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a-Interferon therapy for HBV-related glomerulonephritis

Lopes Neto,Edmundo Pessoa de Almeida; Lopes,Lucila Valente; Kirsztajn,Gianna Mastroianni; Cruz,Cibele Nascimento; Ferraz,Maria Lucia Gomes; Silva,Antonio Eduardo Benedito
Fonte: Associação Paulista de Medicina - APM Publicador: Associação Paulista de Medicina - APM
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/1998 Português
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We report a case of a patient with hepatitis B virus (HBV)-related membranous glomerulonephritis (MGN) who showed improvement after interferon-a (IFN-a) therapy. A 35-year-old man with nephrotic syndrome and HBV antigens received a 24-week course of IFN-a. At the end of therapy there was an elevation in the level of plasma aminotransferase and an increase in proteinuria, which were followed by antigen/antibody seroconversion. This "flare-up" before seroconversion suggests an increase in disease activity in the liver and kidney, demonstrating in vivo HBV involvement in MGN.

Transcription of interferon stimulated genes in response to porcine rubulavirus infection in vitro

Flores-Ocelotl,María del Rosario; Rosas-Murrieta,Nora Hilda; Vallejo-Ruiz,Verónica; Reyes-Leyva,Julio; Herrera-Camacho,Irma; Santos-López,Gerardo
Fonte: Sociedade Brasileira de Microbiologia Publicador: Sociedade Brasileira de Microbiologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2011 Português
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Porcine rubulavirus (PoRV) is an emerging virus causing meningo-encephalitis and reproductive failures in pigs. Little is known about the pathogenesis and immune evasion of this virus; therefore research on the mechanisms underlying tissue damage during infection is essential. To explore these mechanisms, the effect of PoRV on the transcription of interferon (IFN) pathway members was analyzed in vitro by semi-quantitative RT-PCR. Ten TCID50 of PoRV stimulated transcription of IFNα, IFNβ, STAT1, STAT2, p48 and OAS genes in neuroblastoma cells, whereas infection with 100 TCID50 did not stimulate transcription levels more than non-infected cells. When the cells were primed with IFNα, infection with 1 TCDI50 of PoRV sufficed to stimulate the transcription of the same genes, but 10 and 100 TCID50 did not modify the transcription level of those genes as compared with non-infected and primed controls. MxA gene transcription was observed only when the cells were primed with IFNα and stimulated with 10 TCID50, whereas 100 TCID50 of PoRV did not modify the MxA transcription level as compared to non-infected and primed cells. Our results show that PoRV replication at low titers stimulates the expression of IFN-responsive genes in neuroblastoma cells...

Poly-ε-caprolactone microspheres containing interferon alpha as alternative formulations for the treatment of chronic hepatitis C

Melo,Cristiane da Silva; Pereira,Bruno Gonçalves; Silva-Cunha,Armando; Fialho,Sílvia Ligório
Fonte: Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Publicador: Universidade de São Paulo, Faculdade de Ciências Farmacêuticas
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2012 Português
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Interferon-alpha (IFN-alpha) is one of the main drugs used in the treatment of hepatitis C. Use of IFN-alpha has some limitations that result in poor treatment efficacy and low patient compliance. Therefore, the aim of this study was to develop poly-ε-caprolactone (PCL) microspheres containing IFN-alpha as an alternative for the treatment of chronic hepatitis C. Microspheres were prepared using the multiple emulsion followed by solvent evaporation technique. Particle size, surface morphology, drug content and encapsulation efficiency of the microspheres produced were evaluated. The stability of the formulation was assessed after 90 days at -20ºC. An in vitro release study was performed in PBS. In vitro cytotoxicity of the formulation was studied using hepatic cell line. The freeze-dried microspheres had mean particle size, IFN-alpha content, and encapsulation efficiency of 38.52 ± 4.64 µm, 15.52 ± 3.28% and 83.93 ± 5.76%, respectively. There were no significant changes during storage and the structural integrity of the protein was not compromised by the preparation technique. A total of 82% of the IFN-alpha was released after 28 days and the developed microspheres did not present cytotoxicity to the hepatic cell line. In vivo studies are currently underway to evaluate the biological activity of IFN-alpha encapsulated into microspheres.

