La fibrosis pulmonar es una enfermedad del parénquima pulmonar que cursa generalmente de forma le... more La fibrosis pulmonar es una enfermedad del parénquima pulmonar que cursa generalmente de forma lenta y progresiva. Puede asociarse a enfermedades inmunológicas como, por ejemplo, la artritis reumatoide. Guarda muy poca relación con la psoriasis y/o la artritis psoriásica. En otros casos, el inicio de la enfermedad está, en el contacto repetido con una sustancia que provoca una alveolitis alérgica extrínseca y que, si se mantiene en el tiempo, puede evolucionar a una fibrosis ya establecida. El factor de necrosis tumoral (TNF) es una citocina proinflamatoria que existe en forma circulante y en forma transmembranaria y que, como cualquier citocina, está implicada en funciones de defensa del huésped 1. Los fármacos antagonistas del TNF han demostrado su eficacia y seguridad en enfermedades como la artritis reumatoide y la artritis psoriásica 2,3. Actualmente hay en el mercado 2 fármacos anti-TNF útiles para estas 2 enfermedades reumatológicas: una proteína de fusión dimérica, compuesta por la porción extracelular del
Rheumatoid arthritis (RA) is a chronic autoimmune disease with destructive lesions of peripheral ... more Rheumatoid arthritis (RA) is a chronic autoimmune disease with destructive lesions of peripheral joints. It have been shown that IL-1, IL-6 and TNF-α are the most important inflammatory cytokines in rheumatoid synovium. The first anti-TNF drug approved for clinical use was infliximab (Inx), unfortunately, 30% of the patients are primary non-responders. The aim of our research was to examine the profile of IL-6 and TNF-α in RF-positive positive patients with rheumatoid arthritis during infliximab treatment. Materials and methods. The study included 28 patients (22 females, 6 males) with RFpositive variant of RA, mean age of 42,6 ± 2,8 years, duration of a disease is 7,2 ± 1,4 years. All patients received combined therapy with methotrexate (MT-12,5-15 mg) and Inx which was injected at single dose of 3 mg/kg intravenously, followed by administration 2 and 6 weeks later, and repeated every 8 weeks (6 infusions). Efficiency of the therapy was estimated according to DAS28 4V Index and improvement criteria of EULAR. Regular examination of patients included dynamics TNF-α and IL-6 of serum and supernatants which was determined in ELISA, the quantity of lymphocytes expressing receptors to TNF-α (CD120a). Results. Two groups of patients have been estimated depending on EULAR improvement criteria of therapy after 6th infusions: I group with a good response and II group with moderate response or no response. Conclusion. Non-responders have initial increased IL-6 and TNF-α in serum, it was initial increased PHAstimulated production of TNF-α and IL-6 by PMBC and CD120a-lymphocytes not determined in a blood.
effective in the treatment of severe CDAD. However, this cohort has a high mortality and careful ... more effective in the treatment of severe CDAD. However, this cohort has a high mortality and careful selection of patients is essential. We would advocate the use of IVIG for selected cases of CDAD when surgery is not possible and all other treatment options have been exhausted. T2056 Characterization of a Two-Component Regulatory System in a Type IV Pili of Etec Bharani Pandrangi, Oscar Gomez Enterotoxigenic E. coli (ETEC) is a leading cause of diarrhea in developing countries and an important cause of traveler's diarrhea. ETEC colonization is believed to be mediated by pili. Longus is one of the most prevalent type IV pili described in ETEC and is believed to be involved in the colonization and pathogenesis of ETEC. Longus is > 20 μm in length, plasmid-encoded, and consists of a polymerized 22 kDa structural subunit. Gene variation studies showed that lngA is grouped into three distinctive phylogenetic groups. Longus requires 16 genes for its expression which are carried in a 14 Kb DNA cluster. A regulatory region has been identified in the Longus DNA cluster based on homology analysis. The Longus regulatory region is composed of two genes, lngR and lngS, that share homology with two-component global regulators of virulence, including the toxin co-regulated pilin (TCP) regulators of Vibrio cholerae and the bundle-forming pilin (BFP) regulators of EPEC. LngS has homology to the Ara C family of regulators and LngR to the PapB family. LngS putative protein contains a helix-turn-helix motif, believed to bind DNA sequences at promotor regions, and shares similarity to other regulatory proteins. The goal of this study is to characterize the lngR and lngS genes at the DNA and protein levels and to develop the tools to analyze the potential role of these genes in global regulation of ETEC virulence. LngA positive ETEC strains were selected from our collection for DNA sequencing studies. Primers were designed for PCR amplification, cloning, and sequencing of lngR, lngS and Longus promoter regions. DNA sequencing analysis was performed based on multiple sequence alignments of these genes using GCG, NCBI and EXPASY software programs. The lngR gene had a single nucleotide difference among human ETECs and 9 nucleotide differences with respect to an animal derived ETEC. At the protein level no residue changes were found in LngR among all human ETECs. In contrast, 7 residue changes were found in the LngR derived from the animal strain. DNA sequencing of lngS had 37 nucleotide differences with respect to the E9034A published sequence which resulted in 17 residue changes. 7 of the 17 residue changes were observed in a single animal-derived ETEC. LngS genes produced multiple different proteins and included synonymous and non-synonymous mutations. The lngR gene is conserved among human ETEC isolates. LngS is highly variable among animal and human ETECs, suggesting that differences in the Longus gene regulation are likely mediated by LngS.
