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Biomedical subjects

A Provost

Publications and source records attributed to A Provost.

At least 19 recordsLinked to original sources

Metabolic design of macroscopic bioreaction models: application to Chinese hamster ovary cells.

The aim of this paper is to present a systematic methodology to design macroscopic bioreaction models for cell cultures based upon metabolic networks. The cell culture is seen as a succession of phases. During each phase, a metabolic network represents the set of reactions occurring in the cell. Then, through the use of the elementary flux modes, these metabolic networks are used to derive macroscopic bioreactions linking the extracellular substrates and products. On this basis, as many separate models are obtained as there are phases. Then, a complete model is obtained by smoothly switching from model to model. This is illustrated with batch cultures of Chinese hamster ovary cells.

Animals↗

In vivo adenovirus-mediated delivery of a uPA/uPAR antagonist reduces retinal neovascularization in a mouse model of retinopathy.

Diabetic retinopathy and retinopathy of prematurity are among the leading causes of vision impairment throughout the world. Both diseases are characterized by pathological angiogenesis, which severely impairs vision. Extracellular proteinases play important roles in endothelial cell migration during angiogenesis. Amino-terminal fragment (ATF) is an angiostatic molecule that targets the uPA/uPAR system and inhibits endothelial cell migration. The angiostatic effect of ATF has been demonstrated in models of cancer, but has never been assessed in pathological retinal neovascularization. Endostatin also has angiostatic effects on tumor growth and retinal neovascularization. We used an adenoviral vector carrying the murine ATF (AdATFHSA) or endostatin gene coupled to human serum albumin (HSA) (AdEndoHSA) to increase the half-life of the therapeutic protein in the circulation. We induced retinopathy by exposing 7-day-old mice to high levels of oxygen. They were intravitreally injected with the vectors. Local injection of AdATFHSA or AdEndoHSA reduced retinal neovascularization by 78.1 and 79.2%, respectively. Thus, the adenovirus-mediated delivery of ATFHSA or EndoHSA reduces retinal neovascularization in a mouse model of hypoxia-induced neovascularization.

Adenoviruses, Human↗

Contagious bovine pleuropneumonia vaccines, historic highlights, present situation and hopes.

Contagious bovine pleuropneumonia (CBPP) is a contagious infection of cattle caused by a mycoplasma, M. mycoides subsp. mycoides SC (MmmSC). It induces lesions of pleuropneumonia in acute cases and the formation of pulmonary "sequestra" in chronic cases. The disease is prevalent mostly in Africa, where it is responsible for high losses, but it has also been sporadically present in Southern Europe until 1999. Vaccination is now prohibited in most countries except in Africa. An empirical "inoculation" procedure was developed as early as 1852 in Europe but it may have been used even earlier in Africa. The inoculation of pleural fluid was performed at the tip of the tail in Europe and on the bridge of the nose in Africa. It conferred good protection but induced a high number of fatal cases. Various inactivated preparations have been tested in the past with inconclusive results leading sometime to some protection and some other time to a sensitisation of the immunised animals. Such preparations have never been used in the field. Attenuated MmmSC strains have been developed in the 1950s and used extensively in the field both in Africa and Australia. The best known vaccine strains are KH3J, T1/44 and T1sr. Vaccination campaigns have succeeded in reducing considerably the CBPP prevalence in these two continents but eradication was achieved in Australia only by switching to strict measures of animal movement control and a stamping-out policy. The search for new CBPP vaccines has become a major issue for African countries that are facing an increase in outbreaks. The rationale for this search is based on a better understanding of the mycoplasma virulence mechanisms that could lead to a targeted attenuation of MmmSC strains. It is also based on a better understanding of the bovine immune response that may be driven to a pathogenic inflammatory response or conversely to a better balanced response leading to protection.

Africa↗

Contagious bovine pleuropneumonia. A reassessment of the efficacy of vaccines used in Africa.