Interferon-Lambda: A New Addition to an Old Family

Donnelly, Raymond P.; Kotenko, Sergei V.
Fonte: Mary Ann Liebert, Inc. Publicador: Mary Ann Liebert, Inc.
Tipo: Artigo de Revista Científica
Publicado em /08/2010 Português
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The discovery and initial description of the interferon-λ (IFN-λ) family in early 2003 opened an exciting new chapter in the field of IFN research. There are 3 IFN-λ genes that encode 3 distinct but highly related proteins denoted IFN-λ1, -λ2, and -λ3. These proteins are also known as interleukin-29 (IL-29), IL-28A, and IL-28B, respectively. Collectively, these 3 cytokines comprise the type III subset of IFNs. They are distinct from both type I and type II IFNs for a number of reasons, including the fact that they signal through a heterodimeric receptor complex that is different from the receptors used by type I or type II IFNs. Although type I IFNs (IFN-α/β) and type III IFNs (IFN-λ) signal via distinct receptor complexes, they activate the same intracellular signaling pathway and many of the same biological activities, including antiviral activity, in a wide variety of target cells. Consistent with their antiviral activity, expression of the IFN-λ genes and their corresponding proteins is inducible by infection with many types of viruses. Therefore, expression of the type III IFNs (IFN-λs) and their primary biological activity are very similar to the type I IFNs. However, unlike IFN-α receptors which are broadly expressed on most cell types...

Interferon beta 1b following natalizumab discontinuation: one year, randomized, prospective, pilot trial

Gobbi, Claudio; Meier, Dominik S; Cotton, François; Sintzel, Martina; Leppert, David; Guttmann, Charles R G; Zecca, Chiara
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Português
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Background: Natalizumab (NTZ) discontinuation leads to multiple sclerosis reactivation. The objective of this study is to compare disease activity in MS patients who continued on NTZ treatment to those who were switched to subcutaneous interferon 1b (IFNB) treatment. Methods: 1-year randomized, rater-blinded, parallel-group, pilot study (ClinicalTrial.gov ID: NCT01144052). Relapsing remitting MS patients on NTZ for ≥12 months who had been free of disease activity on this therapy (no relapses and disability progression for ≥6 months, no gadolinium-enhancing lesions on baseline MRI) were randomized to NTZ or IFNB. Primary endpoint was time to first on-study relapse. Additional clinical, MRI and safety parameters were assessed. Analysis was based on intention to treat. Results: 19 patients (NTZ n=10; IFNB n=9) with similar baseline characteristics were included. 78% of IFNB treated patients remained relapse free (NTZ group: 100%), and 25% remained free of new T2 lesions (NTZ group: 62.5%). While time to first on-study relapse was not significantly different between groups (p=0.125), many secondary clinical and radiological endpoints (number of relapses, proportion of relapse free patients, number of new T2 lesions) showed a trend...

Treatment satisfaction, adherence and behavioral assessment in patients de – escalating from natalizumab to interferon beta

Zecca, Chiara; Riccitelli, Gianna C; Calabrese, Pasquale; Pravatà, Emanuele; Candrian, Ursula; Guttmann, Charles RG; Gobbi, Claudio
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Português
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Background: De-escalating natalizumab (NTZ) to interferon beta 1b (IFN B 1B) is a possible treatment option in multiple sclerosis (MS) patients interrupting NTZ because of increased risk of progressive multifocal leukoencephalopathy (PML). The aim of this study was to evaluate satisfaction and adherence to treatment, behavioral and fatigue changes in patients switched to IFN B 1B compared to continued NTZ treatment. Methods: A 1 year, prospective, randomized, rater-blinded, parallel-group study. Nineteen relapsing remitting (RR) MS patients, randomly assigned to undergo either NTZ (n = 10) or IFN B 1B (n = 9) treatment, who had previously received NTZ for at least 12 months with disease stability and fearing or at risk for PML were included. Patients underwent behavioral and treatment assessments at baseline, after 24-week and 1 year follow-up. Behavioral assessment included measures of cognition, fatigue and quality of life. Treatment assessment included measures of satisfaction, persistence and adherence to treatment. Clinical-radiological disease activity and safety were also assessed. Results: Baseline characteristics of patients were similar between groups except for Euro Quality Visual Analogue Scale, being higher in the NTZ group (p = 0.04). Within-group comparisons at the three time points...