La fibrosis pulmonar es una enfermedad del parénquima pulmonar que cursa generalmente de forma le... more La fibrosis pulmonar es una enfermedad del parénquima pulmonar que cursa generalmente de forma lenta y progresiva. Puede asociarse a enfermedades inmunológicas como, por ejemplo, la artritis reumatoide. Guarda muy poca relación con la psoriasis y/o la artritis psoriásica. En otros casos, el inicio de la enfermedad está, en el contacto repetido con una sustancia que provoca una alveolitis alérgica extrínseca y que, si se mantiene en el tiempo, puede evolucionar a una fibrosis ya establecida. El factor de necrosis tumoral (TNF) es una citocina proinflamatoria que existe en forma circulante y en forma transmembranaria y que, como cualquier citocina, está implicada en funciones de defensa del huésped 1. Los fármacos antagonistas del TNF han demostrado su eficacia y seguridad en enfermedades como la artritis reumatoide y la artritis psoriásica 2,3. Actualmente hay en el mercado 2 fármacos anti-TNF útiles para estas 2 enfermedades reumatológicas: una proteína de fusión dimérica, compuesta por la porción extracelular del
Rheumatoid arthritis (RA) is a chronic autoimmune disease with destructive lesions of peripheral ... more Rheumatoid arthritis (RA) is a chronic autoimmune disease with destructive lesions of peripheral joints. It have been shown that IL-1, IL-6 and TNF-α are the most important inflammatory cytokines in rheumatoid synovium. The first anti-TNF drug approved for clinical use was infliximab (Inx), unfortunately, 30% of the patients are primary non-responders. The aim of our research was to examine the profile of IL-6 and TNF-α in RF-positive positive patients with rheumatoid arthritis during infliximab treatment. Materials and methods. The study included 28 patients (22 females, 6 males) with RFpositive variant of RA, mean age of 42,6 ± 2,8 years, duration of a disease is 7,2 ± 1,4 years. All patients received combined therapy with methotrexate (MT-12,5-15 mg) and Inx which was injected at single dose of 3 mg/kg intravenously, followed by administration 2 and 6 weeks later, and repeated every 8 weeks (6 infusions). Efficiency of the therapy was estimated according to DAS28 4V Index and improvement criteria of EULAR. Regular examination of patients included dynamics TNF-α and IL-6 of serum and supernatants which was determined in ELISA, the quantity of lymphocytes expressing receptors to TNF-α (CD120a). Results. Two groups of patients have been estimated depending on EULAR improvement criteria of therapy after 6th infusions: I group with a good response and II group with moderate response or no response. Conclusion. Non-responders have initial increased IL-6 and TNF-α in serum, it was initial increased PHAstimulated production of TNF-α and IL-6 by PMBC and CD120a-lymphocytes not determined in a blood.
effective in the treatment of severe CDAD. However, this cohort has a high mortality and careful ... more effective in the treatment of severe CDAD. However, this cohort has a high mortality and careful selection of patients is essential. We would advocate the use of IVIG for selected cases of CDAD when surgery is not possible and all other treatment options have been exhausted. T2056 Characterization of a Two-Component Regulatory System in a Type IV Pili of Etec Bharani Pandrangi, Oscar Gomez Enterotoxigenic E. coli (ETEC) is a leading cause of diarrhea in developing countries and an important cause of traveler's diarrhea. ETEC colonization is believed to be mediated by pili. Longus is one of the most prevalent type IV pili described in ETEC and is believed to be involved in the colonization and pathogenesis of ETEC. Longus is > 20 μm in length, plasmid-encoded, and consists of a polymerized 22 kDa structural subunit. Gene variation studies showed that lngA is grouped into three distinctive phylogenetic groups. Longus requires 16 genes for its expression which are carried in a 14 Kb DNA cluster. A regulatory region has been identified in the Longus DNA cluster based on homology analysis. The Longus regulatory region is composed of two genes, lngR and lngS, that share homology with two-component global regulators of virulence, including the toxin co-regulated pilin (TCP) regulators of Vibrio cholerae and the bundle-forming pilin (BFP) regulators of EPEC. LngS has homology to the Ara C family of regulators and LngR to the PapB family. LngS putative protein contains a helix-turn-helix motif, believed to bind DNA sequences at promotor regions, and shares similarity to other regulatory proteins. The goal of this study is to characterize the lngR and lngS genes at the DNA and protein levels and to develop the tools to analyze the potential role of these genes in global regulation of ETEC virulence. LngA positive ETEC strains were selected from our collection for DNA sequencing studies. Primers were designed for PCR amplification, cloning, and sequencing of lngR, lngS and Longus promoter regions. DNA sequencing analysis was performed based on multiple sequence alignments of these genes using GCG, NCBI and EXPASY software programs. The lngR gene had a single nucleotide difference among human ETECs and 9 nucleotide differences with respect to an animal derived ETEC. At the protein level no residue changes were found in LngR among all human ETECs. In contrast, 7 residue changes were found in the LngR derived from the animal strain. DNA sequencing of lngS had 37 nucleotide differences with respect to the E9034A published sequence which resulted in 17 residue changes. 7 of the 17 residue changes were observed in a single animal-derived ETEC. LngS genes produced multiple different proteins and included synonymous and non-synonymous mutations. The lngR gene is conserved among human ETEC isolates. LngS is highly variable among animal and human ETECs, suggesting that differences in the Longus gene regulation are likely mediated by LngS.
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