Contagious bovine pleuropneumonia is a major threat for cattle in Africa. Since 1956 the T1/44 strain has been used as a vaccine, and later on, T1sr, a streptomycin-resistant variant that gives fewer post-vaccinal reactions had been developed. These vaccines are known not to be very efficient but they normally should provide protection for about eight months. However, recent emergency vaccinations, performed in various countries in the southern part of the continent apparently met with failure, casting doubts on the identity as well as the protection afforded by the T1sr strain. A vaccine trial has been designed to reassess the real protection afforded by these vaccines in face of recently isolated pathogenic strains. Great care has been taken to test the original vaccinal strains at a dose corresponding to the minimum requirement by international standards. The test was performed in Cameroon, Kenya, and Namibia as to take into account the genetic diversity that exists among the pathogenic strains. In those conditions, the protection rate at three months varied from 33 to 67%, whatever the strain used, T1/44 or T1sr. These results call for additional research for vaccine development and careful planning of strategies in the fight against CBPP.

Africa↗

[Strategies for prevention and eradication of contagious bovine pleuropneumonia with or without vaccination].

Contagious bovine pleuropneumonia (CBPP) offers, like rinderpest, the paradox of having been eradicated from some countries (north-western Europe, the United States of America) before the nature of the pathogenic agent was known. As a preventive measure, inoculation of pathogenic material was used but success varies due to strategic inadequacies. The same applies to vaccination with more or less attenuated live strains of Mycoplasma mycoides subsp. mycoides. Many ideas for prophylaxis have been suggested. Disease-free countries must apply the recommendations of the International Animal Health Code of the Office International des Epizooties (OIE), including those concerning the operation of epidemiological surveillance systems. Infected countries (or regions) select one of the following courses of action, depending on epidemiological, geographic, economic and social circumstances: Slaughter of affected and in-contact animals. This radical, simple and effective solution cannot be applied everywhere, particularly in a number of developing countries which have pastoral economies. Slaughter of affected animals and vaccination of those in contact. This method, which actually perpetuates the infection, is unfortunately still used widely. Preventive vaccination of healthy animals, coupled with the slaughter of affected animals and/or revaccination of those exposed to infection. This method controls the situation if outbreaks are detected efficiently and combated energetically. The tactical approach for disease-free and infected areas should continue to be that of large-scale and repeated vaccination, recommended since 1970 and the efficiency of which has been proved. This approach can lead to eradication when maintained for at least three years and applied to an entire infected region or country. A country is recognised as free from infection under rules adopted by the OIE in 1995.

Animals↗

Measuring recovery from general anaesthesia using critical flicker frequency: a comparison of two methods.

Critical flicker frequency (CFF) is the frequency at which a flickering light appears steady. It is a sensitive measure for assessing recovery from anaesthesia. The CFF is almost always determined with the method of limits by which the flickering frequency is progressively decreased (or increased) until the patient reports a change from fusion to flicker (or flicker to fusion). This method has two disadvantages: it is influenced by the response bias (i.e., the subjective criterion used by the subject to decide that flicker is present or absent) and by the response delay (i.e., the interval between the perceptual change and the response). To avoid these problems, the method of forced choice is recommended. For each trial, the subject observes the light during two short successive periods. The light flickers during only one period, according to chance. The patient must indicate the period during which flickers occur. If uncertain, the patient has to make a guess. The aim of this study was to compare the two methods for assessing recovery from general anaesthesia. Two induction agents were used to obtain different recovery profiles. Twenty patients undergoing uncomplicated surgery lasting less than two hours were tested. They received either thiopentone or midazolam for induction, according to a randomized design. Vecuronium was used to facilitate tracheal intubation and anaesthesia was maintained with fentanyl, isoflurane and nitrous oxide. The CFF was measured before induction and at 60, 120 and 180 minutes after arrival in the recovery room. The person measuring CFF was unaware of the induction agent used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Attenuation of a strain of rinderpest virus: potential homologous live vaccine].

Peste des petits ruminants (PPR) is a highly contagious disease of small ruminants frequently associated with severe mortality in these hosts. In countries where it occurs, PPR represents an important constraint to the improved productivity of sheep and goats. Until now the only way to combat this plague has been the use of heterologous rinderpest vaccine; all attempts to develop a homologous vaccine have ended in failure. The present communication describes the attenuation of the Nigerian strain PPRV Nig 75/1 by serial passage in Vero cells. The avirulent virus obtained has the same characteristics as Plowright and Ferris' rinderpest vaccine. The virus is advanced as a potential homologous vaccine against PPR.

