325 research outputs found
Innate immune basis for rift valley fever susceptibility in mouse models
Rift Valley fever virus (RVFV) leads to varied clinical manifestations in animals and in humans that range from moderate fever to fatal illness, suggesting that host immune responses are important determinants of the disease severity. We investigated the immune basis for the extreme susceptibility of MBT/Pas mice that die with mild to acute hepatitis by day 3 post-infection compared to more resistant BALB/cByJ mice that survive up to a week longer. Lower levels of neutrophils observed in the bone marrow and blood of infected MBT/Pas mice are unlikely to be causative of increased RVFV susceptibility as constitutive neutropenia in specific mutant mice did not change survival outcome. However, whereas MBT/Pas mice mounted an earlier inflammatory response accompanied by higher amounts of interferon (IFN)-α in the serum compared to BALB/cByJ mice, they failed to prevent high viral antigen load. Several immunological alterations were uncovered in infected MBT/Pas mice compared to BALB/cByJ mice, including low levels of leukocytes that expressed type I IFN receptor subunit 1 (IFNAR1) in the blood, spleen and liver, delayed leukocyte activation and decreased percentage of IFN-γ-producing leukocytes in the blood. These observations are consistent with the complex mode of inheritance of RVFV susceptibility in genetic studies
How the mouse has become, timidly, a model for animal and human genetic research
Depuis le dĂ©but du vingtiĂšme siĂšcle, le modĂšle souris est lâun des plus communĂ©ment utilisĂ©s par les
généticiens. Cet article retrace les origines des recherches en Génétique de la Souris, et présente ses
liens avec les travaux les plus actuels en Biologie expérimentale. AprÚs les premiÚres analyses formelles
par Lucien Cuénot, William E. Castle, Clarence C. Little, et John B. S. Haldane, les généticiens se sont
lancĂ©s dans la production de lignĂ©es consanguines. Cette histoire se prolonge jusquâĂ nos jours avec
la production de nouvelles populations de référence présentant une diversité génétique trÚs élevée :
le Collaborative Cross, et le Diversity Outbred. Dans le mĂȘme temps, Leroy Stevens, Martin Evans, Gail
Martin, et Barry Pierce rĂ©alisent une sĂ©rie dâexpĂ©riences cruciales sur une tumeur rare : le tĂ©ratocarcinome.
Ces tumeurs vont ĂȘtre placĂ©es au coeur de recherches passionnantes qui se poursuivent de
nos jours encore avec les travaux qui visent à comprendre les mécanismes de la reprogrammation des
cellules somatiques adultes en cellules pluripotentes.From the early twentieth century onwards, the mouse is one the most popular model amongst geneticists.
This article dedicates the origins of scientific work on mouse genetics and reports their links
with current research in experimental biology. Following the first formal analyses by Lucien Cuénot,
William E. Castle, Clarence C. Little, and John B. S. Haldane, geneticists plunged into the production of
inbred strains. This history continues today with the development of new resource populations with
high levels of genetic diversity: the Collaborative Cross, and the Diversity Outbred. At the same time,
Leroy Stevens, Martin Evans, Gail Martin, and Barry Pierce performed a series of crucial experiments
on a rare tumour: testicular teratocarcinoma. These tumours became the focus of a great deal of
research that continues today through the works aimed at understanding the mechanisms of somatic
adult cell reprogramming into pluripotent cells
Control of organ sizes : genetics andpathophysiology of intestinal lengthening in mouse strains
The mechanisms controlling the body size of adult mammals are well known. By contrast, even though
zoologists have examined this question since the 19th century, little is still known on the mechanisms controlling
the size of organs or tissues. The study of variants in mice, obtained either spontaneously or generated
on purpose, could provide a lead to understand and dissect these mechanisms. This paper shows
through a few chosen examples the conceptual and practical difficulties associated with this strategy.Les mécanismes qui contrÎlent
la taille du corps des mammifĂšres adultes sont aujourd'hui bien connus. Par comparaison, peu
de choses sont connues sur les mécanismes qui contrÎlent la taille des organes et des
tissus, bien que cette question intéresse les zoologistes depuis le XIXe siÚcle. L'étude
de variants, spontanés ou fabriqués à façon chez la souris, pourrait fournir un fil d'Ariane
pour identifier et disséquer les mécanismes sous-jacents. Cet article montre, à travers
quelques exemples choisis, les difficultés conceptuelles et pratiques posées par cette
approche
Initial clinical experience with the pulsed solid-state thulium YAG laser from Dornier during RIRS: first 25 cases
Introduction Holmium:yttriumâaluminiumâgarnet (Ho:YAG) and thulium fiber (TFL) lasers are currently the two laser
sources recommended for endocorporeal laser lithotripsy (ELL). Recently, the pulsed-thulium:YAG (Tm:YAG) laser was
also proposed for ELL, as an answer to both Ho:YAG and TFL limitations. We aimed to evaluate the efficiency, safety, and
laser settings of Tm:YAG laser in ELL during retrograde intrarenal surgery (RIRS).
