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[PMID]: 23223619 [Au] Autor: Borggren M; Navér L; Casper C; Ehrnst A; Jansson M [Ad] Dirección: Department of Laboratory Medicine, Lund University, Lund, Sweden. [Ti] Título: R5 human immunodeficiency virus type 1 with efficient DC-SIGN use is not selected for early after birth in vertically infected children. [So] Fuente: J Gen Virol;94(Pt 4):767-73, 2013 Apr. [Is] ISSN: 1465-2099 [Cp] País de publicación: England [La] Idioma: eng [Ab] Resumen: The binding of human immunodeficiency virus (HIV) to C-type lectin receptors may result in either enhanced trans-infection of T-cells or virus degradation. We have investigated the efficacy of HIV-1 utilization of DC-SIGN, a C-type lectin receptor, in the setting of intrauterine or intrapartum mother-to-child transmission (MTCT). Viruses isolated from HIV-1-infected mothers at delivery and from their vertically infected children both shortly after birth and later during the progression of the disease were analysed for their use of DC-SIGN, binding and ability to trans-infect. DC-SIGN use of a child's earlier virus isolate tended to be reduced as compared with that of the corresponding maternal isolate. Furthermore, the children's later isolate displayed enhanced DC-SIGN utilization compared with that of the corresponding earlier virus. These results were also supported in head-to-head competition assays and suggest that HIV-1 variants displaying efficient DC-SIGN use are not selected for during intrauterine or intrapartum MTCT. However, viruses with increased DC-SIGN use may evolve later in paediatric HIV-1 infections. [Mh] Términos MeSH primario: Moléculas de Adhesión Celular/metabolismo Infecciones por VIH/transmisión Infecciones por VIH/virología VIH-1/patogenicidad Transmisión Vertical de Enfermedad Infecciosa Lectinas Tipo C/metabolismo Complicaciones Infecciosas del Embarazo/virología Receptores de Superficie Celular/metabolismo Acoplamiento Viral [Mh] Términos MeSH secundario: Niño Preescolar Análisis por Conglomerados Femenino Genotipo Humanos Lactante Recién Nacido Masculino Datos de Secuencia Molecular Embarazo ARN Viral/genética Análisis de Secuencia de ADN [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nombre de substancia: 0 (Cell Adhesion Molecules); 0 (DC-specific ICAM-3 grabbing nonintegrin); 0 (Lectins, C-Type); 0 (RNA, Viral); 0 (Receptors, Cell Surface) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 130318 [St] Status: MEDLINE [do] DOI: 10.1099/vir.0.043620-0

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[PMID]: 23269607 [Au] Autor: Jadidi-Niaragh F; Ghalamfarsa G; Memarian A; Asgarian-Omran H; Razavi SM; Sarrafnejad A; Shokri F [Ad] Dirección: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, 14155, Iran. [Ti] Título: Downregulation of IL-17-producing T cells is associated with regulatory T cell expansion and disease progression in chronic lymphocytic leukemia. [So] Fuente: Tumour Biol;34(2):929-40, 2013 Apr. [Is] ISSN: 1423-0380 [Cp] País de publicación: Netherlands [La] Idioma: eng [Ab] Resumen: Little is known about the immunobiology of interleukin-17 (IL-17)-producing T cells and regulatory T cells (Treg) in chronic lymphocytic leukemia (CLL). In this study, the frequencies of Th17, Tc17, and CD39(+) Treg cells were enumerated in peripheral T cells isolated from 40 CLL patients and 15 normal subjects by flow cytometry. Our results showed a lower frequency of Th17 and Tc17 cells in progressive (0.99 ± 0.12 % of total CD3(+)CD4(+) cells; 0.44 ± 0.09 % of total CD8(+) cells) compared to indolent patients (1.57 ± 0.24 %, p = 0.042; 0.82 ± 0.2 %, p = 0.09) and normal subjects (1.78 ± 0.2 %, p = 0.003; 0.71 ± 0.09 %, p = 0.04). Decrease in