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On the basis of previous occasional findings, the Fischer indole cyclization of ten ketone phenylhydrazones containing moieties of increasing bulkiness was investigated in order to isolate eventual side products. In the cases of the three 2, 3 and 4acetylpyridine phenylhydrazones the corresponding 2pyridylindoles were the sole compounds so far isolated. In all the remaining cases, beside the indoles a mixture of basic compounds was obtained. In all cases aniline and a 2substituted 2methyl or 2phenylbenzimidazole were formed, the last resulting through an apparent orthosemidinic rearrangements of phenylhydrazones. Starting from methyl isopropyl ketone phenylhydrazone a compound of formula C11H15NO was also isolated, to which the structure of 34aminophenyl3methylbutanone was assigned on the basis of ir, nmr spectra and of the chemical reactivity. The formation of this compound seems related to a parabenzidinelike rearrangement of phenyl hydrazone.

During the course of a study aimed at the search for new potent aromatase inhibitors, several new androstenedione analogs were synthesized and evaluated. This study led to the discovery of 19-[(methylthio)methyl]androsta-4,9(11)-diene-3,17-dione (7; RU54115) already described by our laboratory. The object of the present series of papers is to disclose the result of the structure−activity relationship studies that gave rise to this compound. This first part deals mainly with the substitution in the 19-position of the steroid nucleus. Several parameters were varied, the length of the chain and its rigidity and branching, as well as the nature of the heteroatom itself and its substitution. The interaction of these new compounds with human placental aromatase in competition with the substrate androstenedione was studied by difference visible spectroscopy. The in vivo aromatase-inhibiting activities were evaluated by measuring the estradiol lowering after oral administration of the compounds to PMSG-primed female rats.

vgfis a neurotrophin response-specific, developmentally regulated gene that codes for a neurosecretory polypeptide. Its transcription in neuronal cells is selectively activated by the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor, and neurotrophin 3, which induce survival and differentiation, and not by epidermal growth factor. We studied a short region of the rat vgfpromoter which is essential for its regulated expression. A cyclic AMP response element (CRE) within this region is necessary for NGF induction of vgftranscription. Two sites upstream of CRE, an E box and a CCAAT sequence, bind nuclear protein complexes and are involved in transcriptional control. The E box has a dual role. It acts as an inhibitor in NIH 3T3 fibroblasts, together with a second E box located downstream, and as a stimulator in the NGF-responsive cell line PC12. By expression screening, we have isolated the cDNA for a basic helix-loop-helix transcription factor, a homolog of the HTF4/HEB E protein, that specifically binds the vgfpromoter E box. The E protein was present in various cell lines, including PC12 cells, and was a component of a multiprotein nuclear complex that binds the promoter in vitro. The E box and CRE cooperate in binding to this complex, which may be an important determinant for neural cell-specific expression.

The gas-phase hydrolysis of TiCl4 has been studied with several laboratory reactors. Unexpectedly, the reaction is clearly split in two steps, an almost instantaneous partial hydrolysis which produces 2 mol of HCl/mol of TiCl4 together with a salt, identified as Ti(OH)2Cl2. The latter forms a very fine dust which easily evolves into aerosols. Ti(OH)2Cl2 in a moist environment eventually hydrolyses to HCl. The kinetics of both steps have been studied. While the first step is very fast, the salt hydrolysis is much slower, its kinetics being controlled by diffusion of the gaseous reactant through the shell of the solid product covering the aerosol particles.

The hydrogenation of organic substrates in a fixed-bed catalytic reactor is considered, using supercritical CO2as a solvent to increase the solubility of hydrogen in the liquid reactants. Reaction rates can be adjusted by changing operating conditions, allowing the reaction volume to be much smaller than in conventional processes. Although it is possible to perform the reaction in a homogenous phase, to avoid interphase mass-transfer limitations, extremely high temperature and pressure may be needed to reach such a condition; therefore the reaction is carried out at conditions where both a gas and a liquid phase are present. Taking into account the solid catalyst, a three-phase reaction system has to be delat with.

Catalytic hydrogenation in supercritical carbon dioxide has been studied. Experimental results and theoretical calculations are presented, attempting to elucidate the effects of temperature, pressure, and CO2 concentration on the rate of reaction. An effort has been made to develop a procedure to test catalytic reactions in supercritical fluids in view of future industrial applications. Hydrogenation rates of the two double bonds of an unsaturated ketone on a commercial alumina-supported palladium catalyst were measured in a continuous gradientless internal-recycle reactor at different temperatures, pressures, and CO2-to-feed ratios. A Berty-type reactor has been suitably modified for use with supercritical solvents. The accurate control of the organic, carbon dioxide, and hydrogen feed flow rates and of the temperature and pressure inside the reactor provided reproducible values of the product stream compositions, which were measured on-line after separation of the gaseous components. In order to develop a kinetic model, vapor−liquid equilibrium calculations were carried out through a Peng−Robinson equation of state, tuned on binary high-pressure vapor−liquid equilibrium data. Compositions in the liquid phase inside the reactor were predicted, starting from the on-line analysis after depressurization. A simplified power law kinetic equation is shown to provide a good description of the experimental data.

