RESUMO
We herein describe a rare case of low-grade endobronchial tumor that exhibited two distinct features of typical carcinoid and acinic cell carcinoma (ACC) by immunohistochemical and ultrastructure study. ACC was suspected on transbronchial biopsy. The resected specimen showed that the tumor surface comprised an acinic cell component (40% of the tumor), and the central area comprised typical carcinoid (60% of the tumor). The acinic cell component was positive for chromogranin A, synaptophysin and alpha-1-antichymotrypsin. Additionally, this component showed focal apical membranous staining for DOG1 and weak positivity for BCL10 and SOX10. Conversely, the carcinoid component was negative for all proteins except for chromogranin A and synaptophysin. Electron microscopy indicated zymogen-type granules (600-800 nm in diameter) in the acinic cell component, whereas neuroendocrine-type granules (200-300 nm in diameter) were observed in the carcinoid component. Nuclear NR4A3 immunostaining, which is highly specific for ACC of the salivary gland, was negative in this case. We conclude that the pulmonary carcinoid tumor with true zymogen-type granules could be seen but showed superficial similarities to ACC based on negative nuclear staining for NR4A3. Pulmonary carcinoids encompass a wide morphological spectrum and may exhibit prominent acinic cell differentiation.
Assuntos
Biomarcadores Tumorais/análise , Tumor Carcinoide/diagnóstico por imagem , Carcinoma de Células Acinares/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Idoso , Tumor Carcinoide/patologia , Carcinoma de Células Acinares/patologia , Diferenciação Celular , Feminino , Humanos , Imuno-Histoquímica , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/patologia , Microscopia Eletrônica , Vesículas Secretórias/patologia , Tomografia Computadorizada por Raios XRESUMO
Amphidinol 3 (AM3) is an anti-fungal polyene extracted from a marine dinoflagellate. Here, we examined the ion channel activity and membrane-embedded structure of AM3 using a lipid bilayer method and atomic force microscopy (AFM). AM3 exhibited large-conductance (~1 nS) and non-selective single-channel activity only when sterols were present in the membrane leaflet of the AM3-added side. The variable conductance suggests the formation of a multimeric barrel-stave pore. At high AM3 concentrations, giant-conductance "jumbo" channels (~40 nS) emerged. AFM revealed a thicker raft-like membrane phase with the appearance of a wrinkled surface, in which phase pores (diameter: ~10 nm) were observed. The flip-flop of ergosterol occurred only after the appearance of the jumbo channel, indicating that the jumbo channel induced a continuity between the outer and inner leaflets of the membrane: a feature characteristic of toroidal-like pores. Thus, AM3 forms different types of sterol-aided polymorphic channels in a concentration dependent manner.
Assuntos
Alcenos/química , Membrana Celular/química , Piranos/química , Esteróis/química , Fenômenos Eletrofisiológicos , Ergosterol/química , Bicamadas Lipídicas/química , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/metabolismo , Microscopia de Força Atômica , Estrutura MolecularRESUMO
Extracellular signal-regulated kinase (ERK) signalling plays a central role in various biological processes, including cell migration, but it remains unknown what factors directly regulate the strength and duration of ERK activation. We found that, among the B56 family of protein phosphatase 2A (PP2A) regulatory subunits, B56γ1 suppressed EGF-induced cell migration on collagen, bound to phosphorylated-ERK, and dephosphorylated ERK, whereas B56α1 and B56ß1 did not. B56γ1 was immunolocalized in nuclei. The IER3 protein was immediately highly expressed in response to costimulation of cells with EGF and collagen. Knockdown of IER3 inhibited cell migration and enhanced dephosphorylation of ERK. Analysis of the time course of PP2A-B56γ1 activity following the costimulation showed an immediate loss of phosphatase activity, followed by a rapid increase in activity, and this activity then remained at a stable level that was lower than the original level. Our results indicate that the strength and duration of the nuclear ERK activation signal that is initially induced by ERK kinase (MEK) are determined at least in part by modulation of the phosphatase activity of PP2A-B56γ1 through two independent pathways.
Assuntos
Movimento Celular , Núcleo Celular/enzimologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína Fosfatase 2/metabolismo , Células 3T3 , Sequência de Aminoácidos , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Colágeno/farmacologia , Ativação Enzimática/efeitos dos fármacos , Fator de Crescimento Epidérmico/farmacologia , Humanos , Cinética , Proteínas de Membrana/metabolismo , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Dados de Sequência Molecular , Fosforilação/efeitos dos fármacos , Proteína Fosfatase 2/química , Transporte Proteico/efeitos dos fármacosRESUMO
Actinomyces viscosus has been suggested to be associated with periodontal disease. However, the pathogenicity of this bacterium is not known. In this study, we examined inflammation-inducing activity by A. viscosus. Whole cells and a lipophilic fraction of A. viscosus ATCC19246 induced production of interleukin-8 and tumor necrosis factor alpha from both human oral epithelial cells and human monocytoid cells. This cytokine production was blocked by lipoprotein lipase treatment of the lipophilic fraction. In addition, anti-Toll-like receptor 2 antibody blocked the cytokine production. These results suggest that lipoprotein of A. viscosus triggers inflammatory responses in periodontitis by activation of Toll-like receptor 2.
Assuntos
Actinomyces viscosus/imunologia , Gengiva/imunologia , Lipoproteínas/imunologia , Receptor 2 Toll-Like/imunologia , Actinomyces viscosus/química , Actinomicose/imunologia , Actinomicose/microbiologia , Análise de Variância , Proteínas de Bactérias/imunologia , Citocinas/imunologia , Células Epiteliais/citologia , Células Epiteliais/imunologia , Gengiva/citologia , Doenças da Gengiva/imunologia , Doenças da Gengiva/microbiologia , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Inflamação/imunologia , Macrófagos/citologia , Macrófagos/imunologiaRESUMO
Most trichomes on the surface of cucumber (Cucumis sativus L.) cotyledons consist of three cells. We previously showed that continuous UV-B (290-320 nm) irradiation induces rapid cellular expansion and the accumulation of polyphenolic compounds, possibly stress lignin, in epidermal cells around these trichomes.(1)) To examine the mechanism of the UV-B-induced cellular expansion and to determine which step is stimulated by UV-B irradiation in the lignin synthesis pathway, we investigated relative DNA contents in epidermal cells, including trichomes, and enzyme activity and gene expression in the phenylpropanoid pathway. UV-B irradiation increased the ploidy level over 15 days, specifically in the epidermal cells surrounding trichomes, but not in the other epidermal cells or trichomes. In epidermal cells surrounding trichomes, UV-B irradiation induced peroxidase (POX) activity from days 7 to 15. In cotyledons, UV-B exposure induced CS-POX1 and CS-POX3 gene expression within 2 days, and it also induced two other enzymes in the phenylpropanoid pathway, sinapyl alcohol dehydrogenase and coniferyl alcohol dehydrogenase, from days 9 to 11. Thus, exposure to UV-B induces expansion, endoreduplication, POX activity, and the accumulation of polyphenolic compounds in epidermal cells surrounding the trichomes of cucumber cotyledons. Because polyphenolic compounds such as lignin absorb UV-B, our data indicate a physiological protective mechanism against UV-B irradiation in cucumber.