IL-17-producing T cells was associated with CD39(+) Treg cells expansion. Variation of IL-17-producing cells and Treg cells in indolent and progressive patients was neither associated to the expression levels of Th1- and Th2-specific transcription factors T-bet and GATA-3 nor to the frequencies of IFN-γ and IL-4-producing CD4(+) T cells in a selected number of samples. Additionally, suppressive potential of CD4(+) Treg was similar in CLL patients and normal subjects. Our data indicate that progression of CLL is associated with downregulation of IL-17-producing T cells and expansion of Treg cells, implying contribution of these subsets of T cells in the progression of CLL. [Mh] Términos MeSH primario: Linfocitos T CD4-Positivos/inmunología Linfocitos T CD8-positivos/inmunología Interleucina-17/metabolismo Leucemia Linfocítica Crónica de Células B/metabolismo Linfocitos T Reguladores/inmunología [Mh] Términos MeSH secundario: Adulto Anciano Anciano de 80 o más Años Animales Linfocitos T CD4-Positivos/metabolismo Linfocitos T CD8-positivos/metabolismo Estudios de Casos y Controles Proliferación de la Célula Progresión de la Enfermedad Regulación hacia Abajo Femenino Citometría de Flujo Humanos Interleucina-17/genética Leucemia Linfocítica Crónica de Células B/inmunología Leucemia Linfocítica Crónica de Células B/patología Leucocitos Mononucleares/inmunología Leucocitos Mononucleares/metabolismo Masculino Mediana Edad ARN Mensajero/genética Reacción en Cadena en Tiempo Real de la Polimerasa Reacción en Cadena de la Polimerasa de Transcriptasa Inversa Ovinos Linfocitos T Reguladores/metabolismo Células TH1/inmunología [Pt] Tipo de publicación: COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nombre de substancia: 0 (Interleukin-17); 0 (RNA, Messenger) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 130315 [St] Status: MEDLINE [do] DOI: 10.1007/s13277-012-0628-4

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[PMID]: 23151849 [Au] Autor: Gunderson AJ; Mohammed J; Horvath FJ; Podolsky MA; Anderson CR; Glick AB [Ad] Dirección: Pennsylvania State University, University Park, PA, USA. [Ti] Título: CD8(+) T cells mediate RAS-induced psoriasis-like skin inflammation through IFN-γ. [So] Fuente: J Invest Dermatol;133(4):955-63, 2013 Apr. [Is] ISSN: 1523-1747 [Cp] País de publicación: United States [La] Idioma: eng [Ab] Resumen: The RAS signaling pathway is constitutively activated in psoriatic keratinocytes. We expressed activated H-RAS(V12G) in suprabasal keratinocytes of adult mice and observed rapid development of a psoriasis-like skin phenotype characterized by basal keratinocyte hyperproliferation, acanthosis, hyperkeratosis, intraepidermal neutrophil microabscesses, and increased T helper type 1 (Th1)/Th17 and T cell type 1 (Tc1)/Tc17 skin infiltration. The majority of skin-infiltrating CD8(+) T cells coexpressed IFN-γ and IL-17A. When RAS was expressed on a Rag1-/- background, microabscess formation, inducible nitric oxide synthase expression, and keratinocyte hyperproliferation were suppressed. Depletion of CD8(+), but not CD4(+), T cells reduced cutaneous and systemic inflammation, the RAS-induced increase in cutaneous Th17 and IL-17(+) γδ T cells, and epidermal hyperproliferation to levels similar to a Rag1-/- background. Reconstitution of Rag1-/- inducible RAS mice with purified CD8(+) T cells restored microabscess formation and epidermal hyperproliferation. Neutralization of IFN-γ, but not of IL-17A, in CD8(+) T-cell-reconstituted Rag1-/- mice expressing RAS blocked CD8-mediated skin inflammation, inducible nitric oxide synthase expression, and keratinocyte hyperproliferation. These results show that CD8(+) T cells can orchestrate skin inflammation with psoriasis-like pathology