Interferon gama versus asma

Hosana Barreto de Oliveira, Francisca; Wanick Sarinho, Silvia (Orientador)
Fonte: Universidade Federal de Pernambuco Publicador: Universidade Federal de Pernambuco
Tipo: Outros
Português
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Objetivo: Revisar a literatura científica acerca do papel do interferon gama (IFN-y) na doença atópica, especificamente asma. Métodos: Pesquisados dados do Medline e Lilacs nos últimos 10 anos. Resultados: Vários autores discutem a importância da relação entre a secreção de IFN-y e o componente atópico per se, por outro lado é questionado se esta citocina tem relação direta com a doença asmática, independente do estado atópico. Foi verificada a existência de várias pesquisas relacionando asma e IFN-y; entretanto, os resultados destas pesquisas se apresentam controversos. Conclusão: Ainda não se chegou a uma conclusão definitiva do verdadeiro mecanismo de atuação desempenhado pelo IFN-y na doença asmática, é indiscutível a importância de novas pesquisas esclarecedoras sobre este assunto

Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase

Branford, S.; Rudzki, Z.; Harper, A.; Grigg, A.; Taylor, K.; Durrant, S.; Arthur, C.; Browett, P.; Schwarer, A.; Ma, D.; Seymour, J.; Bradstock, K.; Joske, D.; Lynch, K.; Gathmann, I.; Hughes, T.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //2003 Português
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We analyzed molecular responses in 55 newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients enrolled in a phase 3 study (the IRIS trial) comparing imatinib to interferon-alfa plus cytarabine (IFN+AraC). BCR-ABL/BCR% levels were measured by real-time quantitative RT-PCR and were significantly lower for the imatinib-treated patients at all time points up to 18 months, P<0.0001. The median levels for imatinib-treated patients continued to decrease and had not reached a plateau by 24 months. A total of 24 IFN+AraC-treated patients crossed over to imatinib. Once imatinib commenced, the median BCR-ABL/BCR% levels in these patients were not significantly different to those on first-line imatinib for the equivalent number of months. The incidence of progression in imatinib-treated patients, defined by hematologic, cytogenetic or quantitative PCR criteria, was significantly higher in the patients who failed to achieve a 1 log reduction by 3 months or a 2 log reduction by 6 months, P=0.002. A total of 49 patients were screened for BCR-ABL kinase domain mutations. Mutations were detected in two imatinib-treated patients who crossed over from IFN+AraC and both lost their imatinib response. In conclusion, first-line imatinib-treated patients had profound reductions in BCR-ABL/BCR%...

Regulation of production of mucosal antibody to pneumococcal protein antigens by T-cell-derived gamma interferon and interleukin-10 in children

Zhang, Q.; Bernatoniene, J.; Bagrade, L.; Paton, J.; Mitchell, T.; Hammerschmidt, S.; Nunez, D.; Finn, A.
Fonte: Amer Soc Microbiology Publicador: Amer Soc Microbiology
Tipo: Artigo de Revista Científica
Publicado em //2006 Português
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Nasopharyngeal tonsils (adenoids) are part of human nasopharynx-associated lymphoid tissue, which may play an important role in local defense against pneumococci. Recent studies with animals have suggested that several pneumococcal proteins, including CbpA and pneumolysin (Ply), may be vaccine candidates. Our recent data obtained with children suggest that antibodies to these proteins may protect against carriage. This study was performed to investigate the regulation of the T-cell-dependent antibody responses to CbpA and pneumolysin by cytokines in adenoidal immune cells from children. Adenoidal mononuclear cells (MNC) were cultured with pneumococcal concentrated culture supernatants (CCS) or recombinant proteins. Cytokine expression profiles in adenoidal MNC after antigen stimulation were analyzed by reverse transcription-PCR, protein array analysis, and an immunoassay, along with an antibody production analysis. The roles, interactions, and cellular sources of the main cytokines identified were evaluated further. Pneumococcal CCS induced production of CbpA- and Ply-specific antibodies in association with several chemokines and cytokines, including gamma interferon (IFN-) and interleukin-10 (IL-10) in MNC. The antibody production correlated well with the concentrations of these two cytokines. Addition of recombinant IFN- or IL-10 enhanced antibody production...