C3H and C57 BL/6 mice carrying methylcholanthrene-induced fibrosarcomas were injected i.p. daily with histamine, metiamide (anti-histamine type-2 receptor), histamine + metiamide, mepyramine (anti-histamine type-1 receptor), serotonin and methysergide (anti-serotonin). Inhibition of tumour growth and lengthened survival were observed with histamine and histamine + metiamide. The best results (both on tumour growth and survival) were obtained with serotonin. Survival was increased by metiamide and decreased by mepyramine and methysergide. In histamine-treated and in serotonin-treated mice, histological studies of the tumours showed large and numerous foci of haemorrhagic necrosis. Stimulation of histamine type-1 or serotonin receptors and inhibition of histamine type-2 receptors play a beneficial role in the host's defence against tumours.

Tissue histamine levels were studied in C3H and C57BL/6 mice bearing a methylcholanthrene-induced fibrosarcoma, in Wag rats bearing an aflatoxin B1-induced hepatoma, and in Commentry rats bearing a grafted hepatoma. Histamine levels were significantly higher (1.5 to 3 fold) in the tumour-bearing animals for ventral and dorsal skin, skeletal muscle and stomach fundus. Total histamine content was increased in the spleen. In C3H mice with McC3-1 fibrosarcoma, the excision of the tumour or its partial regression by intratumoral injections of corynebacterium parvum induced a reversion to normal values. The tumour thus appears responsible for the increased histamine levels in tissues distant from the tumour.

Histamine levels have been determined in nine tissues of four kinds (W/Wv, Wv/+, W/+, +/+) of WBB6F1 male and female mice, and mast cells have been counted in the skin and the fundus of W/Wv and +/+ mice.

We have developed an in situ hybridization assay capable of detecting enteroviral RNA in myocardial cells, using molecularly cloned coxsackievirus B3 cDNA as a diagnostic probe. Because of the high degree of nucleic acid sequence homology among the numerous enteroviral serotypes, including the group A and B coxsackieviruses and the echoviruses, detection of these various agents commonly implicated in human viral heart disease is possible in a single hybridization assay. We demonstrate the considerable potential of this method for an unequivocal diagnosis of enteroviral heart disease as well as for pathogenicity studies. Using athymic mice persistently infected with coxsackievirus B3 as a model system, we show that the myocardium is affected in a disseminated, multifocal manner.

TheVgfgene was originally identified as a 2.7-kb cDNA fragment isolated from nerve growth factor-treated PC12 cells by differential display against PC12 cells. It is transcribed solely in subpopulations of neuroendocrine cellsin vivoand it is induced by neurotrophins in target cellsin vitro.The single-copy humanVGFgene was isolated from a genomic library. The gene spans approximately 6 kb and contains two exons. The entire VGF protein is encoded by exon 2, while exon 1 contains only 5′-untranslated sequence. The structural organization of the human gene is similar to that described for the ratVgfgene (S. R. J. Saltonet al.,1991,Mol. Cell. Biol.11: 2335–2349) and both the translated and the untranslated regions show a high degree of sequence homology to the rat gene. Northern blot analysis revealed a single transcript of approximately 2.7 kb that was detected only in mRNA preparations from brain. The gene was assigned to chromosome 7q22 by fluorescencein situhybridization.

L’exposition des employés des EFS à des particules fines et ultrafines (PF/PUF) peut induire un stress oxydant potentiellement responsable de plusieurs pathologies inflammatoires, dont la bronchopneumopathie chronique obstructive (BPCO). L’augmentation des biomarqueurs du stress oxydant à la fois au niveau systémique et local (au sein des voies respiratoires dans le cas d’une BPCO) pourrait constituer un marqueur d’intérêt pour le suivi des travailleurs exposés et le dépistage précoce des pathologies. L’exposition aux PF/PUF des employés n’étant pas exclusive des EFS, son évaluation globale, nécessite l’identification et la documentation des différents types et sources d’expositions (air extérieur, tabagisme, etc.) et leurs déterminants.

Le cancer broncho-pulmonaire est la principale cause de décès par cancer en Suisse. Environ 15 % des cancers broncho-pulmonaires est d’origine professionnelle, ce qui en fait le cancer professionnel le plus fréquent.