Animals↗

The historical background and global importance of heartwater.

The first written record of what probably could have been heartwater originates from South Africa and dates back to 1838. Since then, the disease was described from almost all the African countries south of the Sahara as well as from Madagascar, São Tome, Reunion, Mauritius and a number of islands in the Caribbean. Most research on the disease, at least until recently, was conducted in South Africa. Progress in research was slow but a few outstanding findings are mentioned in this paper. Despite inadequate information on its actual economic impact on livestock production, it is generally accepted that heartwater is either the most or second most important tick-borne disease in Africa. Depending on the area, heartwater ranks either second or third amongst diseases such as East Coast fever, tsetse-transmitted trypanosomiasis, rinderpest and perhaps also schistosomiasis. Heartwater is a major obstacle with regard to the introduction of highly producing animals intended for the upgrading of local breeds. Furthermore, it remains a major threat to areas such as the American mainland, where potential vectors are present but where the disease does not occur.

Animals↗

[Problems in production, control and utilization of veterinary vaccines in the developing countries].

For a whole series of reasons, most of which are political, the developing countries are following a policy of national self-sufficiency in veterinary vaccines. They are faced with problems at various levels: (1) at the level of logistic distribution, the developing countries suffer from a shortage of trained personnel, frequently lacking in enthusiasm, an often chronic shortage of funds; poorly equipped premises; poor maintenance of sophisticated but indispensable equipment (e.g. freeze-driers); a lack of facilities for cold storage and of distribution channels; field personnel with limited experience; (2) at the level of production, they must contend with difficulties in obtaining supplies of flasks and glassware; irregular supplies of water and electricity; difficulties in obtaining susceptible animals for quality control. The developing countries have found basically pragmatic solutions to these problems, such as the strict separation of the sites, materials and personnel involved in routine diagnosis and those involved in production; temporary foreign technical assistance, with or without financial aid; the use of simple, unsophisticated techniques, which are known to be reliable, even if somewhat outdated; manufacturing in bulk in multiple-dose bottles; research into the thermostabilisation of vaccine strains and the development of thermoprotective diluents for freeze-drying and reconstitution; the extensive use of combined vaccines; the establishment of production and control standards under the auspices of the WHO/FAO/OIE. In spite of these obstacles, the cost price is particularly low (from 0.20 to 0.35 francs per dose), which compares favourably with that of foreign private industry.

Africa↗

[Combined vaccines in veterinary medicine in the developing countries].

It is in the interest of developing countries to have combined vaccines in veterinary medicine, not so much because they reduce production costs, but rather because they increase convenience and efficacy concerning the logistics of prophylactic projects in the field, thus lowering the cost of these projects. Their drawbacks are basically due to the biological compatibility of immunogens (possible immunosuppression by some viruses) and to the interaction of the various components when mixed, or when lyophilization is carried out. Some examples of such associations of vaccines are: (1) cattle plague + pleuropneumonia and possibly anthrax, (2) anthrax + blackleg, (3) sheeppox + anthrax, (4) pleuropneumonia + blackleg, (5) Newcastle disease + fowlpox + fowl typhoid, (6) fowl typhoid + chicken pasteurellosis. Practical results have been most positive and include the eradication of cattle plague - a major scourge of almost all of the African continent - and control over peripneumonia as a first step towards its eradication.

Africa↗

Recombination after protoplast fusion in the yeast Candida tropicalis.

Candida tropicalis protoplasts obtained by snail enzyme treatment were induced to fuse by the use of polyethylene-glycol. Heterokaryons formed by two auxotrophic strains were selected by complementation on minimal medium. These heterokaryons were unstable and readily dissociated into their nuclear components. Under appropriate conditions, the parental nuclei of an heterokaryon fused. The homokaryon so obtained was unstable and segregated into various types of auxotrophic and prototrophic recombinants.

Candida↗