Structural and functional homology between duck and chicken interferon-gamma

Huang, A.; Scougall, C.; Lowenthal, J.; Jilbert, A.; Kotlarski, I.
Fonte: Pergamon-Elsevier Science Ltd Publicador: Pergamon-Elsevier Science Ltd
Tipo: Artigo de Revista Científica
Publicado em //2001 Português
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The Duck interferon gamma (DuIFN-gamma) cDNA was cloned from a phytohaemaglutinin-stimulated duck spleen cDNA library screened using a chicken IFN-gamma (ChIFN-gamma) cDNA probe. The DuIFN-gamma cDNA is 1392 nt long and shows 99% and 80% sequence identity with another cloned DuIFN-gamma cDNA, and with ChIFN-gamma cDNA, respectively. The cDNA contains a 495 bp ORF that encodes a putative 164 amino acid (AA) protein that shares 67% identity with ChIFN-gamma, but only 30-35% identity with mammalian IFN-gamma. The predicted three-dimensional (3D) structures of DuIFN-gamma and ChIFN-gamma are similar when analysed by comparative protein modelling. Culture supernatant collected from COS cells transfected with DuIFN-gamma cDNA was able to activate nitrite secretion from a chicken macrophage cell line (HD11) in a dose-dependent fashion. This activity could not be neutralised by an anti-ChIFN-gamma monoclonal antibody (Mab 85) that was able to neutralise the activity of ChIFN-gamma. Recombinant DuIFN-gamma (rDuIFN-gamma) protein was expressed in E. coli as an N-terminally His-tagged protein and was purified on a nickel affinity column. The eluted protein, which was detected as a approximately 18 kDa band with a purity of >90%, was also detected by Western blot using the anti-ChIFN-gamma monoclonal antibody (Mab 9.1). The rDuIFN-gamma was shown to activate nitrite secretion by HD11 cells in a dose-dependent fashion with a specific activity that was approximately 16-fold lower than a rChIFN-gamma control. Two rabbit antisera raised against rDuIFN-gamma were able to neutralise COS cell-expressed DuIFN-gamma activity; one of these also neutralised ChIFN-gamma activity. These findings indicate that DuIFN-gamma shares structural and functional identity with ChIFN-gamma...

Identification of endometrial genes regulated by early pregnancy progesterone and interferon tau in the ovine uterus

Gray, C.; Abbey, C.; Beremand, P.; Choi, Y.; Farmer, J.; Adelson, D.; Thomas, T.; Bazer, F.; Spencer, T.
Fonte: Soc Study Reproduction Publicador: Soc Study Reproduction
Tipo: Artigo de Revista Científica
Publicado em //2006 Português
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During early pregnancy in ruminants, progesterone (P4) from the corpus luteum and interferon tau (IFNT) from the conceptus act on the endometrium to regulate genes important for uterine receptivity and conceptus growth. The use of the uterine gland knockout (UGKO) ewe has demonstrated the critical role of epithelial secretions in regulation of conceptus survival and growth. A custom ovine cDNA array was used to identify alterations in gene expression of endometria from Day 14 cyclic, pregnant, and UGKO ewes (study 1) and from cyclic ewes treated with P4 or P4 with ZK 136,317 antiprogestin and control proteins or IFNT (study 2). In study 1, expression of 47 genes was more than 2-fold different between Day 14 pregnant and cyclic endometria, whereas 23 genes was different between Day 14 cyclic and UGKO endometria. In study 2, 70 genes were different due to P4 alone, 74 genes were affected by IFNT in a P4-dependent manner, and 180 genes were regulated by IFNT in a P4-independent manner. In each study, an approximately equal number of genes were found to be activated or repressed in each group. Endometrial genes increased by pregnancy and P4 and/or IFNT include B2M, CTSL, CXCL10, G1P3, GRP, IFI27, IFIT1, IFITM3, LGALS15, MX1, POSTN, RSAD2...