En avril 2020 nous avons assisté à une épidémie de méningo-encéphalite à tiques (MET) d’origine alimentaire en France. L’objectif de cet article est de décrire les caractéristiques et investigations liées à cet événement rare.

ABSTRACTKPC-type carbapenemases are emerging in Klebsiella pneumoniaeand other Gram-negative pathogens worldwide. Rapid and sensitive detection of these resistance determinants has become relevant to clinical management and infection control. We evaluated the bioMérieux EasyQ real-time PCR assay for blaKPCdetection with 300 members of the Enterobacteriaceae, including 29 control strains producing known carbapenemases and 271 nonreplicate clinical isolates. The EasyQ assay correctly detected all of the 111 isolates harboring blaKPCgenes, with no false positives, and results were available within 2 h.

AbstractThe significance of cytological evolution of alveolar cells explains differences in milk yield that resulted in a different shape of lactation curve. In this paper, investigation of cellular background for this pattern was studied morphometrically in mammary gland of dairy ewes prior to lambing to involution. The ratio of epithelial to the luminal area was greatest at 7 days from lambing, it diminished on day 30 and 60 of lactation and it increased thereafter on day 150 of lactation and on day 7 of involution. The evolution of mammary tissues shows a clear decrease in stromal mass from prepartum until 60 DIM. Structural changes of mammary tissues during late pregnancy, lactation and dry off, can be used as a basis to estimate the evolution of the number of secretory cells in dairy ewes.

AbstractAimsOccupational Burnout (OB) is currently measured through several Patient-Reported Outcome Measures (PROMs) and some of them have become widely used in occupational health research and practice. We, therefore, aimed to review and grade the psychometric validity of the five OB PROMs considered as valid for OB measure in mental health professionals (the Maslach Burnout Inventory (MBI), the Pines' Burnout Measure (BM), the Psychologist Burnout Inventory (PBI), the OLdenburg Burnout Inventory (OLBI) and the Copenhagen Burnout Inventory (CBI)).MethodsWe conducted systematic literature searches in MEDLINE, PsycINFO and EMBASE databases. We reviewed studies published between January 1980 and September 2018 following a methodological framework, in which each step of PROM validation, the reference method, analytical technics and result interpretation criteria were assessed. Using the COnsensus-based Standards for the selection of health Measurement Instruments we evaluated the risk of bias in studies assessing content and criterion validity, structural validity, internal consistency, reliability, measurement error, hypotheses testing and responsiveness of each PROM. Finally, we assessed the level of evidence for the validity of each PROM using the GRADE approach.ResultsWe identified 6541 studies, 19 of which were included for review. Fifteen studies dealt with MBI whereas BM, PBI, OLBI and CBI were each examined in only one study. OLBI had the most complete validation, followed by CBI, MBI, BM and PBI, respectively. When examining the result interpretation correctness, the strongest disagreement was observed for MBI (27% of results), BM (25%) and CBI (17%). There was no disagreement regarding PBI and OLBI. For OLBI and CBI, the quality of evidence for sufficient content validity, the crucial psychometric property, was moderate; for MBI, BM and PBI, it was very low.ConclusionTo be validly and reliably used in medical research and practice, PROM should exhibit robust psychometric properties. Among the five PROMs reviewed, CBI and, to a lesser extent, OLBI meet this prerequisite. The cross-cultural validity of these PROMs was beyond the scope of our work and should be addressed in the future. Moreover, the development of a diagnostic standard for OB would be helpful to assess the sensitivity and specificity of the PROMs and further reexamine their validity.The study protocol was registered in PROSPERO (CRD 42019124621).

During 2003–2005, 399 abortion samples (315 fetuses and 84 placentae) were collected from 107 ovine and caprine farms in northern Sardinia. Tissues from aborted fetuses and placentae were examined by PCR assay to detect DNA from Coxiella burnetii, Chlamydophila abortus, Salmonella enterica Serovar abortusovis, Toxoplasma gondii, and Neospora caninum.The DNA from at least 1 of these 5 infectious agents was amplified in 41% of ovine fetuses, while only 17% of the caprine fetuses yielded a positive amplification result for at least 1 of the 5 agents. Out of a total of 366 ovine aborted samples, T. gondiiDNA was detected most frequently (18.1% of fetuses and 13.1% of placentae), followed by S. abortusovis(13% of fetuses and 14.4% of placentae), C. burnetii(10.9% of fetuses, of 9.2% placentae), C. abortus(2.4% of fetuses, 6.5% of placentae), and N. caninum(2% of placentae). In 33 fetuses and 9 placentae, the simultaneous presence of pathogens with different associations was detected. Out of a total of 31 caprine aborted samples, T. gondiiwas detected most frequently (13% of fetuses and 25% of placentae), followed by C. abortus(12.5% of placentae), C. burnetii(12.5% of placentae), and N. caninum(8.6%).