in response to constitutive RAS activation in keratinocytes, and this is primarily mediated through IFN-γ. [Mh] Términos MeSH primario: Linfocitos T CD8-positivos/patología Interferón gamma/inmunología Proteínas Proto-Oncogénicas p21(ras)/inmunología Psoriasis/inmunología Psoriasis/patología Transducción de Señal/inmunología [Mh] Términos MeSH secundario: Absceso/inmunología Absceso/patología Animales Linfocitos T CD8-positivos/inmunología Proliferación de la Célula Dermatitis/genética Dermatitis/inmunología Dermatitis/patología Epidermis/inmunología Epidermis/metabolismo Epidermis/patología Femenino Interferón gamma/metabolismo Interleucina-17/genética Interleucina-17/inmunología Interleucina-17/metabolismo Queratinocitos/inmunología Queratinocitos/metabolismo Queratinocitos/patología Masculino Ratones Ratones Transgénicos Neutrófilos/inmunología Neutrófilos/patología Fenotipo Proteínas Proto-Oncogénicas p21(ras)/genética Proteínas Proto-Oncogénicas p21(ras)/metabolismo Psoriasis/genética Células TH1/inmunología Células TH1/patología Células Th17/inmunología Células Th17/patología [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nombre de substancia: 0 (Il17a protein, mouse); 0 (Interleukin-17); 82115-62-6 (Interferon-gamma); EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 130314 [St] Status: MEDLINE [do] DOI: 10.1038/jid.2012.390

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[PMID]: 23305733 [Au] Autor: Geng S; Matsushima H; Okamoto T; Yao Y; Lu R; Page K; Blumenthal RM; Ward NL; Miyazaki T; Takashima A [Ad] Dirección: Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, OH 43614, USA. [Ti] Título: Emergence, origin, and function of neutrophil-dendritic cell hybrids in experimentally induced inflammatory lesions in mice. [So] Fuente: Blood;121(10):1690-700, 2013 Mar 7. [Is] ISSN: 1528-0020 [Cp] País de publicación: United States [La] Idioma: eng [Ab] Resumen: Although unusual neutrophils expressing major histocompatibility complex class II (MHC II) and costimulatory molecules have been detected at inflammatory sites in mice and humans, their identity, origin, and function remain unclear. We have demonstrated that, when cultured with granulocyte macrophage-colony-stimulating factor, neutrophils can give rise to a unique hybrid population exhibiting dual phenotypic and functionality of neutrophils and dendritic cells (DCs). Here we report that hybrid cells expressing surface markers of neutrophils (Ly6G, L-selectin, CXC chemokines receptor 2, and 7/4) and DCs (CD11c, MHC II, CD80, and CD86) become detectable in the peritoneal cavity, skin, lung, and lymph nodes under inflammatory conditions. Importantly, 20% to 30% of the adoptively transferred neutrophils acquired CD11c and MHC II expression when recovered from inflammatory lesions, demonstrating neutrophil → hybrid conversion in living animals. Using Escherichia coli strains expressing green fluorescent protein and ovalbumin, we further show hybrids play dual protective roles by rapidly clearing bacteria and presenting bacterial antigens to CD4 T cells. These results indicate that some of the neutrophils recruited to inflammatory lesions can differentiate into neutrophil-DC hybrids, thus challenging the classic view of neutrophils as terminally differentiated leukocytes destined to die or to participate primarily in host innate immunity. [Mh] Términos MeSH primario: Células Dendríticas/fisiología Modelos Animales de Enfermedad Escherichia coli/patogenicidad Células Híbridas/fisiología Inflamación/inmunología Neutrófilos/fisiología Peritonitis/etiología [Mh] Términos MeSH secundario: Animales Presentación de Antígeno Células Presentadoras de Antígenos/inmunología Marcadores Biológicos/metabolismo Western