Methods A prospective study of the first 25 patients with ureteral and renal stones who underwent RIRS using the Thulio
(pulsed-Tm:YAG, Dornier©, Germany) was performed in a single center. 272 Όm laser fibers were used. Stone size, stone
density, laser-on time (LOT) and laser settings were recorded. We also assessed the ablation speed (mm 3 /s), Joules/mm 3 and
laser power (W) values for each procedure. Postoperative results, such as stone-free rate (SFR) and zero fragments rate (ZFR)
were also recorded.
Results A total of 25 patients were analyzed (Table 1). The median (IQR) age was 55 (44â72) years old. Median (IQR) stone
volume was 2849 (916â9153)mm3
. Median (IQR) stone density was 1000 (600â1174)HU. Median (IQR) pulse energy, pulse
rate and total power were 0.6 (0.6â0,8)J, 15(15â20)Hz and 12(9â16)W, respectively. All procedures used âCaptive Frag-
mentingâ pulse modulation (Table 2). The median (IQR) J/mm 3 was 14,8 (6â21). The median (IQR) ablation rate was 0,75
(0,46â2)mm 3 /s. One postoperative complications occurred (streinstrasse). SFR and ZFR were 95% and 55%, respectively.
Conclusion The pulsed-Tm:YAG laser is a safe and effective laser source for lithotripsy during RIRS, using low pulse energy
and low pulse frequency
Centronuclear myopathy in labrador retrievers: a recent founder mutation in the PTPLA gene has rapidly disseminated worldwide
Centronuclear myopathies (CNM) are inherited congenital disorders characterized by an excessive number of internalized nuclei. In humans, CNM results from ~70 mutations in three major genes from the myotubularin, dynamin and amphiphysin families. Analysis of animal models with altered expression of these genes revealed common defects in all forms of CNM, paving the way for unified pathogenic and therapeutic mechanisms. Despite these efforts, some CNM cases remain genetically unresolved. We previously identified an autosomal recessive form of CNM in French Labrador retrievers from an experimental pedigree, and showed that a loss-of-function mutation in the protein tyrosine phosphatase-like A (PTPLA) gene segregated with CNM. Around the world, client-owned Labrador retrievers with a similar clinical presentation and histopathological changes in muscle biopsies have been described. We hypothesized that these Labradors share the same PTPLA<sup>cnm</sup> mutation. Genotyping of an international panel of 7,426 Labradors led to the identification of PTPLA<sup>cnm</sup> carriers in 13 countries. Haplotype analysis demonstrated that the PTPLA<sup>cnm</sup> allele resulted from a single and recent mutational event that may have rapidly disseminated through the extensive use of popular sires. PTPLA-deficient Labradors will help define the integrated role of PTPLA in the existing CNM gene network. They will be valuable complementary large animal models to test innovative therapies in CNM
Innate immune basis for rift valley fever susceptibility in mouse models
Rift Valley fever virus (RVFV) leads to varied clinical manifestations in animals and in humans that range from moderate fever to fatal illness, suggesting that host immune responses are important determinants of the disease severity. We investigated the immune basis for the extreme susceptibility of MBT/Pas mice that die with mild to acute hepatitis by day 3 post-infection compared to more resistant BALB/cByJ mice that survive up to a week longer. Lower levels of neutrophils observed in the bone marrow and blood of infected MBT/Pas mice are unlikely to be causative of increased RVFV susceptibility as constitutive neutropenia in specific mutant mice did not change survival outcome. However, whereas MBT/Pas mice mounted an earlier inflammatory response accompanied by higher amounts of interferon (IFN)-α in the serum compared to BALB/cByJ mice, they failed to prevent high viral antigen load. Several immunological alterations were uncovered in infected MBT/Pas mice compared to BALB/cByJ mice, including low levels of leukocytes that expressed type I IFN receptor subunit 1 (IFNAR1) in the blood, spleen and liver, delayed leukocyte activation and decreased percentage of IFN-γ-producing leukocytes in the blood. These observations are consistent with the complex mode of inheritance of RVFV susceptibility in genetic studies
