, the local origin of IVS-I-2 seems clear. The four other mutations, FS6, IVS-I-6, IVS-I-110 and stop39 were found to be associated with at least two different sequence haplotypes. The likelihood of so many recurrent nucleotide dimorphisms in different lineages as a consequence of random mutation is very low; it is supported neither by the analysis of equivalent regions in other primates, nor by the presence of highly mutable sites such as CpG dinucleotides. The fact that these mutations are found exclusively in the Mediterranean area is not in favour of a recurrent origin of the mutation. The diversity is far more important for the preponderant thalassaemia mutations of the Mediterranean area and is higher in the 5' part of the beta-globin gene. Hence, the IVS-I-110, the preponderant beta-thalassaemia in the Eastern Mediterranean, probably emerged in the extension of the fertile crescent. For the stop39, all the data support the hypothesis of a West-Mediterranean origin. The diversity of haplotypes would then be generated by recombination events (crossing-over or gene conversions) between the original beta-thalassaemia chromosome and the other chomosomal structures present in the normal population.

Algeria↗

Training improves the adaptation to changing visual conditions in maintaining human posture control in a test of sinusoidal oscillation of the support.

Balance control relies on somesthetic, visual and vestibular afferences, their central processing, and adequate motor responses. We studied the consequences on postural control of the suppression of visual afferences by eye closure, during a dynamic posturographic test in six sportsmen and 14 non-sportsmen. Suppression of visual afferences during the test led to a prolongation of the pattern initially recorded with eyes open, followed by a transitory adaptive pattern, then a typical eyes closed pattern. Repetition of the test showed a progressively longer persistence of the eyes open pattern and disappearance of the adaptive one. This evolution was significantly faster in sportsmen. This progressively longer duration of the eyes open pattern may be explained by the intervention of short term memory. Our data further indicate that training improves adaptive posture control.

Adult↗