Impact of alcohol on hepatitis C virus replication and interferon signaling

McCartney, E.; Beard, M.
Fonte: W J G Press Publicador: W J G Press
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
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Hepatitis C virus (HCV) is one of the main etiological factors responsible for liver disease worldwide. It has been estimated that there are over 170 million people infected with HCV worldwide. Of these infected individuals, approximately 75% will go on to develop a life long necroinflammatory liver disease, which over decades, can result in serious complications, such as cirrhosis and hepatocellular carcinoma. Currently there is no effective vaccine and whilst antiviral therapies have been improved, they are still only effective in approximately 50% of individuals. HCV infection stands as a major cause of global morbidity and suffering, and places a significant burden on health systems. The second highest cause of liver disease in the western world is alcoholic liver disease. Frequently, HCV infected individuals consume alcohol, and the combined effect of HCV and alcohol consumption is deleterious for both liver disease and response to treatment. This review discusses the impact of alcohol metabolism on HCV replication and the negative impact on interferon (IFN)-α treatment, with a particular focus on how alcohol and HCV act synergistically to increase oxidative stress, ultimately leading to exacerbated liver disease and a reduction in the efficacy of IFN-α treatment. A better understanding of the complicated mechanisms at play in hepatocytes infected with HCV and metabolizing alcohol will hopefully provide better treatment options for chronic hepatitis C individuals that consume alcohol.; Erin M. McCartney and Michael R. Beard

Molecular interactions between alcohol, hepatitis C virus and interferon.

McCartney, Erin
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2011 Português
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Hepatitis C virus (HCV) is a significant human pathogen that in many cases, establishes a chronic life long infection of the liver, resulting in progressive liver disease that culminates in the development of cirrhosis and hepatocellular carcinoma (HCC). The only treatment option available for HCV infection is a combination therapy of Interferon-α (IFN-α) and Ribavirin. However, it is only successful in a limited number of patients. There are a number of co-factors that accelerate liver disease in chronic hepatitis C (CHC) and one of the most significant factors is alcohol consumption. Furthermore, alcohol consumption has been shown to reduce the efficacy of IFN-α treatment. Despite these clinical observations, the molecular mechanisms by which alcohol exerts these effects are unknown and remain relatively unexplored. This is largely due to the lack of an appropriate model system to enable studies into the interaction between the HCV life cycle, alcohol metabolism and IFN. To overcome this limitation, we have developed an in vitro cell culture model system that enables Huh-7 cells to metabolise alcohol (ethanol), via the enzyme cytochrome P4502E1 (CYP2E1), while also supporting HCV replication directed from both the HCV replicon and infectious HCV model systems. As such...

Interferon type I responses in primary and secondary infections

Alsharifi, M.; Muellbacher, A.; Regner, M.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
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The mammalian host responds to a microbial infection with a rapid innate immune reaction that is dominated by type I interferon (IFN-I) release. Most cells of vertebrates can respond to microbial attack with IFN-I production, but the cell type responsible for most of the systemic IFN-I release is thought to be plasmacytoid dendritic cells (pDCs). Besides its anti-microbial and especially anti-viral properties IFN-I also exerts a regulatory role on many facets of the sequential adaptive immune response. One of these is being the recently described partial, systemic activation of the vast majority of B and T lymphocytes in mice, irrespective of antigen reactivity. The biological significance of this partial activation of lymphocytes is at present speculative. Secondary infections occurring within a short time span of a primary infection fail to elicit a similar lymphocyte activation response due to a refractory period in systemic IFN-I production. This period of exhaustion in IFN-I responses is associated with an increased susceptibility of the host to secondary infections. The latter correlates with well-established clinical observations of heightened susceptibility of patients to secondary microbial infections after viral episodes.; Mohammed Alsharifi...

Pre-existing strain specific neutralising antibodies abrogates the induction of interferon type I and cytotoxic T cell responses to subsequent homotypic influenza A virus challenge.