Blotting Diferenciación Celular Células Cultivadas Citocinas/inmunología Citocinas/metabolismo Células Dendríticas/citología Células Dendríticas/microbiología Infecciones por Escherichia coli/inmunología Infecciones por Escherichia coli/microbiología Infecciones por Escherichia coli/patología Citometría de Flujo Proteinas Fluorescentes Verdes/metabolismo Antígenos de Histocompatibilidad Clase II/metabolismo Células Híbridas/citología Células Híbridas/microbiología Inmunofenotipificación Inflamación/microbiología Inflamación/patología Pulmón/inmunología Pulmón/microbiología Pulmón/patología Ratones Ratones Consanguíneos C57BL Ratones Noqueados Neutrófilos/citología Neutrófilos/microbiología Peritonitis/metabolismo Peritonitis/patología Piel/inmunología Piel/microbiología Piel/patología [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nombre de substancia: 0 (Biological Markers); 0 (Cytokines); 0 (Histocompatibility Antigens Class II); 0 (enhanced green fluorescent protein); 147336-22-9 (Green Fluorescent Proteins) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: AIM; IM [Da] Fecha de ingreso para procesamiento: 130308 [St] Status: MEDLINE [do] DOI: 10.1182/blood-2012-07-445197

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[PMID]: 23305731 [Au] Autor: Matsushima H; Geng S; Lu R; Okamoto T; Yao Y; Mayuzumi N; Kotol PF; Chojnacki BJ; Miyazaki T; Gallo RL; Takashima A [Ad] Dirección: Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, OH 43614, USA. [Ti] Título: Neutrophil differentiation into a unique hybrid population exhibiting dual phenotype and functionality of neutrophils and dendritic cells. [So] Fuente: Blood;121(10):1677-89, 2013 Mar 7. [Is] ISSN: 1528-0020 [Cp] País de publicación: United States [La] Idioma: eng [Ab] Resumen: Neutrophils have been reported to acquire surface expression of MHC class II and co-stimulatory molecules as well as T-cell stimulatory activities when cultured with selected cytokines. However, cellular identity of those unusual neutrophils showing antigen presenting cell (APC)-like features still remains elusive. Here we show that both immature and mature neutrophils purified from mouse bone marrow differentiate into a previously unrecognized "hybrid" population showing dual properties of both neutrophils and dendritic cells (DCs) when cultured with granulocyte macrophage-colony-stimulating factor but not with other tested growth factors. The resulting hybrid cells express markers of both neutrophils (Ly6G, CXCR2, and 7/4) and DCs (CD11c, MHC II, CD80, and CD86). They also exhibit several properties typically reserved for DCs, including dendritic morphology, probing motion, podosome formation, production of interleukin-12 and other cytokines, and presentation of various forms of foreign protein antigens to naïve CD4 T cells. Importantly, they retain intrinsic abilities of neutrophils to capture exogenous material, extrude neutrophil extracellular traps, and kill bacteria via cathelicidin production. Not only do our results reinforce the notion that neutrophils can acquire APC-like properties, they also unveil a unique differentiation pathway of neutrophils into neutrophil-DC hybrids that can participate in both innate and adaptive immune responses. [Mh] Términos MeSH primario: Células Presentadoras de Antígenos/inmunología Diferenciación Celular Citocinas/inmunología Células Dendríticas/citología Células Híbridas/citología Neutrófilos/citología [Mh] Términos MeSH secundario: Animales Presentación de Antígeno Marcadores Biológicos/metabolismo Western Blotting Células Cultivadas Citocinas/metabolismo Células Dendríticas/fisiología Citometría de Flujo Perfilación de la Expresión Génica Células Híbridas/fisiología Ratones Ratones Consanguíneos C57BL Ratones Noqueados Neutrófilos/fisiología Análisis de Secuencia en Orden de Oligonucleótido Fagocitosis Fenotipo [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nombre de substancia: 0 (Biological Markers); 0 (Cytokines) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: AIM; IM [Da] Fecha de ingreso para procesamiento: 130308 [St] Status: MEDLINE [do] DOI: 10.1182/blood-2012-07-445189