Background: Haematopoietic stem cells (HSCs) first arise during development in the aorta-gonad-mesonephros (AGM) region of the embryo from a population of haemogenic endothelial cells which undergo endothelial-to-haematopoietic transition (EHT). Despite the progress achieved in recent years, the molecular mechanisms driving EHT are still poorly understood, especially in human where the AGM region is not easily accessible. Results: In this study, we take advantage of a human pluripotent stem cell (hPSC) differentiation system and single-cell transcriptomics to recapitulate EHT in vitro and uncover mechanisms by which the haemogenic endothelium generates early haematopoietic cells. We show that most of the endothelial cells reside in a quiescent state and progress to the haematopoietic fate within a defined time window, within which they need to re-enter into the cell cycle. If cell cycle is blocked, haemogenic endothelial cells lose their EHT potential and adopt a non-haemogenic identity. Furthermore, we demonstrate that CDK4/6 and CDK1 play a key role not only in the transition but also in allowing haematopoietic progenitors to establish their full differentiation potential. Conclusion: We propose a direct link between the molecular machineries that control cell cycle progression and EHT.

L’association du vitiligo et du psoriasis a été décrite dès le 19e siècle. Des études épidémiologiques ont montré une association significative entre ces deux pathologies. Cela est également conforté par des nombreux facteurs de prédisposition génétique partagés pathologies, ainsi que des mécanismes physiopathologiques et immunologiques communs, comme le phénomène de Koebner. Cependant il existe peu de données sur l’analyse des caractéristiques démographiques et cliniques de ces pathologies associées chez un même patient.

Le mélanome de Dubreuilh (MD) est une forme de mélanome in situ qui siège dans la grande majorité des cas sur le visage ou le cou, et touche principalement les patients âgés. Bien que d’évolution lente, le MD possède un risque d’invasion du derme puis plus exceptionnellement d’évolution métastatique. Le traitement de référence du MD est la chirurgie, avec le plus faible risque de récidive (2 % pour le Mohs). Cependant, la taille, la localisation et l’âge avancé des patients ne rendent pas toujours la chirurgie réalisable. Parmi les alternatives, la radiothérapie fait partie des techniques décrites comme les plus efficaces (taux de récidive de 10 à 15 %). Cependant, ce chiffre repose sur des études souvent de faible effectif et surtout hétérogènes pour les techniques utilisées : rayons X superficiels (Grenz rays), photons X de basse énergie. À ce jour, aucune série française n’a été publiée sur le sujet.

Variability among pluripotent stem cell (PSC) lines is a prevailing issue that hampers not only experimental reproducibility but also large-scale applications and personalized cell-based therapy. This variability could result from epigenetic and genetic factors that influence stem cell behavior. Naive culture conditions minimize epigenetic fluctuation, potentially overcoming differences in PSC line differentiation potential. Here we derived PSCs from distinct mouse strains under naive conditions and show that lines from distinct genetic backgrounds have divergent differentiation capacity, confirming a major role for genetics in PSC phenotypic variability. This is explained in part through inconsistent activity of extra-cellular signaling, including the Wnt pathway, which is modulated by specific genetic variants. Overall, this study shows that genetic background plays a dominant role in driving phenotypic variability of PSCs.

From 2000 to 2001, nine strains of Salmonella enterica belonging to the new serotype Keurmassar have been isolated from human and poultry samples at the Senegalese National Salmonella and Shigella Reference Laboratory at the Pasteur Institute, in Dakar. All strains carried virulence factors including Salmonella Pathogenicity Islands (SPI)-1, -2, -3 and -5 encoded genes. Strains did not harbour virulence plasmid. Ribotyping analysis revealed a single clone identical to Salmonella Decatur isolated in Zimbabwe. These data suggest that strains are closely related, and may have been spread clonally. In this new serotype, insertion sequence IS200 is not present.

La prévention des effets respiratoires liés aux expositions professionnelles à des aérocontaminants est un enjeu important pour les médecins du travail. Entre 20 et 30 % des bronchites chroniques obstructives (BPCO) sont liées à des expositions professionnelles, comme les particules fines ou ultrafines, qui peuvent induire un stress oxydant. Des biomarqueurs du stress oxydant pourraient être proposés pour le dépistage précoce des effets respiratoires, notamment de la BPCO, à condition d’être validés et mesurables dans des prélèvements biologiques peu invasifs.