Comparaison in vitro de lâefficacitĂ© statique ou dynamique des lasers Holmium :YAG et thulium fibrĂ© pour la lithotritie endocorporelle : impact de la vitesse de dĂ©placement
La vitesse optimale de dĂ©placement (VOD) de la fibre laser pour rĂ©aliser la pulvĂ©risation lithiasique est une variable inconnue Ă ce jour, autant pour le laser thulium fibrĂ© (TFL) que pour le laser Holmium :YAG (Ho :YAG). Lâobjectif Ă©tait de dĂ©terminer in vitro la VOD de la fibre laser lors dâune lithotritie endocorporelle en fonction des paramĂštres laser avec le TFL et lâHo :YAG, au moyen des volumes dâablation (VA).Bourse de Recherche AFU 201
Analyse in vitro de lâefficacitĂ© de la lithotritie laser : quel modĂšle utiliser ?
LâĂ©tude in vitro de la lithotritie laser (LL) utilise des calculs humains (CH) ou synthĂ©tiques (CS). Devant lâaugmentation de la pulvĂ©risation laser (Dusting), peu dâĂ©chantillons humains sont disponibles. Les CS sont donc privilĂ©giĂ©s, confectionnĂ©s par mĂ©lange dâeau et de plĂątre, avec la problĂ©matique de leur rĂ©hydratation lors des LL. Lâobjectif Ă©tait de comparer les volumes dâablation (VA) entre CS homogĂšnes (CSHo) ou hĂ©tĂ©rogĂšnes(CSHe), et par rapport au poids ablatĂ© (PA).Bourse de Recherche AFU 201
Medium to long term follow up study of the efficacy of cessation of eye-rubbing to halt progression of keratoconus
PurposeTo study the progression of keratoconus after cessation of eye rubbing with a minimum follow up of three-years.DesignRetrospective, monocentric, longitudinal cohort study of keratoconus patients with a minimum of 3 years follow-up.ParticipantsOne hundred fifty three eyes of seventy-seven consecutive patients with keratoconus were included.MethodsInitial examination consisted of anterior and posterior segment evaluation using slit-lamp biomicroscopy. At the initial visit, patients were thoroughly informed of their pathology and instructed to stop rubbing their eyes. Eye rubbing cessation was assessed at all the follow-up visits at 6âmonths, 1âyear, 2âyears, 3âyears, and yearly afterward. Corneal topography using the PentacamÂź (OculusÂź, Wetzlar, Germany) was used to obtain maximum and average anterior keratometry readings (Kmax and Kmean), as well as thinnest pachymetry (Pachymin, ÎŒm) in both eyes.Main outcome measuresThe main outcomes measured were maximum keratometry (Kmax), mean keratometry (Kmean), and thinnest pachymetry (Pachymin) values at various time points to assess for keratoconus progression. Keratoconus progression was defined as a significant augmentation of Kmax (>1D), Kmean (>1D), or significant diminution of Pachymin (>5%) throughout the total follow-up duration.ResultsOne hundred fifty three eyes of seventy-seven patients (75.3% males) aged 26.4âyears old, were followed for an average of 53âmonths. Over the course of the follow-up, there was no statistically significant variation of âKmax (+0.04â±â0.87; pâ=â0.34), â Kmean (+0.30â±â0.67; pâ=â0.27) nor âPachymin (â4.36â±â11.88; pâ=â0.64). Among the 26 of the 153 eyes which had at least one criterion of KC progression, 25 admitted continuing eye rubbing, or other at-risk behaviors.ConclusionThis study suggests that a significant proportion of keratoconus patients are likely to remain stable if close monitoring and strict ARB cessation are achieved, without the need for further intervention
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