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[PMID]: 23070224 [Au] Autor: Liu Y; Liu S; Su X [Ad] Dirección: Department of Orthopedic Surgery, The PLA 307th Hospital, No.8, Fengtaidongda Road, Beijing 100071, People's Republic of China. [Ti] Título: Core decompression and implantation of bone marrow mononuclear cells with porous hydroxylapatite composite filler for the treatment of osteonecrosis of the femoral head. [So] Fuente: Arch Orthop Trauma Surg;133(1):125-33, 2013 Jan. [Is] ISSN: 1434-3916 [Cp] País de publicación: Germany [La] Idioma: eng [Ab] Resumen: BACKGROUND: Implanted bone marrow mononuclear cells (BMMCs) may promote both osteogenesis and angiogenesis in the femoral head. The aim of this study was to investigate the effectiveness of core decompression and implantation of BMMCs with porous hydroxyapatite bone filler for the treatment of osteonecrosis of the femoral head (ONFH). METHODS: Patients with ONFH underwent core decompression and implantation of nano-hydroxyapatite/polyamide bone filler with or without BMMCs. Primary outcomes were changes in Harris hip and visual analogue scale (VAS) pain scores. Secondary outcomes included radiological and clinical success rates, adverse events, and complications. RESULTS: Demographic/baseline characteristics were similar between groups (BMMC, n = 17 with 26 ONFH hips; control, n = 17 with 27 ONFH hips). Harris hip scores were significantly increased (P < 0.05) in both groups of patients after surgery (last follow-up). The magnitude of increase was significantly greater in the BMMC as compared with the control group (28.6 ± 0.5 vs. 18.4 ± 1.7 %, P < 0.001). VAS scores were significantly decreased (P < 0.05) in both groups after surgery (last follow-up). The magnitude of decrease was significantly greater in the BMMC as compared with the control group (-66.3 ± 1.4 vs. -51.7 ± 2.9 %, P < 0.001). Radiological and clinical success rates were significantly higher in the BMMC as compared with the control group (82.5 vs. 40.7 % and 75.4 vs. 37.0 %, respectively, P < 0.001). Postoperative collapse of the femoral head was less common in the BMMC as compared with the control group (17.5 vs. 59.3 %, P < 0.01). CONCLUSIONS: Both core decompression with or without implantation of BMMC are effective treatment for ONFH. However, core decompression with implantation of BMMCs and porous hydroxyapatite bone filler may be a more effective treatment for ONFH. [Mh] Términos MeSH primario: Necrosis de la Cabeza Femoral/cirugía Leucocitos Mononucleares/trasplante [Mh] Términos MeSH secundario: Adulto Materiales Biocompatibles Trasplante de Médula Ósea Descompresión Quirúrgica Durapatita/administración & dosificación Femenino Humanos Masculino Mediana Edad Estudios Retrospectivos [Pt] Tipo de publicación: JOURNAL ARTICLE [Nm] Nombre de substancia: 0 (Biocompatible Materials); 1306-06-5 (Durapatite) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 130103 [St] Status: MEDLINE [do] DOI: 10.1007/s00402-012-1623-3