Chan, Jennifer
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2013 Português
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Current inactivated influenza vaccines target the generation of influenza-specific antibodies to provide homotypic protection. However, little is known about the effects of annual vaccinations on the immune response during a subsequent influenza A virus infection. Here, we investigated the effect of pre-existing influenza-specific neutralising antibodies on innate and adaptive immunity during secondary infections. We report that the presence of pre-existing antibodies abrogates the induction of interferon type I (IFN-I) responses and cytotoxic T cell responses during subsequent influenza A virus infection. Wild-type mice were vaccinated intravenously with gamma-irradiated A/PR8 [H1N1] (γ-A/PR8) and challenged 3 weeks later with live A/PR8, and splenocytes were analysed 24 hours later for IFN-I mediated lymphocyte activation using fluorescent activated cell sorting. Our data clearly show absence of partial systemic lymphocyte activation and IFN-I responses in vaccinated mice. Furthermore, co-administration of A/PR8-specific sera and live A/PR8 virus abrogated the ability of live virus to induce partial lymphocyte activation, IFN-I responses as well as cytotoxic T cell responses. To test the clinical relevance of this observation, mice were mock or vaccinated with γ-A/PR8 and infected 3 weeks later with sub-lethal dose of A/PR8. These animals were then challenged 3 weeks later with lethal dose of A/PC [H3N2]. Our data clearly illustrate the effect of pre-existing antibodies on the ability of sub-lethal infection to generate cytotoxic T cell mediated heterosubtypic protection. I also investigated whether IFN-I responses are required for the generation of cytotoxic T cell responses in the presence of neutralising immune sera. My data show that addition of exogenous Poly I:C to A/PR8 virus pre-treated with A/PR8-specific sera did not rescue the induction of cytotoxic T cell responses. Thus...

A STUDY OF HOST-CHLAMYDIAL INTERACTIONS MEDIATED BY INTERFERON-GAMMA AND NITRIC OXIDE

Rajaram, Krithika
Fonte: [Bloomington, Ind.] : Indiana University Publicador: [Bloomington, Ind.] : Indiana University
Tipo: Doctoral Dissertation
Português
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Thesis (Ph.D.) - Indiana University, Biology, 2015; The host response towards chlamydial infection mobilizes elements of both innate and adaptive immunity, culminating in the production of the Th1 cytokine interferon-gamma (IFN-γ). IFN-γ induces a variety of anti-chlamydial programs, many of which are unique to either humans or mice. Consequently, the human pathogen Chlamydia trachomatis and its near-identical murine relative C. muridarum have evolved to survive and cause disease in their respective hosts. Understanding the mechanisms that contribute to chlamydial niche specificity will facilitate the creation of improved mouse models for the study of human chlamydial disease. To this end, we examined a small chlamydial genomic region of extreme divergence called the Plasticity Zone (PZ) in C. muridarum for its alleged roles in host specificity and virulence. Using a newly adapted reverse genetic technique, we determined that much of the PZ is in fact dispensable in the murine genital tract. We concomitantly embarked on a screen for C. muridarum mutants that were no longer resistant to IFN-γ and uncovered a gain-of-function mutation in an orf outside the PZ that led to dramatic attenuation in mice. IFN-γ is secreted by multiple cell types including macrophages...

Hemangioma Gigante na Criança — Tratamento com Interferon Alfa 2A — Um Caso Clínico

Agostinho, Margarida; Moreno, Ana; Melo, A. Sá e; Barroso, A.; Baptista, A. Poiares
Fonte: Sociedade Portuguesa de Pediatria Publicador: Sociedade Portuguesa de Pediatria
Formato: application/pdf
Publicado em 26/09/2014 Português
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O hemangioma é uma das malformações congénitas mais comuns na infância, habitualmente benigna e de involução expontânea.Em casos raros,pelo seu volume ou pela sua localização em estruturas vitais, pode causar graves problemas e ser de dificil controle.Os autores apresentam o caso clínico de uma criança do sexo feminino, com um hemangioma gigante localizado no hemitórax esquerdo, braço eantebraço esquerdo, que pela sua grande extensão e volume condionava uma insuficiência cardíaca de alto débito, com deficiente crescimento estatoponderai.A gravidade da situação, a ausência de resposta aos 2 ciclos de prednisolona (4 mg/kg/d) e o insucesso da embolização realizada por cateterismocardíaco, levaram à medicação com interferon a-2A (3 milhões de unidades por m2 de superfície corporal, em injecção subcutânea diária). Após o iníciodesta terapêutica, que foi mantida durante um ano, assistiu-se a uma redução rápida e progressiva da massa angiomatosa, com desaparecimento dainsuficiência cardíaca e pronta recuperação do crescimento. À excepção de neutropenia transitória, que não se associou a qualquer infecção, não seregistaram outros efeitos secundários. Actualmente a criança com 3,5 anos de idade...

