Contribution à l'étude de mélanomes cutanés canins : recherche de critères histologiques et immunohistochimiques pronostiqués à partir d'un echantillon de 65 cas.

Les mélanomes cutanés canins représentent 6 à 9% des tumeurs de la peau dans cette espèce. Malgré l'existence d'une classification pronostique établie par Bostock en 1979, basée sur le nombre de mitoses dans la population néoplasique, l'histopronostic rendu après examen anatomopathologique est souvent considéré comme aléatoire. Aucun critère architectural ou cytologique autre que l'index mitotique n'a pour l'instant été intégré de façon formelle à l'établissement du pronostic des mélanomes cutanés du chien. L'utilisation de marqueurs immunologiques tels que les antigènes de prolifération nucléaire (exemple : épitope Ki-67) a permis d'améliorer, chez le chien comme chez l'homme, la qualité du pronostic rendu. Plus récemment, des immunomarqueurs rendant compte de l'état de différenciation (Melan A) ou des capacités d'adhésion à la matrice extracellulaire (CD44) des cellules mélaniques tumorales, ont été proposés en médecine humaine comme facteurs influençant le pronostic. Dans cette étude, à partir d'un échantillon de 65 cas de mélanomes cutanés canins suivis sur une période post-opératoire minimale de 12 mois, nous avons étudié 16 critères architecturaux et cytologiques différents ainsi que l'expression des trois marqueurs immunologiques : épitope Ki-67, CD44 et Melan A. Nous proposons différents critères histologiques, majeurs et mineurs, pouvant influencer le pronostic de la lésion, ainsi qu'une démarche raisonnée permettant d'intégrer les données des marquages Ki-67 et CD44 dans l'établissement de celui-ci

Régulation des populations de Nématodes gastro-intestinaux (Haemonchus contortus et Trichostrongylus colubriformis) dans deux races ovines, INRA 401 et Barbados Black Belly.

Les Nématodes gastro-intestinaux sont des parasites majeurs en élevage ovin. Actuellement, leur contrôle repose sur l'utilisation de molécules anthelminthiques. L'extension de résistances à ces molécules dans les populations de strongles rend urgente la recherche de solutions alternatives comme la sélection d'animaux résistants. Toutefois, la méconnaissance des mécanismes de la réponse immunitaire des ovins contre ces strongles reste un obstacle à son développement. La première partie de nos travaux a démontré une orientation Th2 claire lors d'infestation par Haemonchus contortus et plus équivoque lors d'infestation par Trichostrongylus colubriformis. Dans un second temps, les réponses immunes adaptatives de moutons de race sensible (INRA 401) et résistante (Barbados Black Belly) lors d'infestation par H. contortus ont été comparées. Des différences d'expression des gènes de l'IL-4, IL-5 et de l'IL-13, et d'éosinophilie sanguine ont été enregistrées entre les deux races. ABSTRACT : Gastrointestinal nematodes are major parasites of sheep industry. Current control is mainly based on chemical molecules. Due to the extension of anthelmintic resistance in nematode populations all around the world, alternative strategies, such as selective breeding of resistant sheep, are now necessary. Nevertheless, the imprecise knowledge of sheep immune mechanisms towards these parasites limits their development. The first part of this study demonstrated a clear Th2 polarization of the sheep immune response to Haemonchus contortus infection. In another hand, the response to Trichostrongylus colubriformis was more equivocal. In a second time, adaptative immune responses to H. contortus infection were compared between a susceptible breed (INRA 401) and a resistant one (Barbados Black Belly). Differences in IL-4, IL-5 and IL-13 gene expressions and blood eosinophilia were noticed between the two breeds

Highly Efficient Prion Transmission by Blood Transfusion

It is now clearly established that the transfusion of blood from variant CJD (v-CJD) infected individuals can transmit the disease. Since the number of asymptomatic infected donors remains unresolved, inter-individual v-CJD transmission through blood and blood derived products is a major public health concern. Current risk assessments for transmission of v-CJD by blood and blood derived products by transfusion rely on infectious titers measured in rodent models of Transmissible Spongiform Encephalopathies (TSE) using intra-cerebral (IC) inoculation of blood components. To address the biological relevance of this approach, we compared the efficiency of TSE transmission by blood and blood components when administrated either through transfusion in sheep or by intra-cerebral inoculation (IC) in transgenic mice (tg338) over-expressing ovine PrP. Transfusion of 200 µL of blood from asymptomatic infected donor sheep transmitted prion disease with 100% efficiency thereby displaying greater virulence than the transfusion of 200 mL of normal blood spiked with brain homogenate material containing 103ID50 as measured by intracerebral inoculation of tg338 mice (ID50 IC in tg338). This was consistent with a whole blood titer greater than 103.6 ID50 IC in tg338 per mL. However, when the same blood samples were assayed by IC inoculation into tg338 the infectious titers were less than 32 ID per mL. Whereas the transfusion of crude plasma to sheep transmitted the disease with limited efficacy, White Blood Cells (WBC) displayed a similar ability to whole blood to infect recipients. Strikingly, fixation of WBC with paraformaldehyde did not affect the infectivity titer as measured in tg338 but dramatically impaired disease transmission by transfusion in sheep. These results demonstrate that TSE transmission by blood transfusion can be highly efficient and that this efficiency is more dependent on the viability of transfused cells than the level of infectivity measured by IC inoculation

Transgenic Mice Expressing Porcine Prion Protein Resistant to Classical Scrapie but Susceptible to Sheep Bovine Spongiform Encephalopathy and Atypical Scrapie

Atypical scrapie strain phenotypes may shift when transmitted to a new host

Endocarditis in Cattle Caused by Bartonella bovis

This study aimed to determine the role of Bartonella as an endocarditis agent in cattle. Bartonella bovis was identified by PCR, gene sequences analysis, and specific internal transcribed spacer amplicon product size in 2 bovine endocarditis cases with high antibody titers, which demonstrates that B. bovis is a pathogen for cattle

Distribution and quantitative estimates of variant Creutzfeldt Jakob Diseases prions in the tissues of clinical and asymptomatic patients

In the United-Kingdom, ≈1 of 2,000 persons could be infected with variant Creutzfeldt-Jakob disease (vCJD). Therefore, risk of transmission of vCJD by medical procedures remains a major concern for public health authorities. In this study, we used in vitro amplification of prions by protein misfolding cyclic amplification (PMCA) to estimate distribution and level of the vCJD agent in 21 tissues from 4 patients who died of clinical vCJD and from 1 asymptomatic person with vCJD. PMCA identified major levels of vCJD prions in a range of tissues, including liver, salivary gland, kidney, lung, and bone marrow. Bioassays confirmed that the quantitative estimate of levels of vCJD prion accumulation provided by PMCA are indicative of vCJD infectivity levels in tissues. Findings provide critical data for the design of measures to minimize risk for iatrogenic transmission of vCJD

Similar Biochemical Signatures and Prion Protein Genotypes in Atypical Scrapie and Nor98 Cases, France and Norway

Similarities raise questions regarding the origin of these recently described cases

Beyond PrPres Type 1/Type 2 Dichotomy in Creutzfeldt-Jakob Disease

Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrPres and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrPSc) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrPres were identified. Despite this, the other two biochemical assays found that PrPSc from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrPSc subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrPres pattern. The identification of four different PrPSc biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability

Classic Scrapie in Sheep with the ARR/ARR Prion Genotype in Germany and France

We report 2 natural scrapie cases in sheep carrying the ARR/ARR prion genotype, which is believed to confer resistance against classic scrapie and bovine spongiform encephalopathy