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[PMID]: 23182461 [Au] Autor: Mougel F; Bonnefoy F; Kury-Paulin S; Borot S; Perruche S; Kantelip B; Penfornis A; Saas P; Kleinclauss F [Ad] Dirección: Inserm, UMR1098, 25020 Besançon, France. francoismougel@gmail.com [Ti] Título: Intravenous infusion of donor apoptotic leukocytes before transplantation delays allogeneic islet graft rejection through regulatory T cells. [So] Fuente: Diabetes Metab;38(6):531-7, 2012 Dec. [Is] ISSN: 1878-1780 [Cp] País de publicación: France [La] Idioma: eng [Ab] Resumen: AIM: This study describes the ability of intravenous donor apoptotic leukocyte infusion before islet transplantation to delay allogeneic graft rejection and implicates regulatory T cells (T(reg)) in the effect. METHODS: Allogeneic FVB (Friend virus B-type) islet transplants were placed under the kidney capsule of BALB/c recipient mice rendered diabetic by streptozotocin. Apoptotic donor leukocytes were infused intravenously 7 days before transplantation. Foxp3/DTR/GFP transgenic C57BL/6 mice were used as recipients to show depletion of T(reg) after apoptotic cell infusion. Control mice received islet transplants without apoptotic cells. RESULTS: The graft median survival time (MST) in recipient mice was 15±1.5 days when apoptotic cells were infused 7 days prior to transplantation of a 1000-islet-containing allograft and 6±0.5 days in the control mice (P<0.01). The same effect was observed using a 500-islet allograft, with an MST of 9±1.1 days vs. 3±0.8 days with and without (controls) apoptotic cells, respectively (P<0.01). This immunomodulatory effect was not observed when apoptotic cell administration was performed on the day of transplantation. Specific T(reg) depletion in Foxp3/DTR/GFP recipient mice inhibited the beneficial effect of apoptotic cell infusion with an MST of 8±1.5 days after apoptotic cell infusion vs. 2±0.2 days when T(reg) were depleted (P<0.01). Furthermore, T(reg) were specifically detected in the islet grafts of mice infused with apoptotic cells prior to islet transplantation. CONCLUSION: Infusion of donor apoptotic cells 7 days before allogeneic transplantation delays islet allograft rejection through a process involving T(reg). [Mh] Términos MeSH primario: Apoptosis/inmunología Rechazo de Injerto/prevención & control Trasplante de Islotes Pancreáticos/métodos Transfusión de Leucocitos/métodos Linfocitos T Reguladores/inmunología [Mh] Términos MeSH secundario: Animales Diabetes Mellitus Experimental/cirugía Femenino Rechazo de Injerto/inmunología Inmunomodulación Leucocitos/citología Leucocitos/inmunología Ratones Ratones Consanguíneos BALB C [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 121210 [St] Status: MEDLINE

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[PMID]: 23107224 [Au] Autor: Himmelsbach K; Hildt E [Ad] Dirección: Paul-Ehrlich-Institute, Division of Virology, Langen, Germany. [Ti] Título: The kinase inhibitor Sorafenib impairs the antiviral effect of interferon α on hepatitis C virus replication. [So] Fuente: Eur J Cell Biol;92(1):12-20, 2013 Jan. [Is] ISSN: 1618-1298 [Cp] País de publicación: Germany [La] Idioma: eng [Ab] Resumen: Recently, it was shown that the kinase inhibitor Sorafenib efficiently blocks HCV replication by inhibition of c-Raf. However, a longer treatment with higher doses of Sorafenib might be associated with adverse effects. Therefore, it was analysed whether a decreased dose of Sorafenib can be applied in combination with interferon α to obtain additive antiviral, but at the same time decreased adverse effects. However, Sorafenib abolishes the inhibitory effect of interferon α on HCV replication and vice versa. In order to reveal the underlying mechanisms, we observed that on the one hand IFNα activates c-Raf and thereby counteracts the inhibitory effect of Sorafenib on HCV replication that is based on the Sorafenib-dependent inhibition of c-Raf. On the other hand we found that the IFNα-induced PKR-phosphorylation depends on c-Raf. So, Sorafenib as a potent inhibitor of c-Raf prevents