223 research outputs found
Differential impact of L-arginine deprivation on the activation and effector functions of T cells and macrophages.
No full textThe metabolism of the amino acid L-arginine is emerging as a crucial mechanism for the regulation of immune responses. Here, we characterized the impact of L-arginine deprivation on T cell and macrophage (MPhi) effector functions: We show that whereas L-arginine is required unconditionally for T cell activation, MPhi can up-regulate activation markers and produce cytokines and chemokines in the absence of L-arginine. Furthermore, we show that L-arginine deprivation does not affect the capacity of activated MPhi to up-regulate L-arginine-metabolizing enzymes such as inducible NO synthase and arginase 1. Thus, our results show that to exert their effector functions, T cells and MPhi have different requirements for L-arginine
Fourth-line rescue therapy with rifabutin in patients with three Helicobacter pylori eradication failures
No full textGisbert, J.P., Castro-Fernandez, M., Perez-Aisa, A., Cosme, A., Molina-Infante, J., Rodrigo, L., Modolell, I., Cabriada, J.L., Gisbert, J.L., Lamas, E., Marcos, E., Calvet, X
Development and validation of confocal endomicroscopy diagnostic criteria for low-grade dysplasia in Barrett’s esophagus
No full textBackground: Low-grade dysplasia (LGD) in Barrett’s esophagus (BE) is generally inconspicuous on conventional and magnified endoscopy. Probe-based confocal laser endomicroscopy (pCLE) provides insight into gastro-intestinal mucosa at cellular resolution. We aimed to identify endomicroscopic features and develop pCLE diagnostic criteria for BE-related LGD.Methods: This was a retrospective study on pCLE videos generated in two prospective studies. In Phase I, two investigators assessed 30 videos to identify LGD endomicroscopic features, which were then validated in an independent video set (n=25). Criteria with average accuracy >80% and interobserver agreement κ>0.4 were taken forward. In Phase II, 6 endoscopists evaluated the criteria in an independent video set (n=37). The area under receiver operating characteristic (AROC) curve was constructed to find the best cut-off. Sensitivity, specificity, interobserver and intraobserver agreement were calculated. Results: In Phase I 6 out of 8 criteria achieved the agreement and accuracy thresholds (i. dark non-round glands, ii. irregular gland shape, iii. lack of goblet cells, iv. sharp cut-off of darkness, v. variable cell size and vi. cellular stratification). The best cut-off for LGD diagnosis was 3 out of 6 positive criteria. In Phase II, the diagnostic criteria had a sensitivity and specificity for LGD of 81.69% and 6774.6%, respectively, with an AROC of 0.860888. The interobserver agreement was substantial (κ= 0.631654) and the mean intraobserver agreement was moderate (κ= 0.590). Conclusions: We have generated and validated pCLE criteria for LGD in BE. Using these criteria, pCLE diagnosis of LGD is reproducible and has substantial interobserver agreement
Antiparasitic activities and toxicities of individual enantiomers of the 8-aminoquinoline 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3,4-dichloropheno xy]quinoline succinate
No full text8-Aminoquinolines are an important class of antiparasitic agents, with broad utility and excellent efficacy, but also limitations due to hematological toxicities, primarily methemoglobinemia and hemolysis. One representative from this class, (+/-) -8- [(4-amino-1-methylbutyl)amino] -6-methoxy-4-methyl-5- [3,4-dichlorophenoxy]quinoline succinate (NPC1161C), proved extremely efficacious in animal models of malaria and pneumocystis pneumonia. This racemic mixture was separated into its component enantiomers by chemical and chromatographic means. The enantiomers were evaluated for antiparasitic activity in murine models of Plasmodium berghei, Pneumocystis carinii, and Leishmania donovani infection, as well as the propensity to elicit hematotoxicity in dogs. The (-)-enantiomer NPC1161B was found to be more active (by severalfold, depending on the dosing regimen) than the (+)-enantiomer NPC1161A in all of these murine models. In addition, the (-) enantiomer showed markedly reduced general toxicity in mice and reduced hematotoxicity in the dog model of methemoglobinemia. It is concluded that the configuration at the asymmetric center in the 8-amino side chain differentially affects efficacy and toxicity profiles and thus may be an important determinant of the "therapeutic window" for compounds in this class
Local increase of arginase activity in lesions of patients with cutaneous leishmaniasis in Ethiopia.