CXCL16 regulates cell-mediated immunity to Salmonella enterica serovar Enteritidis via promotion of gamma interferon production

Fahy, O.; Townley, S.; McColl, S.
Fonte: Amer Soc Microbiology Publicador: Amer Soc Microbiology
Tipo: Artigo de Revista Científica
Publicado em //2006 Português
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CXCL16 is a recently discovered multifaceted chemokine that has been shown not only to recruit activated T lymphocytes but also to play a direct role in the binding and phagocytosis of bacteria by professional antigen-presenting cells. In this study, we investigated the role of CXCL16 in vivo in the regulation of the immune response using a murine model of Salmonella enterica serovar Enteritidis infection. The expression of CXCL16 was strongly upregulated in the spleens and livers of animals developing an immune response to a primary acute infection but not in the Peyer's patches. Animals developing a secondary response after reexposure to the bacteria displayed a similar pattern of expression. During the primary response, prior treatment with neutralizing antibodies to CXCL16 induced a significant increase in bacterial burden in the spleen and liver. The production of gamma interferon (IFN-γ) by the lymphocytes in the spleen was decreased by anti-CXCL16 treatment. In comparison, during the secondary response, anti-CXCL16 treatment also significantly increased bacterial burden in both the spleen and liver but had no effect on IFN-γ production. No role was found for CXCL16 in the production of antibody against SefA, a major surface antigen of S. enteritidis. Together...

Development of primary invasive pneumococcal disease caused by serotype 1 pneumococci is driven by early increased type I interferon response in the lung

Hughes, C.E.; Harvey, R.M.; Plumptre, C.D.; Paton, J.C.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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The pneumococcus is the world's foremost respiratory pathogen, but the mechanisms allowing this pathogen to proceed from initial asymptomatic colonization to invasive disease are poorly understood. We have examined the early stages of invasive pneumococcal disease (IPD) by comparing host transcriptional responses to an invasive strain and a noninvasive strain of serotype 1 Streptococcus pneumoniae in the mouse lung. While the two strains were present in equal numbers in the lung 6 h after intranasal challenge, only the invasive strain (strain 1861) had invaded the pleural cavity at that time point; this correlated with subsequent development of bacteremia in mice challenged with strain 1861 but not the noninvasive strain (strain 1). Progression beyond the lung was associated with stronger induction of the type I interferon (IFN-I) response in the lung at 6 h. Suppression of the IFN-I response through administration of neutralizing antibody to IFNAR1 (the receptor for type I interferons) led to significantly reduced invasion of the pleural cavity by strain 1861 at 6 h postchallenge. Our data suggest that strong induction of the IFN-I response is a key factor in early progression of invasive serotype 1 strain 1861 beyond the lung during development of IPD.; Catherine E. Hughes...

Us3 disrupts PML nuclear bodies through its interaction with KLHL21 to promote viral gene transcription in interferon-exposed cells

Jung, Masany
Fonte: Quens University Publicador: Quens University
Tipo: Tese de Doutorado
Português
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Us3, a serine/threonine kinase encoded by all alphaherpesviruses, plays diverse roles during virus infection. Recently, work done in our laboratory determined that Us3 orthologues from herpes simplex type 2 (HSV-2) and pseudorabies virus (PRV) are capable of disrupting promyelocytic leukaemia (PML) protein nuclear bodies (-NBs). PML-NBs are discrete, dynamic nuclear bodies named for PML, their essential structural component and one that plays a key role in diverse cellular processes, including transcriptional regulation, apoptosis, and cellular antiviral defense. In infected cells, PML-NBs exert transcriptional silencing on the viral genome to prevent viral gene expression and virus replication. Based on this finding, my studies were aimed to understand the mechanism and physiological function of Us3-mediated PML-NB disruption. The degradation of one or more cellular proteins seems necessary for this Us3 activity, as the proteasome inhibitor, MG132, dramatically reduced Us3-mediated PML-NB disruption. The target of this proteasome activity is not likely PML protein, as Us3 expression did not lead to detectable PML protein degradation. Nonetheless, the involvement of proteasome activity suggests that Us3 may utilize the host ubiquitylation pathway to disrupt PML-NBs. Supporting this hypothesis...