the IFNα-dependent PKR phosphorylation. Moreover, Sorafenib inhibits c-Raf-independent the phosphorylation of STAT1 resulting in an impaired induction of IFNα-dependent genes. Taken together, these data indicate that a combined application of Sorafenib and interferon α in order to obtain an antiviral effect is not useful since Sorafenib exerts an inhibitory effect on targets that are crucial for the transduction of interferon α-dependent antiviral response. [Mh] Términos MeSH primario: Antivirales/antagonistas & inhibidores Hepacivirus/fisiología Interferón alfa/antagonistas & inhibidores Niacinamida/análogos & derivados Compuestos de Fenilurea/farmacología Inhibidores de las Proteína Quinasas/farmacología Replicación Viral/efectos de drogas [Mh] Términos MeSH secundario: Línea Celular Tumoral Humanos Niacinamida/farmacología Fosforilación Proteínas Proto-Oncogénicas c-raf/antagonistas & inhibidores [Pt] Tipo de publicación: JOURNAL ARTICLE [Nm] Nombre de substancia: 0 (Antiviral Agents); 0 (Interferon-alpha); 0 (Phenylurea Compounds); 0 (Protein Kinase Inhibitors); 0 (sorafenib); 98-92-0 (Niacinamide); EC 2.7.11.1 (Proto-Oncogene Proteins c-raf) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 121203 [St] Status: MEDLINE

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[PMID]: 22991336 [Au] Autor: Libbey JE; Tsunoda I; Fujinami RS [Ad] Dirección: Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. [Ti] Título: Possible role of interleukin-17 in a prime/challenge model of multiple sclerosis. [So] Fuente: J Neurovirol;18(6):471-8, 2012 Dec. [Is] ISSN: 1538-2443 [Cp] País de publicación: United States [La] Idioma: eng [Ab] Resumen: No one single pathogen has been identified as the causative agent of multiple sclerosis (MS). Alternately, the likelihood of an autoimmune event may be nonspecifically enhanced by different infectious agents. In a novel animal model of MS, SJL/J mice primed through infection with a recombinant vaccinia virus (VV) encoding myelin proteolipid protein (PLP) (VV(PLP)) were susceptible to a central nervous system (CNS) inflammatory disease following administration of a nonspecific immunostimulant [complete Freund's adjuvant (CFA) plus Bordetella pertussis (BP)]. Mononuclear cells isolated from the brains, but not the spleens, of VV(PLP)-primed CFA/BP challenged mice produced interleukin (IL)-17 and interferon-γ and transferred a CNS inflammatory disease to naïve SJL/J mice. Administration of curdlan, a T helper 17 cell inducer, unexpectedly resulted in less severe clinical and histological signs of disease, compared to CFA/BP challenged mice, despite the induction of IL-17 in the periphery. Further examination of the VV(PLP)-prime CFA/BP challenge model may suggest new mechanisms for how different pathogens associated with MS can protect or enhance disease. [Mh] Términos MeSH primario: Encéfalo/inmunología Interleucina-17/inmunología Leucocitos Mononucleares/inmunología Esclerosis Múltiple/inmunología [Mh] Términos MeSH secundario: Adyuvantes Inmunológicos/administración & dosificación Animales Encéfalo/metabolismo Encéfalo/patología Modelos Animales de Enfermedad Femenino Vectores Genéticos Inmunomodulación Interferón gamma/biosíntesis Interferón gamma/inmunología Interleucina-17/biosíntesis Leucocitos Mononucleares/metabolismo Leucocitos Mononucleares/patología Leucocitos Mononucleares/trasplante Ratones Esclerosis Múltiple/metabolismo Esclerosis Múltiple/patología Proteína Proteolipídica de la Mielina/genética Proteína Proteolipídica de la Mielina/inmunología Especificidad de Órganos Polisacáridos Bacterianos/administración & dosificación Ratas Proteínas Recombinantes/genética Proteínas Recombinantes/inmunología Índice de Severidad de la Enfermedad Bazo/inmunología Bazo/metabolismo Bazo/patología Virus Vaccinia/genética beta-Glucanos/administración & dosificación [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL [Nm] Nombre de substancia: 0 (Adjuvants, Immunologic); 0 (Interleukin-17); 0 (Myelin Proteolipid Protein); 0 (Polysaccharides, Bacterial); 0 (Recombinant Proteins); 0 (beta-Glucans); 54724-00-4 (curdlan); 82115-62-6 (Interferon-gamma) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 121127 [St] Status: MEDLINE [do] DOI: 10.1007/s13365-012-0125-y