No full textBACKGROUND: Cutaneous leishmaniasis is a vector-borne disease that is in Ethiopia mainly caused by the parasite Leishmania aethiopica. This neglected tropical disease is common in rural areas and causes serious morbidity. Persistent nonhealing cutaneous leishmaniasis has been associated with poor T cell mediated responses; however, the underlying mechanisms are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We have recently shown in an experimental model of cutaneous leishmaniasis that arginase-induced L-arginine metabolism suppresses antigen-specific T cell responses at the site of pathology, but not in the periphery. To test whether these results translate to human disease, we recruited patients presenting with localized lesions of cutaneous leishmaniasis and assessed the levels of arginase activity in cells isolated from peripheral blood and from skin biopsies. Arginase activity was similar in peripheral blood mononuclear cells (PBMCs) from patients and healthy controls. In sharp contrast, arginase activity was significantly increased in lesion biopsies of patients with localized cutaneous leishmaniasis as compared with controls. Furthermore, we found that the expression levels of CD3ζ, CD4 and CD8 molecules were considerably lower at the site of pathology as compared to those observed in paired PBMCs. CONCLUSION: Our results suggest that increased arginase in lesions of patients with cutaneous leishmaniasis might play a role in the pathogenesis of the disease by impairing T cell effector functions
IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype
No full textBackground"Alternatively-activated" macrophages are found in Th2-mediated inflammatory settings such as nematode infection and allergic pulmonary inflammation. Due in part to a lack of markers, these cells have not been well characterized in vivo and their function remains unknown.ResultsWe have used murine macrophages elicited by nematode infection (NeMφ) as a source of in vivo derived alternatively activated macrophages. Using three distinct yet complementary molecular approaches we have established a gene expression profile of alternatively activated macrophages and identified macrophage genes that are regulated in vivo by IL-4. First, genes abundantly expressed were identified by an expressed sequence tag strategy. Second, an array of 1176 known mouse genes was screened for differential expression between NeMφ from wild type or IL-4 deficient mice. Third, a subtractive library was screened to identify novel IL-4 dependent macrophage genes. Differential expression was confirmed by real time RT-PCR analysis.ConclusionsOur data demonstrate that alternatively activated macrophages generated in vivo have a gene expression profile distinct from any macrophage population described to date. Several of the genes we identified, including those most abundantly expressed, have not previously been associated with macrophages and thus this study provides unique new information regarding the phenotype of macrophages found in Th2-mediated, chronic inflammatory settings. Our data also provide additional in vivo evidence for parallels between the inflammatory processes involved in nematode infection and allergy
The reception of Karl Löwith’s Philosophy
No full textEn aquest article es repassen les recepcions que s’han fet del pensament de Karl Löwith. En elles es veu que el pensament de l’autor alemany va ser rebut amb diferents accents, entre els quals hi eren presents des dels prejudicis més evidents fins a la crítica més sincera i oberta d’aquest filòsof, que sobten per la seva gran distància entre elles, que sovint s’allunyen del context i de la situació personal de l’autor que considerem.
Paraules clau: Karl Löwtih, filosofia alemanya, escepticismeIn this study we are trying to oversee the different ways Karl Löwith’s philosophical ideas have been received. In fact, they have been read very differently: with a lot of biased opinions and with objective and open critique altogether. The reviews are far away one from the other, in such a way that may surprise the reader. Really very often they do not take the personal and the cultural environment of the german thinker ino account.
Key words: Karl Löwith, German Philosophy, Scepticis
Especificación del borde notum-axila dorsal en Drosophila melanogaster Función de los genes msh e iroquois
No full textTesis doctoral inédita leída en la Universidad Autónoma de Madrid. Dpto de Biología molecular. Fecha de lectura 22-10-200
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