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[PMID]: 22722448 [Au] Autor: Liu G; Yang W; Guo M; Liu X; Huang N; Li D; Jiang Z; Yang W; Zhang W; Su H; Liu Z; Liu T; Wang D; Huang S; Yao B; Man Q; Qiu L; Sun X; Sun Y; Liu B [Ad] Dirección: Department of Hematology and Transplantation, Affiliated Hospital of the Academy of Military Medical Sciences, Dongdajie 8, Beijing, 100071, China. liugx270@hotmail.com [Ti] Título: Effective modulation of CD4(+)CD25 (+high) regulatory T and NK cells in malignant patients by combination of interferon-α and interleukin-2. [So] Fuente: Cancer Immunol Immunother;61(12):2357-66, 2012 Dec. [Is] ISSN: 1432-0851 [Cp] País de publicación: Germany [La] Idioma: eng [Ab] Resumen: Overinduced CD4(+)CD25(+high) regulatory T cells (Treg) and downregulated NK cells contribute to tumor-relevant immune tolerance and interfere with tumor immunity. In this study, we aimed to design a novel strategy with cytokine combination to correct the dysregulated Treg and NK cells in malignant patients. Initially, a total of 58 healthy individuals and 561 malignant patients were analyzed for their cellular immunity by flow cytometry. The average percentages of CD4(+)CD25(+high)/lymphocyte were 1.30 ± 1.19 % ([Formula: see text] ± SD) in normal adults and 3.274 ± 4.835 % in malignant patients (p < 0.001). The ratio of CD4(+)CD25(+high) to CD4(+) was 3.58 ± 3.19 % in normal adults and 6.01 ± 5.89 % to 13.50 ± 23.60 % in different kinds of malignancies (p < 0.001). Of normal adults, 15.52 % had >3 % Treg and 12.07 % had <10 % NK cells. In contrast, the Treg (>3 %) and NK (<10 %) percentages were 40.82 and 34.94 % in malignant patients, respectively. One hundred and ten patients received the immunomodulation therapy with IFN-α and/or IL-2. The overinduced Treg in 86.3 % and the reduced NK cells in 71.17 % of the patients were successfully modulated. In comparison, other lymphocyte subpopulations in most patients were much less affected by this treatment. No other treatment-relevant complications except slight pyrexia, fatigue, headache, and myalgia were observed. In conclusion, dysregulated Treg and/or NK cells were common in malignant patients. Different from any regimens ever reported, this strategy was simple and effective without severe complications and will become a basic regimen for other cancer therapies. [Mh] Términos MeSH primario: Linfocitos T CD4-Positivos/inmunología Interferón alfa/uso terapéutico Subunidad alfa del Receptor de Interleucina-2/inmunología Interleucina-2/uso terapéutico Células Asesinas Naturales/inmunología Neoplasias/inmunología Linfocitos T Reguladores/inmunología [Mh] Términos MeSH secundario: Adulto Anciano Femenino Humanos Inmunidad Celular/inmunología Inmunomodulación/inmunología Interferón alfa/inmunología Interleucina-2/inmunología Masculino Mediana Edad Neoplasias/terapia [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nombre de substancia: 0 (IL2RA protein, human); 0 (Interferon-alpha); 0 (Interleukin-2); 0 (Interleukin-2 Receptor alpha Subunit) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 121127 [St] Status: MEDLINE [do] DOI: 10.1007/s00262-012-1297-2

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